CTSI Annual Pilot Awards to Improve the Conduct of Research

An Open Proposal Opportunity

Printable Proposal Content

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Overcoming hurdles to patient-centered outcomes research

Proposal Status: 

The Patient Centered Outcomes Research Institute is charged with facilitating informed choice by funding initiatives that create condition-specific registries designed to provide information necessary for patients to understand risks and expected benefits in terms of meaningful outcomes. Traditionally, registries require hiring personnel, not directly involved in the care of patients, to distribute surveys, review charts, fill in forms, and enter data into an offsite registry. We employed a method to generate registry data for joint replacement and spine surgery that uses existing data. All hospitals, clinics and emergency departments use ICD-9 diagnosis, procedure and CPT codes to describe every patient encounter. Unlike the electronic health record, these data are stored in a uniform format. The integrated claims repository employs an ontology, which is a set of terms commonly used by patients and physicians to describe patient demographics, etiology, comorbidities, procedures and outcomes such as complications, readmission and reoperation rates. The ontology script, adaptable to any field of medicine, includes parameter names and codes associate with the parameters. A program reads the script and generates the program that creates the integrated claims repository. The University of California Office of the President recently approved funding create a spine registry by replicating the integrated claims repository at the other UC medical school campuses. The UCSF Committee on Human Research (CHR) approved the project and Notice of Intent to Rely (NOITR) is streamlining approval at the other campuses. The ontology has also been adapted to query national and statewide inpatient and ambulatory datasets.

The first aim of this proposalis to establish a CTSI clinical registry consultancy to help researchers create ontologies to define integrated claims repositories and condition-specific registries. This consultancy will enable collaborators in other clinical fields to create preliminary data for PCORI grants. Steps for generating these data: 1) develop and validate ontology definitions through chart review and queries of the University HealthSystem Consortium database. 2) Define inclusion and exclusion criteria and parameters for the registry. 3) Gain CHR approval with NOITR. 4) Implement the integrated claims repository. 5) Create reports. 6) Replicate this work at other campuses and compile collaborative registry data. 7) Generate state- and nationwide statistics for the condition. Metrics of success are the number of publications and grant submissions arising from claims repositories established in other fields of medicine. This model will become self-sustaining through consultant fees and grant collaborations.

Regulatory issues being addressed include: Determining whether the registry activity is research or a quality improvement activity. What activities require patient consent and HIPAA authorization? What options are available for Business Associate Agreements? What are the concerns of the Privacy Office? What computer security controls are needed? How can data be added or extracted from the electronic health record? What are the restrictions when using cost data? How do you protect sensitive patient information when using iPads or iPhones for data collection?

The second aim of this proposal is to work closely with the CHR and Regulatory and Knowledge Support Director to 1) gain approval to set up integrated claims repositories at the 5 UC campuses, and 2) develop libraries of CHR and consent form templates, business associate agreements, and other regulatory documents. By the end of the pilot, a library of template regulatory documents will be created that will enable student and post-graduate trainees to produce notable results during a well-planned research rotation.

Budget: $70,000. The budget will provide 20% time to refine regulatory documents and establish the registry model beyond spine surgery, and support in the CHR and RKS offices to develop and maintain document template library.

Collaborators: Elizabeth Boyd, John Heldens

Commenting is closed.

Action Research Program

Proposal Status: 

Rationale The Program in Implementation Science has created a series of courses within the Training in Clinical Research Program that are designed to meet the didactic training needs of fellows and junior faculty, but lacks an experiential component.  To be effective, implementation research must accommodate the unique culture and context that define specific health care settings and communities.  An “Action Research” Program can help meet this need—which involves partnering with health care providers to improve their own practices, which in turn will enhance their working environment.  Action research’s strength lies in its focus on generating solutions to practical problems and its ability to empower health care providers, by getting them to engage with research and the subsequent development or implementation activities.  We propose an action research program to achieve at least 3 broad goals:


1. To design innovative strategies to improve health care delivery or public/community health in real-time in San Francisco by capitalizing on the experience and skills of an interdisciplinary team of UCSF implementation scientists... the goal of which is to improve health and care delivery in targeted settings using strategies that are designed to be patient-centered and to reduce total health care costs.


2. To provide a hands-on training and implementation experience for students, residents and fellows by involving them in a real-world project through all stages of development... the goal of which is to attract/encourage students to pursue careers committed to improving health care delivery, system redesign and community health programs.


3. To design an action research program that can be self-sustaining through reimbursements from stakeholder organizations and delivery systems who directly benefit financially from the impact of the action research program.



We request pilot funds for 1 year to develop and implement this program at UCSF.  It will consist broadly of 8 steps that culminate with the initial launch of a delivery system intervention. 

Step 1. Select a Partner with a “Hot Spot”. Hot spots are problem areas in clinical operations, quality or health outcomes that are identified by stakeholders (such as payors, administrators, providers or patients) as priority areas for intervention.  In our first cycle, we will focus on UCSF Medical Center ambulatory practices.  To identify potential partners, we will invite practice chiefs and administrative directors of these practices to submit brief, 1-page descriptions of Hot Spots in their practice that they would like the action research program team to help them intervene on.  Key criteria will include feasibilty of measuring and intervening on Hot Spot, engagement of clinic providers/staff, learner access to relevant data, staff, patients and providers, and degree to which addressing hot spot will help improve quality, reduce health care costs and enhance the patient experience.

Step 2.  Assemble Action Team.  Advertise volunteer/training opportunities to students and residents in medicine, pharmacy, nursing and dentistry.  Commitment of 2-4 hours per week for 4-6 months is required.  Limit to 6-8 students.  Identify key content/strategy experts from UCSF faculty and partners.

Step 3. Characterize Hot Spot with existing data sources.  Further characterize with administrative and/or medical record data to examine frequency, distribution, variability and predictors of the key process or outcome that represents the Hot Spot.

Step 4.  Conduct Literature Review of Hot Spot.  This will be performed by a combination of faculty and students.  Medical students will apply some of the principles taught in their EEBM (Epidemiology and Evidence Based Medicine) classes.

Step 5. Convene Launch Meeting and Design Workshop.  This will be a 1 or 2 day retreat in which the partner clinic (and staff) are brought together with the faculty and students on the Action Team.  The goal of the meeting will be to create a timetable with specific activities benchmarks for completing the project in a 4-6 month time frame.

Step 6. Conduct & Analyze Formative Research.  Interviews and observations will be performed to gain a greater understanding of the patient, provider, staff and system-level factors that contribute to the Hot Spot being investigated.  With close guidance from faculty, students will be charged with collecting and analyzing this data.

Step 7. Create Alpha-Version of Intervention Approach.  Combine data inputs from the literature review, the quantitative analysis of administrative/EMR data, and the formative research findings to design an intervention approach. 

Step 8. Launch First Iteration (Beta-Version) of Intervention; Collect Process Data


Criteria and metrics for success

  1. Submission of Hot Spot proposals from multiple clinics—shows interest/need for service.
  2. Requests to participate from multiple students/residents—shows interest/appeal to trainees.
  3. Implementation of intervention that has a significant impact (>10-20% change from baseline) on Hot Spot measure.
  4. Explicit plan for continued monitoring and refinement of intervention by participating clinic.


Total Budget: $70,904

Salary support for principal faculty and part-time research assistant.


Collaborators: Ralph Gonzales (Medicine); Margaret Handley (Epidemiology & Biostatistics); Sara Ackerman (Medicine); Joshua Adler (Chief Medical Officer; UCSF Medical Center)

Commenting is closed.

Extending Direct-to-Participant Recruitment on the Internet with Effective Online Self-Screening Eligibility Surveys

Proposal Status: 

Rationale: Developing efficient and effective methods to recruit and screen participants for clinical research remains a major challenge for clinical discovery.

Traditional recruitment methods often involve building up large multi-site research networks and implementing cumbersome and resource-intensive screening processes that incur high fixed startup costs and delay timetables. These challenges hinder the scale and scope of otherwise worthy research questions and delay the production and application of clinical evidence to guide pressing clinical practice and policy questions.

Newer approaches have been developed to harness the broad reach, focused geographic targeting, and powerful economies of scale and efficiencies that are possible using direct-to-participant Internet recruitment. For example, we have recently implemented two studies, the WebTIA Project (completed) and a recruitment site for a stem cell trial for stroke (http://stemcellstudy.ucsf.edu, ongoing), and the CTSI’s Participant Recruitment Service has been working on delivering similar methods as a core service to accelerate the conduct of clinical research.

However, current Internet-based direct-to-participant methods have often been focused on the first step of identifying and targeting potential participants and matching them to potential studies, but less on how to effectively manage the volume of inquiries that these Internet-based efforts can generate.

For our most recent study recruitment website, we used an extensive online prescreening and eligibility process with participant-facing questionnaires to guide potential participants to self-report key eligibility-related questions. An automated algorithm then classified responses as concordant, discordant, or neutral for study eligibility in a way that accounted for differences in health literacy and for uncertainty in certain types of self-reported health information. This system allowed us to extend the capacity of research coordinators by prioritizing and focusing enrollment efforts on those individuals that may be most likely to meet final eligibility criteria and in ways that could be designed to prepopulate a study’s enrollment database after verification.

We believe that extending the Internet-based recruitment core currently under development through the CTSI Participant Recruitment Service with a robust and scalable pre-screening process would enhance the usefulness and potential for this recruitment method and would be the next key step toward the goal integrating pre-screening and enrollment activities with post-enrollment online clinical research tools.


We propose to extend the Participant Recruitment Service’s Internet-based recruitment core by adding a self-reported pre-screening platform for a pilot study that provides:

1)    The ability to classify pre-screening responses as concordant, discordant, or neutral for study eligibility in a way that accounts for differences in health literacy and for uncertainty in self-reported health information.

2)    Dynamic online reports and readouts for study coordinators to help prioritize potential for eligibility validation and enrollment.

3)    Integration with post-enrollment research system to allowed for moving validated data elements to a study database.

Criteria and Metrics for Success:

Pilot Website Launch

# website hits

# primary prescreening forms initiated/completed

# who pass primary prescreening

# secondary prescreening forms initiated/completes

# enrolled from this source

% of overall recruitment goal

% prescreened/secondary screened/enrolled meeting diversity criteria

cost per enrollee

Total Budget: $33,810

$33,810 (12 months) - 5% FTE for PI; 7.5% FTE of the PRS Technical Recruitment Specialist; 5% FTE of the Marketing and Outreach Coordinator; Website Design and Programming


Anthony Kim, Neurology

Nariman Nasser, Director CTSI Participant Recruitment Service

Commenting is closed.

RandomizationCentral.org: an open-source, web based randomization portal to support RCTs for the global research community

Proposal Status: 

Rationale: An effective randomization system is crucial to the design, conduct, and analysis of any randomized controlled trial (RCT).  Despite the apparent ease of flipping a coin (either literally or with a computer algorithm), designing a reliable randomization system that meets the design, statistical and logistical requirements for real-world use in an RCT is a major challenge.  Multicenter critical care studies, for example, typically require extremely rapid access to a centralized system (24 hours/day), for randomization of time-sensitive interventions, while maintaining blinding and balanced recruitment between treatment arms and entry criteria strata.  Large scale NIH and industry funded trials can invest in designing, building and hosting web-based randomization systems that accomplish these goals, but the costs of doing this are prohibitive for smaller trials with more constrained budgets. The design and implementation of a state-of-the-art randomization system that could be made available to the global research community at very low cost would facilitate the conduct of properly designed and blinded RCTs and remove an important barrier to the conduct of interventional research.

One commentor gave us 2 web sites that were already set up to do what we had proposed. Thanks for the referrals. We were not aware of them before and had not found them on our search.

These are indeed usable platforms for randomizing patients in clinical trials. I have tested them out and they provide just the system that we were proposing to create. The prices are not unreasonable either: one system is better for smaller studies (http://www.randomizer.at)(start up cost is $600 for first 50 enrollees and then $5/ additional enrollee; the other system (http://www.randomize.net/) has a flat fee of $2500 and is independent of the size of the enrollment (good for large studies).

It would be a good idea if the CTSI could post these web addresses on the CTSI web site resource page to alert investigators that there are inexpensive randomizer sites available for their studies.

We will withdraw our proposal.

Commenting is closed.

Internet Based Solution for Enhancing Patient Recruitment

Proposal Status: 


Research that requires real-time recruitment in emergency department/acute care setting is labor intensive and costly. Relying on clinicians leads to low recruitment. Clinicians in busy acute care settings often find it challenging to screen and enroll patients for research studies while maintaining clinical priorities. This is further complicated by several different ongoing studies (often led by research faculty from outside departments) and it remains challenging to  keep clinicians current on the various eligibility criteria due to variable work hours.  While most emergency departments use the traditional approach of having a research assistant who screens for eligibility based on physician/resident notification, this approach has inherent problems: the cost and/or availability of research assistant coverage 24/7, variability among physicians in their notification of research assistants about eligible subjects, and the resulting patient ineligibility due to lack of timely screening. We believe that some of these drawbacks of the traditional approach could be overcome by use of an automated electronic screening tool.


We propose to examine the utility of an automated electronic clinical research screening technology to assess the comparative effectiveness of this method to the traditional system of research associates. This technology is currently installed at the University of California, San Francisco Medical Center Emergency Department (UCSF). We will utilize this technology in the setting of an ongoing NINDS clinical trial.


We propose to accomplish this in a pilot study by

(1) Demonstrating the available features of the automated tool using an ongoing clinical trial, the NINDS funded POINT trial.

(2) Comparing the performance characteristics of the automated tool to a traditional patient recruitment method for screening and enrollment.


