To evaluate whether an online engagement platform for chronic hives / urticaria (CU) accessible to diverse patient populations and focused on symptom tracking, assessment of psychiatric comorbidities, and clinician feedback improves immediate and long-term CU symptom control.
Background and Problem
Urticaria or hives is a common affliction that affects 25% of the general population. A subset of patients with urticaria develop chronic urticaria (CU), which has an estimated prevalence of 0.5-5% and incidence of 1.4% per year in the general population and is characterized by recurrent pruritic hives and/or painful angioedema for six weeks or more. The biology of CU is not well-understood, although a subset of patients may have an autoimmune basis to their CU.
CU has a significant detrimental impact on quality of life as CU disrupts patients’ activities of daily living, work, and sleep. Indeed, one-third to one-half of CU patients experience depression and anxiety, and the health status of CU patients is comparable to coronary artery disease patients awaiting bypass surgery. Many patients do not receive adequate psychosocial care.
Achieving symptom control during the first year after CU onset is recommended, as data suggest that early symptom control is associated with improved long-term symptom control. Unfortunately, despite the fact that there are effective CU therapies available, achieving early symptom control remains one of the biggest challenges in CU.
Cultural and linguistic barriers prevent patients from receiving the frequent clinician feedback needed for symptom assessment and treatment. Another significant barrier to achieving early symptom control is inadequate access to allergists. Patients report 3-6 month wait times to be seen at allergy clinics (UCSF, other academic centers, and private practices). This wait period encroaches on that early time period when achieving symptom control is critical. After patients have been seen by an allergist, distance can prevent patients from receiving the frequent follow-up needed for symptom assessment and treatment.
An online engagement platform with symptom tracking and clinician feedback would address the major barriers to adequate care – distance, cultural and linguistic barriers, and insufficient access to allergists. It would allow allergists to manage a diverse population of patients remotely and enable early symptom control critical for long-term treatment success. Existing apps created through the American College of Dermatology, Genentech/Novartis, and eResearchTechnology are only available in English and are not adequate for meaningful patient follow-up.
One emphasis will be on creating a platform with a culturally and linguistically appropriate design such that non-English-speaking patients from diverse cultural backgrounds can be included in the study cohort. We will start by conceptualizing the initial platform design with existing symptom and quality-of-life measurement tools that have been translated into Chinese and Spanish and have been validated in Chinese and Latin@ populations. From there, we plan to use semi-structured interviews of chronic hive patients in our clinics (initially English-speaking and Chinese-speaking) to guide platform design so that it is tailored to cultural and linguistic needs. If our initial pilot studies are successful, our plan is to expand the platform to include culturally and linguistically appropriate tools for Spanish-speaking Latin@ patients. In this way, we hope to potentially adapt existing symptom and quality-of-life measurement tools to culturally diverse populations.
Our proposed platform and studies would assess the cultural appropriateness of smartphone-based health data and best strategies for patient engagement across diverse populations.
A CU cohort lends itself well to this type of platform.
- There are well-validated tools to measure symptoms. The Urticaria Activity Score (UAS-7) and Itch Severity Scale (ISS) are recommended for use in routine practice and in clinical trials to measure disease severity. Symptom tracking allows patients to better identify non-allergic triggers and specific physical triggers, which affect 25% of patients with CU.
- There are validated quality of life tools such as the Chronic Urticaria Quality of Life Questionnaire (CU-Q2OL) and Dermatology Life Quality Index (DLQI).
- CU therapies are known to be effective in up to 97% of patients, and the main difficulty with symptom control is access to care and adequate follow-up. Therefore, an online platform that enables early access and frequent follow-up is primed for success.
Validated CU tools have been translated into multiple languages and studied in diverse populations, which supports the creation of a platform with a culturally and linguistically appropriate design and function.
There are tools that have been translated into Chinese and studied in Chinese populations. There are also tools that we would need to translate and do field testing in our population to make sure they are understandable and reliable. We have outlined these tools below. We would ask for community partner input (patients, allergists, primary care physicians) to determine which tools would be preferred for use in the app. Lulu Tsao, who is fluent in English and Chinese, will conduct semi-structured interviews with Chinese and Chinese-American patients to gauge their interest in an app, how they would want to use an app (symptoms, messaging, photos), and whether they would want recommendations from an allergist via an app.
- The UAS has been used in research studies in both mainland China and Taiwan. It was used in a cross-sectional survey of about 3000 patients in tertiary hospitals in different provinces.
- The DLQI has also been used for Chinese patients and an official Chinese (traditional and simplified) version is available online. This version was studied among 148 patients with CU in Taiwan and found to have high reliability.
- The Urticaria Control Test (UCT) is available in 30 languages and consists of only 4 questions, although the translated versions are not readily available.
- The CU-Q20L has not been translated or validated in Chinese populations, and translation and field testing with our population is needed to make sure it is understandable and reliable.
If an initial pilot in a Chinese-speaking population is successful, our plan is to also expand the platform to include Spanish-speaking patients. At that point, similar review of existing symptom and quality of life scoring tools and discussions with the appropriate community partners will be undertaken to determine which tools are most suitable for this patient population. In terms of already validated tools, the UAS and UAS7 were validated by researchers in Spain in a multicenter study of 166 patients and found to have good internal consistency, reliability, and sensitivity to change.
Ideally, the Eureka Research Platform would be used for the following aspects of the online platform. Features within each section are listed in order of highest to lowest priority.A. Electronic consent
- Study enrollment
- Medical release form: On enrollment, patients will specify which providers they would like to keep informed about their hive treatment and sign a medical release form to grant these providers HIPAA-compliant access to a report of their work-up and treatment plans.
- Omalizumab (advanced CU treatment) consent form: This capability will prevent delays in care that occur when medication orders cannot be processed because patients cannot come to clinic to sign consent.
B. Symptom tracking: As there are pros and cons to each of the tools described, we will work with community partners to determine which tools will be used in the platform.
- UAS / UAS-7: Allow patients to track their symptoms daily, or even multiple times a day, a request made by users of current apps.
- Record hive triggers: Allow patients to track and identify non-allergic and physical triggers for urticaria.
- PHQ-2 / PHQ-9: Use depression screening tools to identify patients who could benefit from timely referral to psychology or psychiatry as appropriate. Up to 50% of patients with CU are affected by depression but many of them do not seek treatment. If possible, collaboration with existing online therapy apps would be ideal.
- Quality of life reports: Incorporate CU-specific quality of life surveys (CU-Q2OL, DLQI) to assess CU wellness over time.
- Smartphone-based reminders: Patients can opt in for reminders to submit their daily scores and response to medications.
C. Store patient-generated health data
- Data storage (photos of hives, photos of medication, pre-populated symptom lists, and speech-text interfaces) that reduces the need for real-time translation would improve patient-provider engagement and facilitate shared decision-making. It would clarify what treatments non-English-speaking patients are using.
- Having a report of patient-generated health data that can be recorded by patients from diverse cultural and language backgrounds would allow patients and providers to better engage in meaningful shared decision-making.
D. Facilitate communication between patients and allergists
- It would be ideal if allergists could remotely access the patient-reported data for their patients. This would allow patients to share their symptom and quality of life scores and update their allergist about what prescription, over-the-counter, and herbal medications they are taking. The allergist would take this data and recommend medication changes if necessary. A platform that could interface with Epic would streamline provider workflow, but it would be understandable if that feature is not a possibility.
- If allergists can’t access the patient-reported data unless the patient comes to clinic, the platform would still be helpful in terms of decreasing cultural and language barriers between the patient and the provider, because the app would store patient-generated health data (symptom-tracking data, medication use data, and possible triggers for the hives) that could be reviewed during the appointment. However, in this case the app would not help in terms of eliminating distance and time barriers for patients.
E. Facilitate data transfer between patients, allergists, and PCP providers
- The platform would generate a report of patients' work-up and treatment plans that can be faxed to their primary care providers for the allergy office.