Our specific aims are to:

Specific Aim 1: To identify and document study subject characteristics that will be used in developing a screening criteria for the automated tool (Phase 1)

Specific Aim 2: To demonstrate the performance characteristics and comparative effectiveness of automated real-time screening tool using the ongoing  clinical trial in the emergency department at UCSF (Phase 2)

Hypothesis: Automated screening will be more sensitive, and less specific than the traditional method of using research assistants in identification of subjects.

Specific Aim 3: To demonstrate that the operation of real-time clinical research eligibility screening meets HIPAA privacy requirements and does not compromise PHI.

Hypothesis: The technologies and architecture that is employed in developing the Patient Locate service will be sufficient to ensure that HIPAA privacy requirements can be met.

Study Design: In the first three months of the study, we will study the baseline characteristics and presenting symptoms of the eligible study subjects as well as patients enrolled in POINT. We will use the information to develop screening criteria which will be tested in the second phase of the study. During the second phase  KDH system will be activated to identify study eligible patients and the effectiveness of the tool will be compared with the traditional method of recruitment.


Metrics: Sensitivity, specificity, positive and negative predictive value, and likelihood ratios will be calculated to determine the screening performance of the automated screening tool system for eligibility. The performance characteristics will be compared to the research assistant supported system currently in use at UCSF. 95% confidence intervals will also be calculated to assess the strength of the point estimates.

Anticipated result and impact on trial enrollment procedures:

Upon the culmination of this study, the results will help our research team and the CTSI better understand the relative merits of the automated real-time patient recruiting system.

Budget and Justification: Salary support for the investigators and a research assistant for a 12 month period ($60,000)

Collaborators: John Stein (Co-PI), Department of Emergency Medicine, Claude Hemphill, Department of Neurology and Dan Carnese, KDH systems


Commenting is closed.

Developing and testing mechanism-based translational hypotheses

Proposal Status: 

RationaleProblem: because of multiscale complexity, conceptual, mechanism-based, in vitro-to-in vivo mapping models are hard to falsify and can be flawed in ways that may not be obvious until challenged experimentally, which can be costly.  When the results of such experiments are equivocal or not supportive, the information needed to revise mechanistic hypotheses may be lacking.  Translation of in vitro phenomena to in vivo counterparts requires a mapping model.  Currently, mechanism-agnostic correlation models are common.  When translation is based on hypotheses about underlying mechanisms, the mapping model is almost always conceptual, often described in prose, supported by diagrams and, occasionally, mathematical models.  Solution: explicitly instantiate mechanistic mapping models in silico and explore their feasibility.  We envision concrete, computational, observable-in-action, experimentally challengeable mapping models that will evolve to become executable knowledge embodiments showing what does and does not translate under specific conditions.

The concept is illustrated in a recent paper (PMID: 20406856), “Tracing multiscale mechanisms of drug disposition in normal and diseased livers.”  We used, improved, and revalidated a multiscale in silico liver (ISL).  An ISL is an example of a new class of computational models.  We posited that changes in micromechanistic details from normal to diseased ISLs may have disease-causing, hepatic counterparts.  Together, the ISL and in silico methods represent an important step toward unraveling the complex influences of disease on drug disposition.  We demonstrated translating—morphing—a validated “normal” ISL into a “diseased” ISL.  Although ISLs are abstract software constructs, that transformation stands as a concrete, mechanistic hypothesis about what does and does not translate from one to the other.  The methods, which are new and novel, are designed to be extensible to whole organisms and, eventually, patients.  Being able to transform one validated ISL into another is important: it is evidence that the approach can be used to explore and challenge ideas about translation, making translational research more concrete. 

We envision “translational models” showing how, for example, in silico micromechanistic details are morphed between analogues of in vitro rat and human hepatocyte cultures, and in time between in vitro computational analogues and human analogues.  The morphing process will show what must be added and what is lost in translation.  A long-range goal for such morphings will be to provide an easily understood, mechanistic interpretation of how cause-effect relationships resulting from an experimental intervention in a wet-lab model are believed to manifest (or not) in a human analogue.  The expectation is that those relationships will have real world counterparts. 

Plan.  An essential precondition for achieving the above vision is to have two different, biologically related models (e.g., in vitro & in vivo) that have independently achieved validation targets.  We will focus on the above-cited ISLs and improved versions of in silico hepatocyte (ISH) cultures (PMID: 21768275): we will focus on translation of phenomena measured in hepatocyte cultures to corresponding, location dependent phenomena within hepatic lobules in rat and human livers.  We have designed the models so that hepatocytes can be exchanged: ISHs that have achieved validation targets under different culture conditions (ongoing during year one) can be plugged into an ISL (after its hepatocytes are removed).  The iterative refinement needed to reestablish whole-liver validation targets (including intralobular zonation) will provide a concrete theory of mechanistic attributes gained and lost in translation. 

Criteria and metrics for success.  1) Instantiation of quasi-autonomous ISH objects and documentation (a conference paper, e.g., the Winter Simulation Conference) that they can be transferred from one context (a simulated culture) to another (a simulated lobule) while retaining all the mechanistic features validated in vitro.  2) Produce a draft manuscript that demonstrates that an ISL with these new hepatocytes can also achieve whole liver phenomena, such as zonation of enzyme induction.  Produce a draft manuscript by year’s end for submission within the following four months. 

Approximate cost and brief justification.  Achieving 1 & 2 above will require several hundred cycles of iterative refinement (1 postdoc @ $48K working full time with Dr. Hunt) of in silico components (described in PMID: 20406856).  Simulation, publication, and meeting costs bring the total to $58K. 

Collaborators. Jackie Maher, UCSF Liver Center

Commenting is closed.

A Clinical Research Toolkit for Surgeons in Low Resource Environments

Proposal Status: 


Less than 8% of orthopaedic research originates in low and middle income countries (LMICs), despite the fact that 95% of deaths from road traffic accidents occur in these countries.  Global partners of the Institute for Global Orthopaedics and Traumatology (IGOT) have asked for assistance in building the capacity to perform clinical research.  This is important because:

  • Research fuels advocacy, drives policy decisions and guides the allocation of resources in medicine.
  • The orthopaedic surgeons who address the burden of musculoskeletal disease in LMICs struggle with a lack of research resources, literature irrelevant to their practice and professional isolation. 
  • Researchers in resource-poor settings are essential partners to UCSF's goal to 'promote health worldwide'. 

This project will address these issues on three fronts:

  • Design a digital toolkit of research resources leveraging existing resources such as CTSI’s online research tools, the Department of Orthopaedic Surgery’s Research Bootcamp, and EpiInfo 7.
  • Select a platform that will function using the most commonly available technological resources, and integrate mentoring and support between experts and learners.
  • Evaluate program effectiveness and sustainability based on partner feedback and marginal costs, respectively. This evaluation will help to guide content, platform and operational improvements, before the project is made widely available in other settings (other LMIC partners as well as resource-poor and isolated locations in the U.S.).

Our goal in creating this toolkit is to build the ability of trainees and surgeons anywhere to plan, implement and publish relevant research.  We are piloting this program in the most resource-constrained environments in order to allow future scaling of the toolkit in sites that have access to more resources.  Our long-term goal is to establish a generalizable suite of tools akin to the resources available for students through the Khan Academy or MIT OpenCourseWare.


IGOT has completed interviews that explore the barriers to research in LMICs, and has used the subsequent analysis to tailor content that addresses these barriers. IGOT has also completed research related to the optimal format for content delivery in LMICs.  These initial steps lay the foundation to start work immediately on content and platform development.


Project Plan

  1. Select a format for content delivery based on available technologies that provides access to the widest range of users.
  2. Prove content validity of the toolkit’s curriculum through consultation with expert clinical researchers in orthopaedic surgery and with academic orthopaedic surgeons in LMICs (modified Delphi analysis).
  3. Create simple web-based tools such as webcasts or podcasts for each of the topics, a research question formulation tool and templates for creating proposals and budgets that will live on the IGOT website (www.globalorthopaedics.org).
  4. Create a research proposal forum that allows posting, feedback and partnering on projects.
  5. Pilot the toolkit in Lahore, Pakistan and Kathmandu, Nepal.
  6. Iterate the program based on feedback from the charter sites for future program expansion.
  7. Determine the overall program cost and marginal site cost to determine the expected return-on-investment of the program in the future.

Success Metrics

  • Improvement of methodological quality of thesis proposals after program participation based on the Journal of Bone and Joint Surgery (American) levels of evidence (http://www.jbjs.org/public/instructionsauthors.aspx#LevelsEvidence) based on an analysis of current and 2013 resident thesis projects
  • Website Analytics
    • New and Repeat Page Views
    • Length of View
  • Use of Toolkit – mandatory at sites after first class with resident and faculty champion established at each site.
  • User Satisfaction – Participants average satisfaction 75% based on post-program survey
  • Research proposals entered into global orthopaedic trial registry by each pilot site
  • Secure one pilot site in the Bay Area for implementation in the second year of the program


Cost and Justification

Estimated cost $45,000 composed of labor to analyze data held at the Institute for Global Orthopaedics and Traumatology (20%) as well as content generation and web development for the toolkit (76%) and project management (4%).  One of this project’s strengths is that it leverages existing content and will utilize a cost-effective digital delivery method.  This will allow the program to become sustainable and have a lasting impact after the initial investment in the program.



Syed Mohammed Awais (Dean, King Edward Medical School and Mayo Hospital, Lahore, Pakistan), Ashok Banskota (Founder/Surgeon Rehabilitation Centre for Disabled Children, Kathmandu, Nepal), Amber Caldwell (Director of Development, IGOT, UCSF), John Collins (Educational Studies, University of British Columbia), Richard Coughlin (Founder/Director, IGOT, UCSF), Richard Gosselin (Co-Founder/Co-Director, IGOT, UCSF), Harry Jergesen (Co-Founder/Co-Director, IGOT, UCSF), Saam Morshed (Clinical Trialist/Orthopaedic Surgeon, UCSF), Theodore Miclau III (President Orthopaedic Research Society/Founder and Director Orthopaedic Trauma Institute), Aenor Sawyer (Paediatric Orthopaedic Surgeon), Daniel Sonshine (IGOT research Fellow), Paul Tannenbaum (Web Developer, IGOT, UCSF), Angelique Slade Shantz (Project Manager, Orthopaedic Trauma Institute, UCSF)

Commenting is closed.

Improving Capacity for Translational Research in Tuberculosis

Proposal Status: 

Rationale: The purpose of this application is to strengthen the tuberculosis (TB) translational research capacity at UCSF/SFGH by developing a BSL-3 laboratory in which work with human TB can be safely carried out in tissue culture and in small animal models.  Such work will enable us to extend observations that we have made in molecular epidemiological studies of TB in San Francisco, permit new lab-based investigation in the context of existing, funded clinical studies in San Francisco and abroad, and facilitate additional studies in animal models of infection. Having such a facility will enable us to examine immunological responses to as well as the pathogenicity and virulence of clinical strains of M. tuberculosis (M.tb) isolated from patients in San Francisco and in other areas across the US and globally, and to study the impact of co-infections with M.tb and other pathogens (e.g., HIV). We have a superb multidisciplinary group of investigators working in the US as well as in Kenya, Tanzania, Zimbabwe, Uganda, and Vietnam in studies of the transmission and pathogenesis of TB. In a number of these studies, observations have been made that suggest differences among strains and interactions between specific strains and hosts of specific race/ethnicity. Examination of these findings in lab-based studies and/or in an animal model will, if confirmed, enable back translation to human studies and approaches to vaccine and drug development. The availability of a new BSL-3 will facilitate the work of investigators working across many disciplines and enable questions to be addressed that can only be examined in animal models. Given the international scope of existing research activities, this effort will also mesh with efforts at UCSF and SFGH to enhance global health. In recent efforts to recruit an investigator focused on TB immunology, the major limiting factor has been the lack of BSL-3 space. Thus, having such a facility is a critical element in filling a critical deficiency in our TB research program.

Plan: Although a BSL-3 laboratory exists in Building 100 at SFGH, this laboratory is heavily utilized, inadequately designed, and not amenable to the maintenance of M. tb infected animals. Other alternatives have been carefully explored but deemed not feasible for reasons of experimental protocol, safety, and/or cost. We propose to upgrade an existing BSL-2 laboratory in Building 3, a seismically sound building, to BSL-3 status. Based on input from the construction firm that built the existing space, the total cost of the build-out of the BSL3 is estimated to be $1.2M. There is widespread enthusiasm and broad support to create such a facility, as indicated by commitments that total $950,000 from a consortium of funders including the Department of Medicine, the Medical Service at SFGH, the SFGH Dean's Office, and the Ireland Fund, but there remains a $250,000 deficit. We are asking for $100,000 to help leverage these commitments. Given our success in raising the needed funds, we are confident that the additional $150,000 will be secured, even if it means obtaining a loan that would be paid back by users over time.

Criteria and Metrics for Success: The single metric will be the hiring of one independent TB immunology investigator by 2013. The Division of Experimental Medicine will commit the resources for at least one start-up package to hire faculty members focused on the immunology of human TB. Each package would include at least $1M in start-up funds and the provision of BSL1 and BSL2 space ensuring that, if the BSL-3 is built, the criterion of success will be met.

Approximate Cost and Justification: We are requesting $100,000, an amount that will be combined with additional resources that have already been committed (see above). These aggregated funds will be used to purchase or construct: 1) animal holding space with self-contained cage ventilated racks for mice or guinea pigs; 2) several biosafety cabinets for the safe handling of M.tb in tissue culture; 3) autoclave alcove to house the autoclave and the CO2 gas manifold; 4) clean vestibule (entrance and exit); 5) dirty vestibule (entrance to both of the laboratories and the animal holding room); and 6) ultralow freezer for storage of bacterial stocks and infected tissues. The space will have the mechanical system required for a completely independent ventilation system.

Faculty who would use this facility: Hopewell, Havlir, Kato-Maeda, Catamanchi, Davis, Metcalfe, Nahid, Everett, Cox, McCune, Nixon

Commenting is closed.

“Expedited” Expedited CHR submission and approval for Chart Review Research (Category 5)

Proposal Status: 

Title: “Expedited” Expedited CHR submission and approval for Chart Review Research (Category 5)


Rationale: Clinical researchers often perform retrospective, chart-review studies as a relatively inexpensive and quick way of determining which clinical questions are worth pursuing before engaging in more expensive, time-consuming prospective studies.


Chart-review studies also play a critical role in developing and generating new scientific hypotheses, and their role in the hierarchy of research methodologies is indispensible.  For junior researchers, who often do not have much in the way of funding or protected time to do research, chart-review studies provide an essential way to get early experience doing research. 


Chart review studies qualify for expedited CHR review under federal regulations, 45CFR46.110, Category 5.  Currently, however, the time and effort required to go through the process of expedited approval is substantial and serves as a deterrent to performing this type of research at UCSF.  The current UCSF CHR form for an expedited chart review (Category 5) study is 20 pages long and empirically cumbersome to fill out.  An estimated 80% of the forms have to be returned to the researcher by the CHR for revision, and usually there are multiple iterations between the researcher and the CHR to correct the form before approval is given.  This back-and-forth is time-consuming and frustrating for both researchers and CHR staff, and slows the pace of research at UCSF.  While the CHR makes every effort to perform these reviews in an expedited fashion, the median time-to-approval for (all expedited categories) is 32 days, which is significant for a researcher who may have only a month or two protected to perform research. 



We propose to simplify and truly streamline the process for obtaining “expedited” CHR approval at UCSF for research projects that involve no-subject contact and are confined strictly to chart review (Currently under Category 5 for expedited CHR review).


It is noteworthy that in some jurisdictions, such as the United Kingdom, non-subject contact chart review to conduct an audit to reflect on one’s own practice is encouraged by the physicians licensing authority as an adjunct to continuing practice rights. Reflection on practice is an important part of continuing practice improvement. What is proposed here is, therefore, completely consistent with comparable demands around such activities in other places.




In a direct collaborative effort between UCSF clinical researchers from various specialties and the UCSF Human Research Protection Program staff, we plan to develop a highly streamlined online application form for applying for CHR approval for Category 5 chart review studies. With this unique collaboration, this project is “shovel-ready.”


The questions on the form will be clearly written and focus-group tested to ensure they are easily understood even by novice researchers.  This is to ensure that the form can be completed quickly, optimally in less than fifteen minutes, and accurately so that iterations wherein the CHR has to return the proposal to the researcher for corrections are minimized.  The streamlined form will also be easier for the CHR to review, which should allow for a truly expedited review process and approval.  Internally, the CHR plans to have these forms handled by a consistent small group of analysts so that they can build familiarly with the forms, trouble-shoot efficiently, and keep approval times down. The form will also have clear and simple screening questions to ensure that such proposals truly do fall under the Category 5 designation.


 This proposal will satisfy the Federal Common Rule that requires the conduct of human research receive IRB approval prior to the initiation of the research, as well as the HIPAA requirement that a privacy board, in this case the CHR, reviews the study proposal prior to using Protected Health Information for research.


As part of this project we will develop a new reports within iMedRis that can provide the average and median number of iterations (submission rounds) required for approved research, with filters for application type, submission type, type of research, type of funding, time period, investigator, IRB panel, and HRPP analyst.  We will also enhance other reports of time-to-approval, and add a measurement of the time it takes investigators to prepare a CHR submission.  With these reports we will be able to compare data from current Expedited Category 5 approvals, to data from the new form we generate, and measure improvements in several ways.  Note that these reports will be permanent and can be used to provide UCSF better data on the IRB submission process for all research, including clinical trials.



Criteria and metrics for success:

Our proposal will have succeeded if at the end of the one-year implementation period we have:


1. Developed a concise online form that has been focus-group tested on clinical researchers and approved for use by the UCSF CHR for the purpose stated above.


2. Completing the concise form takes no more than fifteen minutes (on average), even for a novice, junior researcher (e.g. resident or fellow) in our focus-group testing.


3. There is a ≥50% reduction in number of iterations required to get CHR approval for these studies compared to current baseline for Category 5 expedited review studies (baseline iteration data to be generated by new reports within iMedRis). This would also have the indirect benefit of freeing up CHR staff time to focus on other categories of applications, hopefully improving approval times overall.


4. There is a ≥50% reduction in time to approval (measured in days) compared to current baseline for Category 5 expedited review studies (baseline iteration data to be generated by new reports within iMedRis). 


5. We have generated a report system that can be used by the UCSF CHR to provide better tracking data on the IRB submission process for all research done at UCSF, including clinical trials. 


Total Budget: $16,574

Salary support for project leader and research coordinator; two stipends for clinical research collaborators ; printing costs and supplies; focus-group participant compensation.




Amy Gelfand, MD (PI) : Dr. Gelfand is a child neurologist and a clinical researcher in pediatric headache. She will serve to oversee the project, including coordinating with the HRPP staff and clinical researcher collaborators, running the monthly research team meetings, and submitting study progress reports to CTSI.


John Heldens, HRPP Collaborator: As the director of the Human Resources Protection Program at UCSF, Mr. Heldens will oversee the iMedris and HRPP staff and supervise the form changes.  He will vet the new mechanism of CHR documention with Privacy, Legal, HIMS, and IT security.


Vanessa Jacoby, MD: Dr. Jacoby is a clinical researcher in OB/GYN at UCSF. She will attend monthly team meetings and give feedback on the form questions as they are being written and implemented.  She is familiar with the needs of clinical researchers who work with vulnerable populations (i.e. pregnant women), and who perform surgical procedures as well as outpatient and inpatient clinical care.


Vanja Douglas, MD: Dr. Douglas is an adult neurologist whose clinical research focuses on inpatient neurology.  He will attend monthly team meetings and give feedback on the form questions as they are being written and implemented. He is also a Journal Editor so will ensure that the needs of journal editors to be assured that research studies they are publishing received appropriate CHR approval are being met by the new submission and approval process.  

Commenting is closed.

Evidence-based Inputs for Sample Size Calculations: A Web-based Application

Proposal Status: 

Rationale:  Inaccurate sample size estimation leads to research studies that enroll too few or too many study participants. The former can result in failure to demonstrate anticipated effects and the latter to excessive costs, due to overuse of research participants and personnel time. While there are several important components of a good sample size calculation – including a compelling research question, an appropriate outcome variable, and an efficient study design – here we focus on improving the accuracy of the quantitative inputs. Examples of such parameters include:  

  • the variability of responses within and between eligible participants (accounting for correlations among replicate measurements at a given time and/or at different times),  
  • the mean response under standard-of-care conditions, and
  • the prevalence of the disease under study.

At present, the primary sources of parameter values are pilot studies (often too small to provide reliable estimates) and published studies (which often lack the needed values). Estimates of parameter values that are not evidence-based can introduce a large amount of error into the sample-size calculation, making it precise but inaccurate. The proposed web-based application would allow a clinician and biostatistician to identify required values in real time during a consulting visit, revising the query as needed to ensure a viable and cost-efficient study.  Given the enormous number of medical studies launched every year, access to accurate inputs to sample size calculations could vastly reduce waste of valuable resources.


Plan: The two key ingredients to obtaining a wide range of evidence-based inputs for sample size calculations are the availability of electronic sources of current health information and a convenient means of retrieving relevant information from the databases. During pilot funding, we will demonstrate feasibility of (1) identifying relevant existing databases; (2) quantifying improved accuracy of sample-size calculations based on of evidence-based parameters (as defined here) relative to those based on other sources of inputs; and (3) producing version 1 of a user-friendly web-based interface to access, summarize, and output evidence-based parameters in useful formats. Beyond pilot funding, additional databases could be tapped, and the breadth of access, summarization, and output could be expanded. 

Aim 1:  Identify Databases:

  • Ideal databases should provide longitudinally tracked individual-level health outcomes related to a wide range of conditions. Two excellent examples appear to be (1) Databases included in the UCSF CTSI Large Dataset Inventory, accessible at no cost through http://accelerate.ucsf.edu/research/celdac.  (Example: National Health Interview Survey) (2) The Kaiser healthcare database. [Must: Identify key personnel who could provide access, engage their interest, and establish an agreement to collaborate.]
  • With clinical partners: Establish a set of commonly expected requests that could be used to evaluate candidate databases on quality and availability of desired data.  
  • With database partners and computer experts: Optimize access to and manual retrieval of information.

Aim 2:  Proof of Concept  

  • Identify commonly used outcome variables and alternative choices through review of the published literature and discussion with clinical colleagues.
  • Identify a selection of recently published high-profile studies that reported the values of key study design parameters. For each: (1)  Document the eligibility criteria and parameter values that were used in the study design. (2) Document corresponding values drawn from the selected databases. (3) Examine the effect on the sample size of differences between the two sets of parameter values.

Aim 3: Create a web-based user interface, a manual of procedures with useful examples, and useful export files.

  • User experience:

          o   Make retrieval fully dynamic: any outcome stored in the database; retrieval tailored to major eligibility criteria (e.g., age and diagnosis) and design criteria (e.g., frequency of assessment per patient).

          o   Use drop-down menus, populated by database-specific data dictionaries, to ensure accurate spelling.

          o   Produce results that are easy for the investigator or biostatistician to manipulate. The software will process all (or a random sample of) eligible values to generate rates (see example appended), means, variances, and correlations, as needed. 

          o   Generate downloadable documentation of queries for user’s later access.

  • Developer experience:

         o   As queries of a database are made, record queries (including search criteria) and results.

         o   Identify unavailable measures; examine reasons. Automate or prompt search for an alternative database and/or measure.


Criteria and metrics for success:

Aim 1:  Compare the proposed database resources in terms of features, data quality, and costs: 

  • Are Common Data Elements used?
  • Is a data dictionary available for sorting and browsing to find measures available?
  • Does resource have the requested measures?
  • How current are the measures?

Aim 2:  For a range of recently published studies that reported the values of key study design parameters, evaluate the effect on the sample-size calculation of differences between reported parameter values and values retrieved from our proposed database resource(s).  Hypothesis:  Evidence-based values will modify the sample size calculation by at least 10%.   

Aim 3:  Compare the proposed database resource(s) in terms of ease of access and value of information gained: 

  • Poll users to obtain feedback on ease of use and value of information retrieved, by database.  
  • Summarize measures queried by frequency. 
  • Characterize variation among databases with respect to comprehensiveness and ease of use.
  • Estimate personnel costs associated with building database access.


Cost:  We seek funding to access at least two large free databases by leveraging the CTSI Large Database Inventory [Aim 1], to quantify the benefit of evidence-based parameter values on sample-size calculations [Aim 2], and to plan the computational work in fine detail [Aim 3].  Salary support $100,000 (12 months) for principal faculty and staff.


Collaborators: Joan Hilton (Epidemiology & Biostatistics) will lead the biostatistical aspects of the “App” development.  Tracy van Nunnery (Medicine) will lead a team of computer experts who will create the database interfaces. Kirsten Bibbins-Domingo (Medicine) will serve as lead clinical collaborator.


Example interface and output:  Dr Hilton and Mr Nunnery have on-going research collaborations that began in 2007. Mr. Nunnery and his team created HERO, the electronic medical record system used at Ward 86 of SFGH, and thus are well acquainted with HIPAA requirements. As an example of their work, users (clinicians) can query HERO to obtain the distribution of any patient characteristic captured by clinicians, limited to user-specified search criteria. The web-based interface for retrieving demographic data is shown below, with the date fields displayed (upper image).  The distributions of demographic characteristics were exported to an Excel spreadsheet (lower image).

Commenting is closed.

Translating an Effective Systems-Based Chlamydia Screening Intervention For Australian General Practitioners in New South Wales

Proposal Status: 

Rationale Chlamydia trachomatis remains the most commonly reported bacterial sexually transmitted infection among U.S. females between the ages of 15 and 24 years.1 Most infections are asymptomatic and if untreated can cause major reproductive morbidity.2 Screening for chlamydia has been shown to be cost-effective3 and is recommended for all sexually active female patients 24 years or younger.4 Yet, improvements in screening rates have been small.5 We developed a systems-based intervention to identify and screen at-risk sexually active adolescents which, in a randomized control trial, resulted in dramatic increases in screening rates in a large Northern California Health Maintenance Organization (HMO).6-8

The Chlamydia infection rate in Australia has tripled over the past 10 years, with New South Wales having the second highest rate of infection in Australia.9 As a result, an international systematic literature review was conducted to examine chlamydia prevention programs that have published sustainable and significant increases in routine screening within the primary care setting. The review identified 23 full text articles that met the inclusion criteria, 4 review articles were excluded and the remaining 19 were analysed based on their level of impact and then later based on their relevance within an Australian context. This analysis identified articles by Shafer and Tebb 6-8 as having the potential to be applied in the Hunter New England Local Health District of New South Wales (HNELHD).10 Efforts to translate this intervention into primary care general practices (GP) took place between March 2012- Dec 2012 with Dr. Tebb consulting on the translation methods and materials. Implementation efforts are scheduled to begin June 2012.