- The platform would also serve as an updated physical “medical file” that the patient could show any provider during in-person clinic visits. As such, especially if the platform could interface with Epic, this study would also be an exploration into whether smartphone-based health data owned and carried by patients is indeed an effective way to store health data so that it is accessible by patients and their providers.
F. Linkage to EHR
- We could connect treatment response in our cohort to clinical data, such as autoantibody levels, to better understand the biology of CU.
Partnership with community advisors will be integral to the success of our proposed engagement platform for CU patients. As one of the highlights of our proposed platform is that it will be accessible by diverse populations, it is imperative that we work with community partners to gauge their interest in our project and to ask for their input regarding the platform.
- Primary care physicians at UCSF
- Primary care physicians in the San Francisco Bay Area
- Primary care physicians who work at clinics focused on care for patients of Chinese backgrounds (Chinatown Public Health Center in SFHN, Chinese Hospital, etc.)
- Chinese traditional medicine and acupuncture clinics in San Francisco
- Local organizations such as Asian Alliance for Health, Asian Health Institute, Chinese Community Health Resource Center, and Southeast Asia Research Institute.
- Patients with chronic hives
- Spanish-speaking, if initial pilot with Chinese-speaking population is successful
- What can we do to make this engagement platform useful for your patients and for you?
- Do you think that it will be helpful to broaden recruitment to chronic hive patients who are not referred to allergy practices?
- What outcome measures would you be interested in knowing?
We would like to ask traditional medicine and acupuncture clinics about their current practices and how they might be integrated into our platform. Patients are increasingly interested in the role of complementary and alternative medicine (CAM) in treating atopic conditions such as hives. It is also important to improve our understanding of how patients, particularly Asian patients, perceive and use CAM.
- What can we do to make this engagement platform useful for you?
- Which symptom-tracking and quality-of-life tools would you want in the platform?
- We would also discuss any specific culturally important aspects of care that patients would like integrated into an engagement platform.
- Is there a clinically relevant difference at week 8 in the Urticaria Activity Score (UAS7) compared to baseline?
Secondary research aims:
- Investigate if there are clinically relevant differences between baseline and week 8 for other measurement outcomes requested by community partners, such as quality of life
- Obtain Kaplan-Meier estimates of the distribution of time to first minimum important difference (MID) response in UAS7 (i.e. time to a reduction from baseline in ≥ 10 points) to estimate the median time to MID.
- Compare the two language cohorts to identify differences in frequency of using the platform, frequency of messaging, or effect on UAS outcome that are potentially related to language accessibility
We expect to enroll 17 patients to detect a mean change in UAS7 at 8 weeks from baseline of 11 points (standard deviation 9 points) with 90% statistical power. This is based on a paired t-test, alpha of 0.05. A total of 34 patients will be recruited, 17 in each subgroup (English-speaking and Chinese-speaking patients). We would be able to enroll this number of patients within three months given the volume of hive patients we see. The minimal clinically important difference for the UAS7 is 10-11 points, and the standard deviation of the mean UAS7 at baseline in CU studies is 9 points. If we are able to combine the two cohorts, Asian speaking and English speaking, and/or enroll 20 people in each subgroup, we will explore the trajectory over time using a linear mixed-effects regression model.
As stated, if the initial pilot study is successful and community partners show interest, we will obtain qualitative feedback from current Spanish-speaking Latin@ chronic hive patients to tailor the platform design and function to the Latin@ population and perform a feasibility pilot study with Spanish-speaking patients.
Next steps: Randomized control trial (RCT)
If the feasibility studies are successful in showing a clinically relevant difference at week 8 in the Urticaria Activity Score (UAS7) compared to baseline, our long-term goal is to conduct a randomized controlled clinical trial (RCT) with a non-intervention group. The intervention arm would consist of patients treated by allergy providers who offer the platform, and the control arm would consist of patients treated by allergy providers who do not offer the platform and track patient symptom scores using paper forms and analog patient diaries. The clinic scheduler will randomize patients referred for hives to the intervention or control arm. Prior to starting the RCT, we will work with a biostatistician to finalize the study design and statistical analyses pending community partner input and outcomes of initial feasibility studies.