The purpose of this proposal is to support this collaborative international partnership to translate, implement and evaluate our chlamydia screening intervention in the HNELHD setting in order to address this major public health epidemic. General practice is considered an ideal setting for population based chlamydia prevention initiatives given its reach to the youth population; with 80-85% of young women, and around 65% of young men visiting a GP annually.11,12 GP is also considered an acceptable and feasible setting in which to provide routine and sustainable chlamydia care to young people at the population level.13

Plan: to tanslate and evaluate our successful Chlamydia screening intervention into 17 GPs in HNELD region. The aims of the practice-based phase are to develop policies, systems and processes to support routine chlamydia screening for all sexually active 15-24 year old patients, and to establish a quality improvement cycle to continuously improve the proportion of at-risk females 15-14 years of age who are screened for chlamydia. Selection criteria for the 17 GP sites were: one major urban area from each of the three clusters that has the highest youth population (15-24 years); 50% of the GP practices in each of the three urban areas with the highest number of active young patients; capacity, and willingness to take part in the project. The practice sites are as follows: 9 from Greater Taree, 7 from Cessnock and 1 from Muswellbrook. The approach will modify the tool kit and strategy used in the original HMO intervention so it is applicable to this new setting. It will also develop step by step information to support project translation and replication efforts. We will evaluate pre-post differences in the proportion screened adjusting for repeated measures and GP region.

Criteria and Metrics For Success A pre-post-test clinical audit intervention conducted with general practices(GP) across three primary care divisions within the HNELHD in 2008. Suggested that providing chlamydia care to over 70% of young people who frequent the GP setting is achievable, as measured by GP self-report, however the follow-up needs assessment found that less than half of the GPs surveyed continued to routinely offer chlamydia screening to their 15-25 year old sexually active patients.14 It has been shown that 50-70% of young people aged 15-24 years need to be tested and treated for chlamydia to see reductions in the incidence at the population level.15 We will use this criteria as the primary metric of success. Statistical analyses will compare pre-post changes in the proportion of adolescents screened for CT across each of the GP practices that implement the intervention. A process evaluation will be conducted to evaluate barriers and facilitators to identifying and screening asymptomatic, sexually active adolescents and young adults for chlamydia.

Cost and Budget Justification: The estimated cost for this proposal is $97,800 to support PI (Dr. Tebb) at 30% effort, Co-Investigator (Dr. Shafer) at 10% effort; Statistician (Dr. Nehaus) at 5%; 2 part-time local data collectors $30K and 1 round trip travel for PI at $3,000 and minimal supplies at $1,000.

Collaborators: Hunter New England Health (HNEH) provides care for approximately 840,000 people and covers a geographical area of over 130,000 square kilometres (including Hunter Region, the New England Region and the Lower Mid North Coast local government areas of Gloucester, Greater Taree City and Great Lakes). The Chlamydia Prevention Quality Improvement project is a collaborative project with the Hunter Rural Division of General Practice



  1. Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance, 2009. Atlanta, GA: Centers for Disease Control and Prevention. Division of STD Prevention National Center for HIV, STD and TB Prevention; 2010.
  2. Chesson HW, Pinkerton SD. Sexually transmitted diseases and the increased risk for HIV transmission: implications for cost-effectiveness analyses of sexually transmitted disease prevention interventions. J Acquir Immune Defic Syndr. 2000;24(1):48-56.
  3. Hu D, Hook EW III, Goldie SJ. Screening for Chlamydia trachomatis in women 15 to 29 years of age: a cost-effectiveness analysis. Ann Intern Med. 2004;141(7):501-513.
  4. US Preventive Services Task Force. Screening for chlamydial infection: US Preventive Services Task Force recommendation statement. Ann Intern Med. 2007;147(2):128-134.
  5. National Committee for Quality Assurance. The State of Health Care Quality: 2010. Washington, DC: National Committee for Quality Assurance; 2010.
  6. Shafer MA, Tebb KP, Pantell RH; et al. Effect of a clinical practice improvement intervention on chlamydial screening among adolescent girls. JAMA. 2002;288(22):2846-2852.
  7. Tebb K. P., Pantell R. H., Wibbelsman C. J., Neuhaus J. M., Tipton A. C., Pecson S. C., Pai-Dhungat M., Ko T. H. & Shafer A. B. (2005) Screening sexually active adolescents for chlamydia trachomatis: What about the boys?, American Journal of Public Health, 95 (10): 1806-10.
  8. Tebb K, Wibblesman C, Ko T, Neuhaus J, Shafer MA (2011) Translating and Sustaining a Chlamydial Screening Intervention 4 Years Later. Arch Intern Med, 171(19):1767-1768.
  9. Centre for Epidemiology and Research. 2009 Report on Adult Health from the New South Wales Population Health Survey. Sydney: NSW Department of Health, 2010.
  10. Guy R.J., Ali H., Liu B., Poznanski S., Ward J., Donovan B., Kaldor J. & Hocking J. (2011) Efficacy of interventions to increase the uptake of chlamydia testing in primary care: a systematic review, BMC Infectious Diseases, 11.
  11. Centre for Epidemiology and Research. 2009 Report on Adult Health from the New South Wales Population Health Survey. Sydney: NSW Department of Health, 2010.
  12. Kong, F. Y. S., Guy, R. J., Hocking, J. S., Merritt, T., Pirotta, M. Heal, C., Bergeri, I., Donovan, B. and Hellard, M. E. (2011) Medical Journal of Australia; 194(5): 249–252
  13. Donovan, B., Bodsworth, N. J., Rohrsheim, R., McNulty, A., and Tapsall, J. W. (2001) Characteristics of homosexually-active men with gonorrhoea during an epidemic in Sydney, Australia. International Journal of STD and AIDS, 12:437-443
  14. Chlamydia care in general practice.  Draft report. Hunter New England Population Health. 2010
  15. Frileux, S., Sastre, M.T.M, Mullet, E. & Sorum, P.C. (2004) The impact of the preventive medical message on intention to change behaviour, Patient Education & Counselling, 52:79-88

Commenting is closed.

Video Series to Support Translational Research and Development

Proposal Status: 

The Challenging Path from Bench to Bedside
Although basic and clinical scientists have long collaborated, translational research challenges investigators to move beyond the traditional training of both laboratory scientists and clinicians. The delivery of effective clinical solutions involve the integration of science, technology, intellectual property, market analysis, product development, clinical, regulatory and reimbursement strategy, and marketing. These are clearly very different disciplines and functions, practiced by professionals with very different backgrounds and experiences. Nevertheless, early investigators benefit tremendously from an appreciation for how these various factors affect the likelihood that an innovation will successfully lead to clinical implementation. In the T1 Catalyst Program at UCSF CTSI, we work closely with investigators to identify and support key innovations that are likely candidates for translation. Common concerns and questions about the many challenges in translating basic research toward clinical practice are routinely discussed.

A Video-Based Initiative to Trigger Early Engagement and Collaboration
We propose the production and targeted distribution of a series of brief (3-5 minutes) professional videos to broaden the dissemination of this information, and highlight UCSF and external resources available to support investigators tackle these challenges. The videos will illustrate a number of case studies through engaging narratives of the experiences and challenges faced by investigators, administrators, and business professionals at UCSF and private organizations. The impact of each case study will be further bolstered by highlighting the stories of the ultimate beneficiaries of successful translational research - patients.

This pilot project will focus on five key topics: needs assessment, intellectual property, strategic partnerships, getting to first-in-human clinical trials, and regulatory strategy. These videos will not provide in-depth analyses of each subject, but be a catalyst for viewers to assess their own needs, discover available resources, seek further information or assistance, and share their thoughts and ideas. Within UCSF, we will also highlight the expertise at the Office of Technology Management (OTM), the Office of Innovation, Technology and Alliances (ITA), the Institute of Quantitative Biosciences (QB3), and others to provide a more complete view of the resources available to investigators. Our objectives are: (i) to inform interested UCSF investigators of the key challenges to translational research, (ii) to persuade them that UCSF (and its partners) can support them to be successful; and (iii) to inform external organizations that UCSF is a valuable partner for translational research and development.

Leveraging Storytelling, Consumer-Generated Content and Social Networking
To maximize reach and impact, the videos will tell a number of stories, that weave together the many facets of translational research. These will not be instructional videos. They may include dramatized re-enactments, and character development that convey the many, often opposing, objectives of stakeholders. The videos will be hosted and promoted through traditional and non-traditional distribution channels that not only target public and private investigators, but their research assistants, and supporting administrators. This wider audience will be encouraged to participate in the narrative by providing feedback or sharing videos of their own experiences and concerns. These discussions will be further promoted to increase awareness and a sense of community and shared interest.

We will also coordinate promotion with other UCSF and UC communication channels (i.e. UCTV, etc.), as well as several external business and R&D groups. Distribution efforts may also include targeted email marketing, other CTSA network communication channels, outreach to relevant bloggers, etc. The outreach will be accompanied by viewer analytics to improve and customize future projects and campaigns.

Assessing Awareness and Long-Term Engagement
In the short term, we will measure the success of our project through viewer surveys. These surveys will be carefully designed to elicit information about the viewer's understanding of why and how translational research occurs, their interest in learning more, and ongoing concerns. In the long term, we will use the results from our outreach-based analytics, and measures of increased interest from UCSF and non-UCSF investigators and business professionals, to assess the impact of this project (e.g. measured through the number and quality of applications to the T1 Catalyst Award Program).

An Experienced and Multi-Disciplinary Team
The project will be a collaborative effort between CTSI's Communications team and Early Translational Research (ETR) program. John Daigre and Katja Reuter (CTSI Communications) are experienced multimedia and social media professionals who will serve as advisors throughout the planning, production, and editing process, and take a leading role in the promotion phase. ITA, OTM, QB3 and other key UCSF-based institutions will also be major contributors to the project. An external video production company will be hired to help develop story lines, and produce and edit the videos. Ruben Rathnasingham (ETR), who has helped develop a number of university-based innovations into clinical products, will manage the project.

Total Budget: $40,000 

This pilot project will take 6 months to complete with a budget of $40,000 for planning, production, editing, and promotion. 

Commenting is closed.

Translating Research into Law and Policy

Proposal Status: 

Rationale: Currently, there is no direct pathway for health sciences research to move from scholarly publications into policy and law. Although some evidence is cherry-picked by advocates and policymakers, legislation often reflects rhetoric rather than evidence. While some translational researchers study the effects of laws or write white papers summarizing the state of the evidence, we know of none who take the approach of working with investigators to leverage their research and write model legislation. Here we propose the development of a replicable process that will translate research directly into evidence-based model policies, regulations, and laws that improve health and/or health outcomes. Model policies, regulations, and legislation are proposed pieces of law drafted by researchers working with legal scholars to incorporate the latest scientific evidence with the goal of improving health and/or health outcomes. The drafted language would then be made freely and widely available to legislators, advocates, and others involved in the enactment of law, regulations, and policy.  


1. Kick-off Meeting: March 30, 2012 to introduce the project and workshop additional ideas for a pilot project.

2. Pilot projects: This grant will fund one-two demonstration/pilot projects that bring together UC Hastings faculty, UCSF researchers, and students from both institutions to write evidence-based model legislation, regulations, and/or policies. This group will analyze both the current scientific evidence and the legal frameworks related to a health issue being investigated by a UCSF researcher; the group will then write model legislation that revises or changes current laws or that proposes new laws in order to improve health and health outcomes. One pilot project we are pursuing is on the toxic effects of sugar on health based upon Dr. Lustig's research (PDF attached). We are considering  a second pilot project. Current ideas include mandatory reporting laws in the emergency medicine setting, the effects of hospital and ED closure, the efficacy of orthopedic procedures, restrictions on activities of individuals with epilepsy, and implementation issues realted to the Affordable Care Act.


Criteria and Metrics for Success: The broad goal of this demonstration project is a proof of concept that then allows for replication and dissemination of this new approach for translating research directly into legislation:


1. Creation of model legislation and/or regulations resulting from biweekly meetings of the UCSF investigators, UC Hastings faculty, and students from both institutions and the dissemination of the work-product . Timeline: Spring 2012-spring 2013.

Documentation & Dissemination:

2. Document year-long process via a detailed white paper. 

3. Host 4 calls/virtual meetings to discuss and publicize model to organizations and institutions that would replicate this model.  This would occur via the CTSA Health Policy network. Timeline: Winter 2012-summer 2013.


4. Create a student group focused on the legislative process and the translation of research into the policy, regulatory, and legal realm.  Recruit 15-25 interested students to participate. Timeline: To start in spring 2012.

5. Identify internal and external funding options to sustain and expand the project. Apply for at least 2 grants during the pilot period. before grant period is up.  

Total Budget: $38,506

Salary support for UCSF faculty, Co-PIs and research assistants involved in developing the pilot projects, the Program Analyst to coordinate activities of this project, consultants, project supplies and communication.


1. UC Hastings: Jamie King, Jennifer Dunn, David Faigman, Sarah Hooper

2. UCSF: Dan Dohan (co-PI), Rob Lustig, Dennis Hsieh (co-PI), Richard Barnes, Jessaca Machado

Commenting is closed.

Data Management for Research Community

Proposal Status: 


CTSI’s Consultation Services Data Management Unit (DMU) is just one of the successful research resources available on campus to help UCSF faculty and staff with his/her research.  Along with many other data management services, the DMU also provides consultation in data processing to help transform research data into a statistically analyzable format.  In our efforts to provide consultation to the UCSF research community, we have realized that some trainees and faculty do not have the programming skills or resources to perform data processing tasks that are necessary to keep their research moving forward.  Complicated data merges and transformations require specific programming expertise to ensure that it is performed correctly.  Data management programmers, who can devote more time and effort to small projects, are needed.  The DMU’s ability to provide these services is very limited.  As a result, we have identified a gap in services that the Data Management Unit is currently able to provide.   

All research requires some level of data management programming.  This expertise exists far and wide across campus. Regrettably, there is not an easy way to identify these experts.  Our goal is to form a community of data managers on campus.  The purpose of this community would be to 1.) identify specific data management programming expertise across campus, 2.) pool resources by sharing job descriptions, computer programs, workflow processes and standard operating procedures, and 3.) identify data managers who are able to provide services on a short-term, variable-effort basis.     

Data management programming is an integral step in preparing research results. Expanding access to data management services that include programming will greatly impact the efficiency, accuracy, and productivity of research at UCSF.  By leaving complicated programming tasks to the experts, researchers will be able to spend more time writing grants and developing manuscripts.


Most data managers on campus are in the Analyst, Programmer Analyst or Biostatistician job title category.   With the help of UCSF’s Operational Excellence Human Resources group we would first survey all UCSF staff within these job classifications to find data manager and biostatistical programmers who would fit well into our Data Management for Research Community.   The two main inclusion criteria would include those with 1) data management/programming expertise and 2) who work in a research environment.  Those who fit the criteria will be invited to join the Data Management for Research Community.  Membership would provide access to data management resources and a subscription to a quarterly Data Management for Research Community newsletter.  In return, we would require that each person fill out a brief Data Management questionnaire to help identify his/her data management expertise as well as a follow-up questionnaire to assess satisfaction with becoming a member.  Specifically, the Data Management questionnaire would ask questions regarding the programmers area of research and UCSF department, level of experience in working with large national databases, clinical trials, observational studies, cross-sectional studies, etc., and level of expertise in various data management and statistical programs, including SQL, VisualBasic, FoxPro, MSAccess, SAS, Stata, SPSS, excel, etc.  We would also ask questions regarding his/her preference for different levels of engagement, such as, email, conference call and/or in person meetings.  Through this process we hope to create a network of managers/programmers who are able to work with the DMU, an inventory of data management resources, and opportunities for providing data management services on a short-term, variable-effort basis to those who need it.    

Total Budget: $25,343  

A 20% Analyst I for 12 months will be needed to survey staff, set up the questionnaire in RedCap and compile/store inventory of resources.  A 5% Programmer Analyst for 12 months will provide content to the newsletter and design the questionnaires. 

Criteria and Metrics of Success:  Number of data management programmers identified, overall response rate, rate of membership enrollment, inventory of data management resources, number of data managers who are able to provide services and satisfaction with membership.


Janet Coffman, MA, MPP, PhD and CELDAC,
Laura Bettencourt and the San Francisco Coordinating Center

Joe Hesse, Department of Neurology


Commenting is closed.

Improving CRS performance through application of Lean/6 sigma

Proposal Status: 

1.     Rationale – the science of operations.  

The “clinical research enterprise” faces 2 simultaneous and daunting challenges. It has to both contribute to filling the innovation gap in healthcare while at the same re-engineer itself to become more efficient & integrated across all scientific and social disciplines involved along the translation continuum. It is very much like trying to modify an aircraft while flying in it. Lean/6 sigma is one methodology among many others that can help deliver on this dual challenge. Indeed, this “science of operations” is grounded in robust data analysis to relentlessly reduce waste and variability. It also relies heavily on team-work and open lines of communication between functions, which is a conditioning factor for innovation. Since 2000 it has been increasingly used in hospital settings, with sometimes spectacular results on cost and quality of care delivered (see1 for references on improvement on mortality rates and waiting times).  It is now being tested in a translational setting2.  Liu (2006) describes an application of Six Sigma methods to achieve a reduction of 70% in cycle time for entry of case record forms in a phase III clinical trial, while maintaining a statistically acceptable error rate requirement3. Lean techniques have also been applied to streamline the drug discovery process in the preclinical phase of research.

The goal of this project is to demonstrate the potential of lean/6 sigma to a wide UCSF audience by applying it to the Clinical Research Services (CRS) program to effectively manage its overall performance, and improve Quality and Costs in areas where it is needed. CRS is indeed ideally located at the intersection of clinical and research care. It therefore provides an ideal laboratory to investigate how lean/6 sigma can help the clinical research enterprise transform from an “End-to-End” perspective.

2.     Plan & Scope.

The project will encompass the overall CRS program and will be executed by following a typical lean/6 sigma structure or DMAIC (Define, Measure, Analyze, Improve, Control) over a 12-month period.  The project scope includes an initial End-to-End process map and gap analysis of all services provided by CRS to further highlight priority areas based on feasibility and ROI. The End-to-End process map will start with the initial PI request for CRS services and will end with their successful delivery.  From the initial assessment, detailed data collection plans, analysis, and solution proposals will be drafted and presented to the appropriate stakeholders to obtain endorsement for the chosen solutions.  Below are the strategies and expected deliverables per DMAIC phase that will be followed to conduct the initial and final assessments across CRS:

  • Define Phase (2 Months):
    • Intent: Define the problem statement and associated quantitative success criteria (i.e. Cost, Time, Speed) within the defined scope via an End-to-End process map.
    • Deliverables:  Project Charter, Voice of the Customer (VOC), High-level Process Maps (i.e. SIPOC), Communication Plan, and Project Plan.
  • Measure Phase (2 Months):
    • Intent:  Measure current performance on the previously determined success criteria across CRS.
    • Deliverables:  Data Collection Plan, Measurement System Analysis (MSA) – As needed
  • Analyze Phase (2 Months):
    • Intent: Identify potential root causes by conducting correlation and root cause analyses.
    • Deliverables:  Stratification, Ishikawa Diagrams (As Needed), Correlation Analysis (As Needed)
  • Improve Phase (4 Months):
    • Intent:  Present proposed solutions for identified gaps to the appropriate stakeholders.  Based on the endorsed options and available resources, implement chosen solutions. 
    • Deliverables:  Gap Analysis, Proposed solutions and prioritization criteria (i.e. Time, Resources)
  • Control Phase (2 Months):
    • Intent:  Ensure the sustainment and effectiveness of the solutions implemented
    • Deliverables: Control Plan, Service Level Agreements (SLA), Training (as needed), Change in Policies/Operation Procedures (as needed). 

3.     Criteria and metrics for success

Anticipated success for this project is to generate improvements that allow CRS to decrease its total program costs by 5% (~ $750k). The rationale for this goal is to at least offset the 5% budget cut from the 2012 budget. Another success goal could be to align the improvement efforts with the long-term strategy of CRS, which is to increase its revenues. No target can be reasonably set on revenues at this moment but could by the end of the Measure phase.

4.    Total Budget: $73,980

The anticipated cost of this project is $73,980 to support a Project Lead at ~ 58% of her/his effort 

5.     Collaborators

From PET: Adel Elsayed, and from CRS: Eunice Stephens (ops manager), Wendy Staub (sample processing lab manager), Cewin Chao (Bionutrition Director), Kathy Mulligan (Metabolics director), Danusia Filipowski (Clinical Coordinator Core Dir), Nariman Nasser (Participant Recruitment Core Dir), Deanna Sheeley (Research Nursing Core Dir).



1.     Example of lean/6 sigma results in hospital settings:

  • St. Joseph’s Hospital changed the ER patient flow, allowing the hospital to treat at least 10,000 more patients annually. – Tampa Bay Business Journal 
  • The Pittsburgh Regional Healthcare Initiative cut the amount of reported central line-associated bloodstream infections by more than 50%. The rate per 1,000 line days (the measure hospitals use) plummeted from 4.2 to 1.9. – ASQ.org (American Society for Quality) 
  • H. Lee Moffitt Cancer Center and Research Institute is expected to increase procedural volume by 12%, which will add nearly $8 million annually in incremental margin. – Tampa Bay Business Journal 
  • A large metropolitan hospital system reduced inpatient transfers by 75% and has $2 million annual cost savings. – iSixSigma.com 
  • A top-five hospital system used Lean Six Sigma to redesign its transplant unit and as a result improved patient satisfaction by 50% within three months; the cost of care was reduced by 15%. – Quality Digest
  • St. Vincent Indianapolis Hospital made a 78% cut in the number of steps emergency department nurses take to get supplies. – USA Today
  • A major hospital in the United States was able to reduce inpatient mortality rates by 47.8%. – iSixSigma.com
  • North Mississippi Medical Center reduced the number of prescription errors in discharge documents by 50%. – ASQ.org(American Society for Quality)
  • The Mayo Clinic’s Rochester Transplant Center reduced the cycle time from when a new patient made initial contact to setting up an appointment from 45 days to 3 days. – iSixSigma.com

2.     The Applicability of Lean and Six Sigma Techniques to Clinical and Translational Research, Sharon A. Schweikhart, Ph.D. and Allard E Dembe, Sc.D.The Ohio State University, College of Public Health, Center for Clinical and Translational Science, Center for Health Outcomes, Policy, and Evaluation Studies
3.     Lui EW. Clinical research: the Six Sigma way. J Assn Lab Automat. 2006;11(1):42–49.


Commenting is closed.

The Immunological Microbiome Project: Collaborative Microbial database for the prediction of disease and immunological research

Proposal Status: 

Rationale – The mammalian gastrointestinal (GI) tract contains hundreds of distinct species of commensal microbes under normal conditions, referred to as the ‘microbiota’.  Recently, it has been appreciated that the microbiota exists in a mutualistic relationship with the host immune system. Mutations affecting the production of certain cytokines or resulting in the lack of immune cell subsets are known to increase the overall bacterial burden; however, how underlying immunological conditions influence the colonization of specific species of commensal microbes is poorly understood.  PhyloChip, a recently innovated DNA microarray, is able to rapidly identify over 60,000 microbial taxa in samples of interest.  Using this techonology, we can ascertain the exact effects of diverse immunological phenotypes on the microbiota of the GI tract. Currently, these chips are used extensively at UCSF by the lab of Susan Lynch, though their use has thus far been limited to particular diseases and related environmental studies. We believe that the development of a microbial database encompassing many different immunological states is necessary to better understand the true relationship between GI microbiota and the host immune system. Our first aim is to dissect the unique feature of the ‘microbial profile’ (fluctuation of specific microbial species) in fecal samples obtained from various mouse models of disease including: virus infection, malignancy, arthritis, colitis, asthma, dermatitis and diabetes, as well as genetically modified mice with impairments in immune factors such as cytokines, chemokines, transcription factors and variety of immune receptors (a vast number of them are available in the UCSF mouse inventory). Second, we will compile this information and build the Microbial Database as a web-based open resource for the scientific community. Gathering a microbial profile from each disease state or immunological phenotype will allow us to predict the impact of immune perturbations on the specific make-up of the microbiota and the potential impact on disease.  This project is also an attempt to investigate the potential of PhyloChip as a novel diagnostic and prophylactic tool.       

Plan – We propose following step1 to 3 to accomplish this pilot study.         

Step1 - Standardize the sample collection.  The use of mice provides some stability in terms of mouse to mouse variation.  However, commensal microbiota is very sensitive to age, sex, diet and the environment in each animal facility.  To minimize these confounding effects, we will employ co-housing method.  The mice of interest (designated as tester mice which are genetically modified or disease mice) will be housed in the same cage with control mice (which are wild-type B6 mice raised in our animal facility).  In the case of infectious disease models, tester mice will be orally administered with the feces homogenate collected from control mice before infection.  This method will equilibrate the microbiota in gastrointestinal tract and allow us to dissect the pure influence of specific gene or disease on the colonization of microbial species.  

Step2 - Analyze by PhyloChip.  As a pilot experiment, we will collect fecal samples from 20~30 of the most commonly used genetically-modified mice maintained in our lab or available in UCSF mouse inventory (Rag1-/-, Rag2Il2rg-/-, mMt, b2m-/-, MHCII-/-, Tcra-/-, Tcrg-/-, Lta-/-, Fas-/-, Cd28-/-, Dap10-/-, Dap12-/-, Myd88-/-, Trif-/-, Ifnar1-/-, Il2-/-, Il4-/-, Il6-/-, Il10-/-, Il12rb-/-, Il15-/-, Il17ra-/-, Foxp3-DTR) and major experimental disease models studied in our lab or neighbor labs (Carcinogen-induced tumor, Experimental colitis, Type I diabetes, Listeria infection, Cytomegalovirus infection, Influenza infection, OVA-induced asthma).  All samples will be processed by PhyloChip and we will perform comparative and phylogenetic analysis to reveal the effect of immunity on the all level of microbe’s taxon. 

Step3 - Build pilot database.  All accumulated data will be computationally reconstituted.  We aim to build the data browser with which users can interactively explore the microbiota profile for particular gene or disease. 

Criteria and Metrics for success – 1) Identification of the unique microbial profile in each sample.  2) Launch microbial database.  We will share our data with other researchers all over the world who are interested in the microbiology and immunology, and will accept their feedback and suggestions to improve user-friendliness.  Once these criteria are met, we will move to scale up the size of database.  We will collect samples from another ~50 genetically-modified mouse strains and accept samples from other collaborators.  Ultimately, our approach can be applied into human diseases. 

Estimated cost - We are requesting $40,000 for a pilot study (Step1 and 2).  To build-up public database, we will need $30,000.  For scale-up database, it will need $30,000.

Collaborators - Shoko Iwai (Susan Lynch lab, Dept. of Medicine)

Commenting is closed.

Encouraging research collaboration and integrity by optimizing post-publication peer review for researcher participation

Proposal Status: 


There is an integrity crisis in the life sciences. Since 1990, retraction rates for peer-reviewed medical research have increased by a factor of 4 (Cohol (2007) EMBO 792-3). This crisis highlights how traditional mechanisms of peer review are straining under the ever expanding volume of research being produced.
Post-publication peer review offers a promising solution: researchers could aggregate their opinions online to create an alternative metric of integrity. A number of systems have been built to allow this kind of peer review, but none have succeeded in engaging the research community.


Our team has spent close to a year conducting research in labs on the way that papers are read and discussed, and has created an alternative system which generates significantly more traction. The system is based around figure-by-figure summaries of a paper, soliciting comments on individual figures rather than on papers as a whole.
Initial tests with this system have found extremely promising improvements in both reading time and discussion rates over competing platforms. We are seeking funding to refine the system for launch across and beyond UCSF, and to cover the costs of user engagement.