Next steps: RCT Primary Aim
- Is there a clinically relevant difference at week 8 in the UAS7 between the intervention and the control group?
Next steps: RCT secondary research questions:
- Does an online platform allow patients to engage sooner with an allergist after initial referral to Allergy is placed?
- Compared to routine care (in-person visits), does an online platform for self-directed symptom tracking and clinician engagement achieve symptom control more quickly?
- Does achieving symptom control in the first 12 weeks after symptom onset result in increased likelihood of remission (complete control of symptoms without treatment) at 6 months, 1 year, 2 years, and 3 years after symptom onset?
- Are improvements in symptom control associated with improvements in the Chronic Urticaria Quality of Life Questionnaire (CU-Q2OL)?
- Saini SS, Kaplan AP. Chronic Spontaneous Urticaria: The Devil's Itch. J Allergy Clin Immunol Pract. 2018 Jul - Aug;6(4):1097-1106. doi: 10.1016/j.jaip.2018.04.013.
- Deza G, Ricketti PA, Giménez-Arnau AM, Casale TB. Emerging Biomarkers and Therapeutic Pipelines for Chronic Spontaneous Urticaria. J Allergy Clin Immunol Pract. 2018 Jul - Aug;6(4):1108-1117.
- Zuberbier T, Bernstein JA. A Comparison of the United States and International Perspective on Chronic Urticaria Guidelines. J Allergy Clin Immunol Pract. 2018 Jul - Aug;6(4):1144-1151. Epub 2018 May 18.
- Hawro T, Ohanyan T, Schoepke N, Metz M, Peveling-Oberhag A, Staubach P, Maurer M, Weller K. The Urticaria Activity Score-Validity, Reliability, and Responsiveness. J Allergy Clin Immunol Pract. 2018 Jul - Aug;6(4):1185-1190.e1. Epub 2017 Nov 8.
- Greenberger PA. Chronic Urticaria: new management options. World Allergy Organ J. 2014 Nov 5;7(1):31.
- Bernstein JA et. al. The diagnosis and management of acute and chronic urticaria: 2014 update. J Allergy Clin Immunol. 2014 May;133(5):1270-7.
- Vietri J et. al. Effect of chronic urticaria on US patients: analysis of the National Health and Wellness Survey.Ann Allergy Asthma Immunol. 2015 Oct;115(4):306-11.
- Zhong H, Song Z, Chen W, Li H, He L, Gao T, Fang H, Guo Z, Xv J, Yu B, Gao X, Xie H, Gu H, Luo D, Chen X, Lei T, Gu J, Cheng B, Duan Y, Xv A, Zhu X, Hao F. Chronic urticaria in Chinese population: a hospital-based multicenter epidemiological study. Allergy 2014; 69: 359–364.
- Liu JB, Yao MZ, Si AL, Xiong LK, Zhou H. Life quality of Chinese patients with chronic urticaria as assessed by the dermatology life quality index. J Eur Acad Dermatol Venereol. 2012 Oct;26(10):1252-7. doi: 10.1111/j.1468-3083.2011.04277.x. Epub 2011 Sep 29.
- Balañá M, Valero A, Giménez Arnau A, Ferrer M, Jauregui I, Ballesteros C; study group of EVALUAS. Validation of The Spanish Version of The Urticaria Activity Score (Uas) and Its Use Over One Week (Uas7).Value Health. 2015 Nov;18(7):A426. doi: 10.1016/j.jval.2015.09.584. Epub 2015 Oct 20. *note this was for Novartis.
- Chronic Hives by the American Academy of Dermatology. https://www.aad.org/members/aad-apps/chronic-urticaria-for-public.
- CIU Tracker. https://itunes.apple.com/us/app/ciu-tracker/id977990786?mt=8
- Target My Hives. http://myhives.com/en/
Commenting is closed.