Criteria and metrics for success

As a web-based application, we will have access to a plethora of data on user behavior. We are seeking to optimize around the following metrics:
 -In order to establish that we becoming a useful part of scientists’ workflows, we will seek to maximize the
number of papers viewed on our system per user per week.
 -In order to establish whether we are serving as a platform for meaningful discussion, we will seek to maximize the number of comments per paper view, and the amount of response (replies and upvotes) per comment.

Approximate cost and very brief justification ($10k-max $100k)

We estimate that launching the project will require a budget of $250k in 2012. The majority of this sum goes to salaries for web development and community management staff. We are seeking $100k to supplement our other sources of funding.


Core team:
Robert Judson- Completing PhD in UCSF BMS program. Focus on complex genetic networks & stem cell biology
David Jay, MBA- Consultant focusing in online community development, web developer.   

Core Advisers:
India Hook-Barnard, PhD- Program Officer, National Academy of Sciences
Keith Yomamato, PhD- Vice Chancellor for Research, UCSF

Commenting is closed.

Using Mobile Technology and Game Dynamics toRecruit and Retain Research Participants

Proposal Status: 

Rationale:  Enrolling subjects for longitudinal research studies, ensuring their compliance and retaining them over a period of time pose a significant challenge to researchers. As an example, we had 62% and 30% retention at years 1 and 3 in a recently concluded study on knee osteoarthritis. To overcome these challenges and to optimize workflow associated with data acquisition, quantification, we have developed a design which combines multiple computing platforms to create a seamless, user-friendly experience for all participants (researcher and subject).  The platforms [using  Ruby on Rails (RoR),  PostgreSQL, iOS  and representational state transfer (RESTful) API]  are designed to enable researchers and subjects to complete data acquisition forms and surveys on tablets which then get quantified and submitted to our cloud servers. Qualitative data show improved subject satisfaction compared to paper forms, reduced paper use by researchers and study coordinators, reduction in man-hours by researchers and study coordinators to manually quantify survey scores and input data into the database and better quality control.

Based on these initial experiences using mobile technology for enhancing subject’s participatory experience and streamlining associated workflow, we propose – (1) the expansion of our current platform to UCSF Imaging clinics (for recruitment and improving care experience), (2)  a one year research study on obese individuals examining effect of weight-loss on knee tissue health using quantitative imaging. This will enable us to analyze the efficacy of the platform towards maintaining compliance and increasing retention. (3) Additionally, we also intend to pilot a networked module incorporating social gaming and feedback principles to assess behavior modification in this population which is of special interest to our lab for our research on knee osteoarthritis prevention.


PLAN:  Recruitment component: (1) Over the 1st three months, enhance the current tablet computer applications to include    interactive versions of intake forms, standardized questionnaires, as well as, modules which simulate the procedure to be performed (MRI, CT, radiography) to address common issues like claustrophobia, restricting movement during scanning etc.. This module will also offer the patients to learn about unique capabilities of the UCSF Imaging centers (safety regulations, metal suppression sequences, quantitative imaging capabilities, other research studies which offer volunteer opportunities) along with a brief bios of the personnel who will be interacting with the patients during their procedures.  While the patients learn about the UCSF imaging capabilities, they will have the option to explore ongoing research participation opportunities  and, if interested, sign up to be contacted by a study coordinator. We have multiple longitudinal trials underway at the moment which will benefit from this mode of recruitment. Possibility of using mHealth frameworks implemented at UCSF will be explored to allow for future adaptability across other UCSF departments. (2) Over months 3-9, administer the tablets to all patients at the UCSF imaging centers (Orthopedic Institute, China Basin Landing and Mission Bay) scheduled for musculoskeletal imaging for clinical or research purposes.

Retention and gaming component: (1) Over months 4-12, twenty-five adult obese subjects from the UCSF- Weight Management Program will be recruited. These subjects will undergo MR imaging at baseline and 6 months, 9 months for quantification of knee tissue health using our standardized metrics. At each time point, subjects will complete surveys related to their levels of physical activity, nutritional data, and incidence of musculoskeletal pain/injuries every month. Additionally, the subjects will complete surveys  remotely using mobile applications (described later) every 6 weeks. (2) Over the 1st three months, develop mobile phone applications for surveys and a “gamified” feature where the research participants can track their scores (levels of physical activity, functional status, pain status, calorie intake) and compare it to other participants, promoting increased participation of physical activity using competitive motivation. A virtual character will be designed (eg: an alien trying to reach home planet) and the participant  will need to complete all study associated tasks, as well as, maintain a certain level of physical activity, consume the recommended diet to enable the character to succeed at the game. Periodically, information on the benefits of the interventions will be incorporated, feedback on the performance with resulting improvements will also be provided and quizzes on weight-management will be incorporated. These approaches have been shown to be effective in management of diabetes, improving physical activity in children and improving walking capacity in adults to cite a few (1-3).

Long term plan: This pilot will be used to demonstrate feasibility, efficacy and flexibility of the platform using UCSF Imaging clinics and research. In the next phase, an NIH application will be submitted for a larger, longer research project where the platform will be implement in obese individuals undergoing surgical and non-surgical weight-loss and followed-up for four years. Eventually, the platform will be made available to all UCSF researchers interested. Recruitment and clinic modules will be made available to other interested UCSF departments immediately. 

Criteria and metrics for success: (1) Percentage of participants enrolled in research studies from the UCSF imaging centers (currently unknown) (2) Clinic patients and research participants will be invited to complete an online survey assessing their satisfaction with their experience, likelihood to stay in the research study and likelihood to return to UCSF for future appointments. (3) Retention in the research studies over a one year period will be compared to retention in all of our other longitudinal studies. (4) Impact of weight-loss on changes in composition of knee articular and meniscal cartilage using quantitative imaging, intramuscular fat content of thigh muscles, levels of physical activity, amount of weight-loss will be assessed at one year.


Approximate Costs and Justification: Total Budget = $95,350; 2 Tablet computers for development @ $400 ea. = $800; 20 Tablet computers for deployment @ $400 ea.    = $8,000; 15% effort from the PD/PI  (Dr. Kumar)  = $8,550; 25% effort from QUIP-C software developer over the year = $25,000; Consultant fees for gamification of the applications =  $25,000; Partial costs for MR imaging of research participants (shared with other grants)  = $28,000


Collaborators:  Deepak Kumar (MQIR); Vivek Swarnakar (QUIP-C), Sharmila Majumdar( MQIR), MQIR), David Dean ( QUIP-C), Richard Souza (MQIR), TBD(Game developer)  



1)      Aoki N, Ohta S, Masuda H, Naito T, Sawai T, Nishida K, Okada T, Oishi M, Iwasawa Y, Toyomasu K, Hira K, Fukui T. Edutainment tools for initial education of type-1 diabetes mellitus: initial diabetes education with fun. Stud Health Technol Inform. 2004;107(Pt 2):855-9.     

2)      Southard DR, Southard BH. Promoting physical activity in children with MetaKenkoh. Clin Invest Med. 2006. 29(5):293-7.

3)      Consolvo S, Everitt K, Smith I, Landay JA. Design requirements for technologies that encourage physical activity. In: Grinter R, Rodden T, Aoki P, Cutrell E, Jeffries R, Olson G, editors. Proceedings of the SIGCHI Conference on Human Factors in Computing Systems; 2006 Apr 22-27; Montreal, Quebec, Canada. New York: ACM; 2006. p. 457-66.

Commenting is closed.

Column kit for analytical method development

Proposal Status: 

As a core pharmacology laboratory for Center for AIDS Research at UCSF, the Drug Research Unit (DRU) often encounters problems regarding column selection during memthod development. Here I propose to seek for funding to buy 25-50 analytical columns as a column kit for method development.

Background (Rationale): Drug quantification requires optimal separation to achieve high selectivity and specificity. Different drugs may require different columns to achieve optimal separation and quantification. For a new method development, we generally choose a column used for existing assays at DRU, or based on similar methods from literature, which we often find are not the best choice, as most laboratories like ours may only have a limited number of analytical columns tested for method development. Here I proposed to purchase a set of columns covering different separation mechanism and column dimension. A general summary of different columns is listed as follows:

  1. Reverse phase columns: C2, C4, C8, and C18 columns.
  2. Normal phase and HILIC columns: un-derivatized silica-, amide-, diol-, cyanopropyl-, aminopropyl-, zwitterionic sulfoalkylbetaine-based columns.
  3. Hypercarb column: based on carbon graphite, retention mechanism is different from reverse phase columns and HILIC columns, and show good retention time for polar compounds.
  4. Ion exchange columns.
  5. Monolithic columns: Chromolith™ SpeedROD RP-18e.

Analytical columns have different particle size (1.8, 2.7, 3, and 5 μm). Particularly sub-2 μm columns are used for the UPLC system recently acquired by DRU through a RAP CTSI-SOS shared instrument award. Fused-core columns having particle size of 2.7 μm are suitable for the LC system coupled with the API5000. Columns with 3 and 5 μm particles can be used in all LC systems in DRU.

Analytical columns have different dimensions (2.1x50, 2,1x100, 2,1x150, 3x150, 4.6x50, 4.6x150). I proposed to acquire two dimensions for each type of column: 2.1x50 mm and 2.1x150 mm.

Plan of use: The DRU does not have the resource to buy a full range of different columns. If we can get fund to buy a column kit, it will benefit DRU and our collaborators at UCSF greatly. This column kit is only used for the purpose of column selection during early stage of method development. Only drugs in clean solvent will be applied to those columns. Once a column was identified for a new assay, the same column will be purchased for the later stage of assay development. Therefore, the column kit can be repeatedly used for any new assay development. The newly acquired UPLC system is open to co-investigators and others at UCSF on Monday and Friday. They can also use the column kits to develop methods. This is especially useful for them because analytical columns in non-analytical labs are very limited. It is not worth buying a new column if only a small number of samples are analyzed.

Budget: each column costs $400-700, average $550, we seek for $25,000 to secure a variety of columns for method development.

Collaborators: Collaborators (B. Joseph Guglielmo, Sunil Parikh, Katherine Yang, and Janel Long-boyle) and investigators who will use our core facilities.

Commenting is closed.

Developing an administrative data system to investigate the social and health impacts of early childhood programs in San Francisco

Proposal Status: 

Rational: There is extensive evidence of pervasive social disparities in health, many of which take root in early life. The importance of early childhood in setting the stage for future health and social outcomes is buttressed by rigorous scientific studies across disciplines. However, what remains less investigated is how well this knowledge has been translated to public agencies responsible for implementing early childhood programs and family support services. The Department of Children Youth and their Families (DCYF) in San Francisco is one of the few departments in the country dedicated exclusively to meeting the needs of young people, and has made extensive investments in child physical and mental health programming and family support services (over 11 million dollars in 2010). However, the effectiveness of these programs in influencing key social, mental and physical health outcomes has not been investigated.  Through a collaborative effort of UCSF researchers, the San Francisco Mayor’s Office, the Department of Children Youth and their Families (DCYF), the San Francisco Department of Public Health (SFDPH), and the San Francisco Unified School District (SFUSD), we propose to develop a linked administrative data system that will allow us to track and evaluate the impact of early childhood programming and family support services on academic achievement, and mental and physical health.

Plan: We propose to develop a data linkage between the DCYF and SFUSD systems, with the goal that this linkage will be generalizable to other agencies serving youth in San Francisco.  The goals for this proposal are to 1) assess similarities and differences in existing data structures used by DCYF and SFUSD, 2) address confidentiality issues related to establishing a linked data system in San Francisco, and 3) select and test linkage variables that will uniquely identify individual level information across DCYF and SFUSD datasets. Dr. Kaja LeWinn, a social epidemiologist in the Department of Psychiatry, will play a key role in this effort. Dr. LeWinn has spent the last two years working closely with SFUSD, has developed an intimate knowledge of the school-based services provided by DCYF and existing tracking systems, and has established relationships with key partners.  To accomplish our goals, our group with meet every other month for the duration of the award and Dr. LeWinn will meet individually with specific members as necessary.

Criteria and Metrics of Successes: At the end of this pilot project year, we will have developed a reliable linkage between the DCYF and SFUSD data systems, and submitted an application for grant support to further develop and implement this system.

Cost: We ask for $20,000 to provide salary support for Dr. LeWinn so she may dedicate research time to further developing this project and relationships with key public sector collaborators.

Collaborators: Our collaboration is united around the common vision that physical and mental health disparities begin early in life, and that a longitudinal, linked data system that tracks the usage and effectiveness of publically available programs will be an instrumental resource for both researchers and public policy makers. Key public sector collaborators and supporters include: the Mayor’s Office (represented by Hydra Mendoza); Richard Carranza, Deputy Superintendent for Instruction, Innovation and Social Justice, SFUSD; Maria Su, Director of the Department of Children Youth and Their Families; and Ritu Khanna, Assistant Superintendent, Research Planning and Accountability, SFUSD. Dr. LeWinn will play a key role in maintaining this partnership in collaboration with Orlando Elizondo, Director of the SFUSD/UCSF Partnership.  

Commenting is closed.

Mobile Study Support Pilot Project

Proposal Status: 

Rationale: UCSF and the Benioff Children's Hospital have been selected by the national Children's Oncology Group Consortium (COG) of the National Cancer Institute (NCI) to conduct new Phase I Pediatric Oncology studies. Patients enrolled in these studies who are not admitted to the Pediatric Clinical Research Center (PCRC) Inpatient Unit, will require evening and weekend support for study procedures, including timed blood draws, sample processing and EKGs. We propose a “Mobile Study Support” (MSS) Pilot, under the CTSI/Clinical Research Services-PCRC to improve the conduct of translational research. MSS services would assist in providing research procedural care to oncology inpatients participating in clinical trials on the 7-Long Oncology Floor, as well as other UCSF investigator studies. We anticipate the MSS model will become widely utilized as we transition to our new pediatric hospital at Mission Bay.

Plan: A PCRC research nurse, 60% FTE, will become an Administrative Nurse (AN) I and will increase her effort to 90%, to include MSS nursing, PCRC outpatient unit clinical care, and administrative duties. The nurse in this position will be familiar with related study procedures, since procedures for Oncology protocols to be supported, mirror the 70 current active research studies in the CTSI/CRS-PCRC. Immediate benefits of this pilot are continuity with knowledge of investigator studies and teams, clinical research nursing expertise to these teams, and expert care to patients participating in these phase I trials. The new AN I position of the MSS PIlot is an innovative role that will add value to the growing demand for pediatric Outpatient and mobile visits. Because this position contains an administrative component, the hours will be flexible to meet the demands of the clinical care and administrative needs without requiring to pay for on call time for mobile visits. The MSS pilot design will dedicate maximal effort to protocols approved under the COG Consortium while accommodating variability in protocol volume as this new service line grows. Sustainability will be measured by the increase in investigators supported and the expansion of site locations beyond the Benioff oncology unit on 7 Long. (see collaborators below). Six active Oncology studies are requesting immediate support: ADVL0912, ADVL1112, ADVL1013, ADVL1011, ADVL0921, NANT0702. Three additional, new leukemia phase 1 studies in various stages of development are also strong candidates: AALL1121, ADVL1114, TACL0903.

Criteria and metrics for success: Measures of success will include number of studies, number of patient locations, number of patients served, patient contact hours, investigator satisfaction with nursing and study support, and cost per patient vs. alternative costs (such as admission to PCRC beds). Challenges and barriers to success will be presented to the CTSI CRS leadership to improve the pilot design. Funding contributions to support this pilot will be sought from investigator grants to ensure the pilot's success and sustainability. Alignment with CTSI Strategic Goals includes responsiveness to; 1) "CRS-without-walls" model to increasingly support investigators outside the current eight CRS sites, 2) Creating cross-cutting initiatives with consortium partners, thus increasing new and potential collaborations to accelerate research, 3) Work with CTSI's Program Evaluation Unit to apply dashboard/metrics methods to monitor and report on progress. This MSS Pilot can also serve as a model for the national COG-NCI group, other CTSA sites, and is in alignment with the model of the National Center for Advancing Translational Sciences (NCATS/NIH).

Cost and sustainability: Administrative Nurse I salary and benefits at 60% are as follows:

$147,394 (salary base) x 60% (effort) = $88,438 (salary) + $20,438 (benefits) = $108,876. $100K is requested for this pilot. After initial start-up cost, cost recovery is anticipated for services to offset 20-30% costs in YR1, with further increases in out years. As MSS demand increases, service providers other than RNs may be included to perform research procedures not requiring RNs, such as performing EKGs and processing specimens during non-business hours.

Collaborators: NCI Children’s Oncology Group (UCSF investigators Drs. Kate Matthay, Steven DuBois, Robert Goldsby, and others), UCSF Intensive Care Unit Research Team, UCSF Cancer Center, UCSF Benioff Children’s Hospital at Mission Bay.

Commenting is closed.

“Idea to Impact” (i2i): Translational Digital Health Program

Proposal Status: 

Rationale: The rapidly evolving field of digital health has great potential to enhance biomedical research, education and clinical care. Development in this new space is largely being driven by the tech sector, where projects may lack proper clinical focus or scientific rigor and generally do not include health outcome measures to assess effectiveness or impact. UCSF can play a vital role in ensuring that digital health ideas are appropriately targeted to real clinical problems and that they result in meaningful impact, by improving health, improving care, and lowering costs. We propose the i2i Translational Digital Health Program to foster UCSF and industry collaborations to initiate, develop, and test impactful and cost-effective digital technology to improve biomedical research, education, and clinical care.

Plan: This i2i proposal is to identify and develop the critical resources and programs necessary to facilitate and accelerate the “idea to impact” trajectory for digital health innovators both within and outside UCSF, in a multidisciplinary way that combines sound scientific methods with technology, design, business strategy, fundraising, IP, regulatory and marketing expertise. This first year of i2i will focus on the following:

  1. Establish a focal point for CTSI Digital Health initiatives, with multidisciplinary internal/external partners
    • Create an intersection for collaboration between UCSF Digital Health initiatives (e.g., BMI, ISU, QB3, ITA, SOM, Institute for Reducing Health Care Costs and other innovative efforts at UCSF).
    • Create strong UCSF presence in Digital Health to external partners, working with Virtual Home on a website, with campus on social media, with Development officer, etc.
    • Explore and establish external partnerships (e.g., UCs, CITRIS, investors, companies, public health).
    • Host Annual UCSF Digital Health Summit: to showcase “ideas” and “impacts,” convene partners
  2. Identify and implement needed processes and resources for accelerating “idea to impact”for the main types of digital health projects, e.g., projects aiming for a) internal (e.g., RAP) and external grants; b) operational deployment to improve health locally to globally; and c) commercialization. We will:
    • Convene a series of meetings with faculty/trainees, staff, and various external partners (e.g., investors, tech companies, start-up incubators, design firms, etc.) to define hurdles, needs, objectives
    • Work with ITA and other groups to define models for supporting each type of project, and implement initial steps with FAQs, standard agreements, etc. as appropriate
  3. Build a vibrant and supportive Digital Health i2i community
    • Establish an external Digital Health consultant panel, modeled after T1 Catalyst, to serve as consultants to UCSF, grant reviewers on RAP proposals, i2i Advisors, etc., with networking events
    • Establish an internal consultant panel of research, clinical, education, technology, and informatics experts to serve as consultants grant reviewers, Services, i2i Advisors
    • i2i Web presence - with Virtual Home, enhance UCSF Profiles (digital health keywords), Digital Heath Innovators Forum, links to useful collaboration tools, survey needed resources, crowdsourcing i2i tips
    • Quarterly or bi-monthly multidisciplinary “Eye to Eye” roundtables featuring specific research or clinical “problems” and potential digital “solutions,” presented to an audience of External and Internal Panel members, to foster relationships and potentially ignite Digital Health projects.
  4. Define and implement recharge and IP models for internal and external consultation We will work with Consultation Services, ETR, ITA, etc. to adapt and develop processes for UCSF faculty consulting to industry, for industry consulting to faculty/staff, and for staff (e.g., ISU, ITA) consulting to faculty

Criteria and Metrics of Success: digital health website with communications plan and metrics; defined internal pathway/processes for idea transfer; implemented recharge mechanism for Consultation Services; 20 external consultants panel members, from range of disciplines and public/private; 15 internal consultants panel members; Annual Summit, 4 “Eye to Eye” events; 2 new external partnerships

Cost and justification: Staff support 0.4 FTE $40,000K; website and communications: $20K; Symposium and “Eye to Eye” roundtables: $10,000 with sponsorships to defray; external consultants panel $5,000.

Total: $75,000. The sustainability model will include recharge, shared royalty/licensing programs, partnerships with clinical enterprise/external groups, UCSF Digital Health Consulting Panel (to external parties), and philanthropy, with self-sustainability anticipated in 3 years.

Collaborators: Sim/Sawyer (BMI), Lee (ETR), Pletcher (CS), Yuan (Virtual Home), Lium (ITA), Melese (SOM), Crawford (QB3), Jorgenson (ISU)

Commenting is closed.

A Digital Clinical Research Center (dCRC) for Translation of Digital Health Interventions

Proposal Status: 

Rationale: The confluence of online social media, smart phones, and sensor technology is giving rise to a tidal wave of digital health interventions that have vast potential for improving health at low cost. As with consumer software, digital interventions are more likely to be effective if user feedback and determination of effectiveness is sought early and often. At present, however, researchers face high costs and difficulty in developing app ideas into prototypes, testing prototypes on real users, and validating the intervention. These difficulties are a significant barrier to securing extramural funds, and to the translation of digital health technology into population health. The challenge the dCRC addresses is to reduce the expense, time, and expertise required to prototype and validate digital health interventions.

Plan: The long-term goal of the dCRC is to support the full range of digital health intervention research, from early prototype development to pilots to large scale RCTs. In this first year, we will focus on a large class of projects that we are seeing in CS, BMI, and CRC: projects that want to 1) collect and analyze sensor-derived actigraphy and geolocation data, and 2) leverage online social networks (from Facebook, in particular) for recruitment and for delivery of novel network-related interventions. These project needs require new methods for data collection, analysis, visualization and feedback to patients, and confront investigators with a variety of barriers (technical, design, ethical). It is inefficient for each team to pull together the multidisciplinary expertise needed to surmount these barriers. To meet this challenge, we propose to create a Digital Clinical Research Center (dCRC), housed within CRS in collaboration with BMI, CS, and ETR, that will support development and translation of novel digital health interventions by:

  1. Providing re-usable software modules for data collection and analysis. Through a combination of UCSF-led development and access to open software from Open mHealth (Co-Founder Sim), we will provide researchers with standard modules for collection, analysis, and visualization of:
    • Actigraphy and geolocation data collected via smartphone and other sensor devices
    • Online social network data from Facebook.com collected via “Facebook Connect”. Modules will facilitate feedback/visualization of intra- and inter-network health comparisons. (Based on prior work by The Social Heart Study, PIs Pletcher and Fowler]).
    • An initial set of self-reported demographics and health-related behaviors including exercise, diet and sleep collected via mobile devices. Our efforts will align with and contribute to NIH’s PROMIS and PhenX projects, which aim to standardize clinical research data collection methods.
  2. Recruit a standing dCRC cohort interested in digital health interventions. PRS will lead online recruitment of at least 2,000 broadly representative participants interested in testing new health technology and undergoing some or all of the measurements detailed above.
  3. Develop CRC-type procedures for using the dCRC cohort. Using standard CRC’s as a model, we will develop an application, review process, protocol development support (via CS) and a recharge for UCSF and outside investigators (including industry) interested in using the dCRC cohort for early (pilot) and late stage (validation) testing of digital health interventions.
  4. Develop ETR-type resources for commercializing validated digital health interventions. ETR will develop matchmaking, IP consultation and other resources to support academic investigators interested in licensing or otherwise commercializing their products.

The dCRC will drastically reduce the marginal costs and expertise required to translate good digital health intervention ideas into products that improve population health. This service is highly relevant to industrial interests, and we expect that revenue generated from allowing industrial access to the dCRC will eventually support core services and highly subsidize costs for UCSF and other academic investigators.

Criteria and Metrics of Success: 5000 participants recruited (500 by end of Year 1); 10 new re-usable data collection/processing modules, in addition to modules available through Open mHealth; 5 projects using dCRC modules in their technology; 2 projects using the dCRC cohort; a recharge mechanism and a dCRC application and review process in place.

Cost and justification: $40K in programming costs, $10K for recruitment, $50,000 for 0.5 staff FTE = $100,000 total. We expect initial recharged projects early in FY08, and self-sustainability within 3 years.

Collaborators: I. Sim (BMI, Open mHealth); M. Pletcher (CS); B. Balke, N. Nasser (CRS); J. Lee (ETR); J Fowler (UCSD); J. Olgin (UCSF Chief of Cardiology); and T. Parsnick (SF Coordinating Center)

Commenting is closed.

IT Improvements Needed to Make APEX useful for Clinical Research

Proposal Status: 

Rationale: The APEX system has been promoted to the faculty as providing a new and extremely valuable means of doing clinical research, especially for discovering previously unappreciated clinical associations such as the relationship of kidney stone and myocardial infarction, etc..  Such associations would be very valuable in discovering underlying mechanisms of disease.  However, the APEX system falls very short of fulfilling this promise, because it has been primarily designed for maintaining information for medical practice, and for billing.  The problem is that it forces the physician to use vague descriptors of disease that are so imprecise as to be of no value whatever in discovery of associations.  For example in our Lipid Clinic we have discovered a form of dyslipidemia, cholesterol 7 alpha hydroxylase deficiency, that we believe afflicts about 100,000 Americans.  The APEX system refuses to allow us to enter this diagnosis for search purposes, insisting on “cholesterol problem” as a substitute.  Because there are probably fifty individual diagnoses that could fall under this heading, all value to translational research is lost.

Also there are data from emerging biomarkers, etc. that it will not accept for search processes. An example is the biomarker, prebeta-1 HDL, also discovered by our group, which is emerging as a robust indicator of risk of myocardial infarction. We have measured this biomarker on nearly four thousand patients.  We should be able to enter it  with  the restriction that it cannot be used for clinical decision making, but allowing faculty to access its value for clinical research.

An academician from the Cleveland Clinic, lecturing here recently, stated they also found APEX nearly useless for research, leading them to re-engineer the IT to overcome these issues, making detailed information searchable.  This was done carefully within the envelope of APEX without altering its function for clinical practice, billing, etc.

Plan: We would bring in expert IT personnel to make the changes in APEX, fitting it to our particular needs and system characteristics at UCSF.  We would support part-time effort of a clinical faculty member to supervise the entry of appropriate descriptors, following the experience at the Cleveland Clinic.

Criteria and Metric:

We can test the system for association of descriptors in widely diverse information fields.

Approximate cost:

Expert IT consultation and engineering $40K

Faculty time for descriptors: $ 15K

Collaborators:  Faculty from diverse disciplines would be welcomed to bring precision to the descriptors in their respective fields.

Commenting is closed.

Research Networking Software App/Gadget Development Competition

Proposal Status: 

Background/Rationale: Social networking sites such as Facebook, Google+ and LinkedIn are web platforms. They allow independent applications to run within their sites to enhance the user experience, often integrating with external services to provide dynamic content as varied as reading lists from Amazon, blog posts from WordPress, to live game play from Zynga. The beauty of these external services is that they can be shared across any software platform that chooses to deploy them.

At UCSF, we recognized the value in making our research networking tool into a web platform. Accordingly, we have contributed an extension to the open-source Profiles research networking software tool, and we are now using our UCSF Profiles installation as a platform (based on the industry standard OpenSocial), whereby we have written "apps" or "gadgets" to extend the functionality. One such gadget is to display presentations, posters and other content that is uploaded to Slideshare.net, within an individual's UCSF Profile page itself. This gadget allows researchers to share conference presentations, lectures etc. easily within their UCSF research profile.

The software code for these gadgets is open source; gadgets can and have been shared with other institutions. The end goal is to create an open library of shareable gadgets for research networking, where any institution (academic, for profit etc.) can contribute to or use the apps in this library.

At this point, we think research networking software tools could make a giant leap forward by harnessing this simple technological implementation and marrying it with many institutions’ knowledge of what features and functions will enable more efficiency and collaboration in the research process. To date, one other institution using Profiles has adopted the standard and another is on track to do so in a matter of months. Wake Forest has successfully deployed Profiles as an OpenSocial enabled platform and has written 2 of their own gadgets. Baylor is now on track to do the same.

Plan: We propose to hold a competition similar to one held by VIVO in 2011. A call to institutions for the best ideas for research networking software functions would be sent out and judged on a set of criteria that would include feasibility, value and impact for enabling research efficiency and/or collaboration.

We will choose 2 winners of the competition and each would receive:

  1. A new iPad 
  2. Plus, development of the gadget itself, using resources from the VH team and our development network to execute. Winner would be acknowledged in attribution on gadget itself once launched.
  3. Recognition via public presentation(s) at Profiles User Group meetings, as invited guest presenter at CTSA IKFC meetings etc.

With the following stipulations: a) the resulting gadget is offered in the library and made available free and open-source, 2) the winner is available as needed as subject matter expert during design and implementation of the gadget.


Impact/Value: We believe this project:

  • will further the ability for research networking tools to have impact on the research process
  • will contribute to the national CTSA body of knowledge and experience with research networking
  • allow institutions and individuals with creative ideas for features to share those ideas with the community and contribute in a timely manner
  • further demonstrate that OpenSocial is an inexpensive way to create valuable production level apps given the low technical complexity of gadgets.

Criteria: Criteria for entry would be open to all, but with active promotion to UCSF, all institutions in the Profiles User Group, all VIVO-enabled institutions.  Judges for entries would be identified from the CTSI VH team, CTSI leaders / faculty, and institutions currently leading the research networking software field (e.g., Harvard, and Wake Forest)


While we know that we may get ideas easily from IT folks, we will make a concerted effort to gather ideas from researchers themselves. In addition to soliciting the CTSI faculty (for their own ideas in addition to recommendations for others to contact), we will target those faculty who:


1)      commented on our open proposal

2)      have very well fleshed out profiles on UCSF Profiles

3)      are engaged in science of team science (we will use UCSF Profiles to identify these peopleJ)

4)      have been past proponents of UCSF Profiles

5)      have been interviewed personally by VH team members (Research Networking 2.0 interviews)

6)      are part of our post-doc user group. 


We will create a detailed description for the call for ideas. This will include the scope, i.e., new features specifically for research networking software products, and the judging criteria (to include feasibility, applicability to OpenSocial approach, value and impactfor enabling research efficiency and/or collaboration). In addition, while we plan to promote actively at UCSF, we’ll solicit entries outside of UCSF by leveraging our relationships with other institutions that are heavily engaged in adopting research networking software tools, such as the Profiles User group (including Harvard, Wake Forest, Baylor, Minnesota), Stanford CAP, VIVO (including U Illinois, U Florida), U Iowa LOKI, and the CTSA IKFC National Research Networking Group.



Total Budget: $33,406

$1000 for iPads, $32,406 for development and project management of 2 gadgets

Collaborators: Wake Forest, Harvard, CTSI leadership / faculty as judges.

Commenting is closed.

$15,000 a dose: A patient-centered study of drug development and research

Proposal Status: 

Title: $15,000 a dose: A patient-centered study of drug development and research

Rationale: The United States spends $100 billion annually on cancer care, with the majority of costs connected to drug development and technological advances.1 Several researchers have raised concern that the cost of cancer care will continue to rise until it becomes unsustainable.1,2 One strategy for addressing the rising treatment costs is to consider cost when planning clinical trials. Value-of-information theory (VOI), commonly used in economic and decision science settings, is one example of a method to address this issue. Applied to clinical trials, VOI theory could help determine which trials should be funded by considering a combination of factors such as drug price, cost of the trial, and duration of treatment.3 Using this theory, a drug that is projected to offer only similar clinical benefit – such as progression-free survival – as another but is more costly would not be selected for trial funding.

While VOI highlights how consideration of cost is needed at the development phase, we believe that patients have a role to play in this phase as well.4 Currently, no studies to date assess patients’ perspectives about the escalating cost of treatment and the implications for drug development, giving rise to a challenge in the design and conduct of clinical research. High treatment costs have resulted in increased cost-sharing with patients through higher premiums, co-pays, and deductibles. Since patients bear more of the burden of paying for these cancer treatments, it is critical that their perspective is taken into account early in the drug development phase. For example, it is important to know how patients feel about the development of highly expensive drugs that would 1) contribute to the societal burden of increasing health care costs, and 2) likely be too expensive for the majority of patients in the era of increased cost-sharing. It has been suggested that what patients really want from health care (i.e. timeliness, hope, and certainty with no interest in the real cost of treatment or the percent GNP devoted to health care) is often “irrational and unrealistic.”5 We feel that patients must first be presented with information about actual treatment costs and the process of drug pricing, and only then can they be expected to consider the trade-offs of health care decisions as informed, rationale consumers.

Plan: We will conduct a pilot project that will survey and interview patients at the UCSF Breast Care Center about their perspectives on the cost of cancer care and drug development in relation to clinical research. The aim of the study will be to design a patient-centered framework for approaching costs within the context of clinical research. We will recruit a diverse group of participants, including women who are and are not currently enrolled in clinical trials, women with and without a prior cancer diagnosis, and women in diverse socioeconomic, age, and ethnic groups. Participants will be presented with simple scenarios that illustrate the critical issues about drug costs and insurance coverage rates, and how clinical research can influences these issues. These scenarios will be designed with the advice of Celia Kaplan, DrPH, an expert in qualitative methods, using language and terms understandable to the average patient. Participants will be surveyed to understand patient perspectives on the following: 1) trends in cancer treatment costs, 2) implications of cost-sharing (co-pays, high deductibles) on drug development and research, 3) the process of drug pricing, and 4) opinion of using VOI methodology in the early phase of drug development. We plan to frame some of our analysis according to participants’ responses to certain ethical questions such as who should determine how money is spent in health care and how “irrational and unrealistic” preferences should be considered.

This study is “shovel-ready” – the investigative team has worked together on similar projects in this clinical setting and these participant groups, and has patient surveys and IRB protocols ready for submission once funding is secured.

Criteria and Metrics for Success: From the responses and data gathered from this study, a framework for approaching costs within the context of clinical research will be developed.  Specifically, the pilot study will be a success if the study can determine the following: 1) patient views regarding VOI methodology for use in drug development, and 2) guiding principles around patient treatments costs and clinical research.

The broader implications of the study will guide more selective funding of clinical trials (such as through VOI) or a reassessment of these selection methods that considers patients’ perspectives on the cost of cancer care and drug development. The investigators have the unique opportunity to implement the findings of this study in the UCSF Athena Breast Health Network, an innovative collaboration across the 5 University of California medical centers that is integrating clinical care and research to drive innovation in prevention, screening, treatment and management of breast cancer. Our study will develop the knowledge base required to establish a scalable and sustainable approach to the conduct of research in a novel clinical care and research cohort such as Athena. Elissa Ozanne, the study PI, is the Director of Risk Assessment and Decision Science for Athena, and Laura Esserman, a study collaborator, is the PI for the UC-wide Athena Network. Together, these study investigators will design the study such that results can be directly applied to ongoing and future Athena research efforts.

Cost and justification: The anticipated costs are $25,100 to support 1) 5% effort ($10,800) for the PI (Elissa Ozanne, PhD), 2) a clinical trial coordinator (Rebecca Howe) at 20% of her effort ($9,800), 3) patient recruitment and survey costs ($2,800), 4) data analysis costs ($1,200), and 5) supplies ($500).

Collaborators: Elissa Ozanne, PhD (UCSF – Department of Surgery, Institute for Health Policy Studies), Michael Hassett, MD (Harvard Medical School), Rebecca Howe (UCSF – Department of Surgery, Institute for Health Policy Studies), Lisa Bero, PhD (UCSF – Department of Clinical Pharmacy), Michael Alvarado, MD (UCSF – Department of Surgery), Laura Esserman, MD, MBA (UCSF – Department of Surgery, PI of Athena), Celia Kaplan, DrPH (UCSF – Department of Medicine)


  1. Meropol NJ, Schrag D, Smith TJ, et al: American Society of Clinical Oncology guidance statement: The cost of cancer care. J Clin Oncol 27:2868-3874, 2009
  2. McFarlane J, Riggins J, Smith TJ: SPIKE$: A six-step protocol for delivering bad news about the cost of medical care. J Clin Oncol 26:4200-4204, 2008
  3. Schmidt C: Researchers Consider Value-of-Information Theory for Selecting Trials. J Natl Cancer Inst 102(3):144-146, 2010
  4. Fleck LM: The costs of caring: Who pays? Who profits? Who panders? Hastings Cent Rep 36(3):13-17, 2006
  5. Detsky AS: What patients really want from health care. JAMA 306(22):2500-2501, 2011

Commenting is closed.

Broadband Multichannel Transmitters for Enhanced Metabolic MR Imaging

Proposal Status: 

1. Rationale

Surbeck Laboratory for advanced imaging at UCSF, is an interdepartmental and interdisciplinary laboratory that provides unique instrumentation, expertise, and infrastructure to enable the faculty, trainees and staff to carry out translational and clinical research utilizing the unique capabilities of high magnetic fields. Research at the Surbeck Lab has resulted in some of the most advanced MR instrumentation and expertise currently available and has been the source of critical technologies and methodologies in multiple areas of non-invasive biomedical research at cellular and molecular scale.

With quantitative capability, magnetic resonance imaging and spectroscopy (MRI/MRS) have become a promising non-invasive imaging modality for biomedical research. This application seeks funding to enhance our quantitative imaging capability through development of broadband multichannel transmitters on the high-end whole body MR imaging systems. Currently our MR systems at Surbeck Lab are equipped with only 1 transmit channel. It has significantly limited the capability of imaging and restricted its applications to conventionally slow and outdated approaches. The proposed development will enable the advanced imaging technologies on our UCSF MR systems and significantly improve our research infrastructure. With the multiple transmitters, parallel imaging techniques with fast selective excitation and B1 shimming can be used to dramatically accelerate the imaging speed, improve imaging sensitivity and reduce sample heating. This will be a shared instrumentation and would significantly benefit a wide range of biomedical research in a qualitative fashion and facilitate translational and clinical research projects within UCSF community. This development could give our quantitative imaging resource a quantum leap and move imaging capability of UCSF to the forefront of the field. This is not about a local competition, but rather about making UCSF a world leader in in-vivo MRI/MRS methodology and its medical, biological and pharmaceutical research applications. This would be an invaluable asset which benefits the whole UCSF community tangibly.  

2. Plan

This project will be accomplished via the following three steps.

a) Design and construction of broadband 16-channel transmitter system with capabilities of high transmit power, independent amplitude and phase control, and independent RF pulse waveform generation. This system allows for parallel transmit, B1 field shimming and increased MR sensitivity, consequently resulting in high sensitivity, high temporal resolution, uniform image, and reduced tissue heating; The broadband capability enables multi-nuclear and multi-field-strength MR imaging.   

b) Development of user-friendly interface software and integration of the proposed multi-channel broadband transmitters to the GE MR control software, ensuring the compatibility with the GE MR console;

c)  Broadband transmitter installation, testing, validation, and safety assessment on 3T and 7T systems.

3. Criteria and metrics for success

The proposed multichannel transmitters will be tested on bench. Each transmitter channel should have a frequency range of 120MHz to 300MHz, a phase range of -200 to 3800. RF power attenuation should be able to control the output from 30dB to 5dB with max 200W output. MR imaging experiments validation will be performed on the 3T and 7T MR imaging systems housed on UCSF Mission bay campus. In MR imaging experiments, the overall B1 field pattern can be controlled by changing RF amplitude and phase of each transmitter channel. Improved MR sensitivity and reduced SAR should be observed.  

4. Approximate cost and very brief justification ($10k-max $100k)

We request budget to buy required electronic parts for constructing the proposed multi-channel transmitters, including capacitors, inductors, phase shifters, attenuators, mixers, coaxial cables, RF connectors, and also circuit board manufacturing, etc ($35,000); General lab supplies for constructing and testing the transmitters ($10,000); MR scans for performance validation (10 hours x $500/hr = $5,000); 15% effort of the PI (Xiaoliang Zhang, PhD) who will be responsible for the administration and direction of the project, also aid in designing, constructing, testing, and validating the proposed transmitters, help in equipment installation and hardware/software integration, and assist in the data analysis and interpretation ($21,750). 30% effort of an engineer (Yong Pang, PhD) ($13,500). This person will design the transmitter circuits and required software for user-friendly interface to control the transmitters; Total direct costs requested: $85,250.

5. Collaborators

Collaborators of our research lab include Daniel Vigneron, PhD; Sarah Nelson, PhD; Sharmila Majundar, PhD; Christopher Hess, MD; Xiaojuan Li, PhD; David Wilson, MD; Duan Xu, PhD; Orit Glenn, MD; John Kurhanewicz, PhD; Jin Liu, PhD; Sabrina Ronen, PhD, Pedar Larson, PhD; Roland Kruger, PhD

Commenting is closed.