In a swift response to the COVID-19 pandemic, many sponsors are rapidly working toward new vaccine trials to fill the urgent need for a safe and effective treatment. The first US clinical trial1 to evaluate a treatment for COVID-19 is underway by the National Institute of Allergy and Infectious Diseases (NIAID), but results are still many months away. The acute time pressures that vaccine trials typically have are now in hyper speed.
Traditionally in vaccine trials, patient reported data are collected via paper based assessments and symptom diary cards. This approach, however, is often more costly, error-prone, and cumbersome to both patients and sites, especially considering that global vaccine programs are very large with diverse patient populations. Given the need for expedited results with minimal error, sponsors may want to consider an electronic data capture solution that will provide high quality, consistent data and allow for a quick review of patient data in real-time.
Using eCOA to support data collection in vaccine studies
An important component of vaccine trial preparation is planning for at home patient reported data capture in healthy subjects. Many sponsors presume that providing patients with paper diaries will help save time in study start-up (compared to using electronic methods). However, this problem is analogous to a ship rapidly approaching an iceberg, where the bulk of the inevitable damage, and in this case the extensive time requirements, are hidden from plain sight.
Vaccine trials collect an enormous amount of data. For example, a two-dose vaccine study of 10,000 patients can generate 6.6 million data points (Figure 1). With paper diaries, site staff would be required to manually review and enter each of these data points into the trial database, which amounts to a very time-intensive, costly, and error prone process as the study progresses, further putting study timelines at risk.
Collecting electronic clinical outcome assessments (eCOA) eliminates the need for time consuming data transcription and validation steps, which can help to accelerate timelines to ensure on-time database lock. An electronic patient diary (eDiary) can incorporate various safeguards in order to collect more accurate, attributable data sets. The software can be set to specific time windows for completion, incorporate prompts and alarm messages to serve as daily reminders, and provide time-stamps for each data point to ensure clean audit trails for sponsors and regulators.
Additionally, the EMA2 states that electronic data capture methods may offer more convenience to patients, which is an important factor to consider in the context of a patient’s daily life and voluntary involvement in a vaccine trial. User-friendly electronic diary designs (e.g. one question per screen, simple prompts) have been shown to improve patient compliance3,4 (Figure 2) minimize missing data, and alleviate patient burden.
Considerations for BYOD
There is growing interest for more patient-centric trial models in which the patient has the freedom to use their own device to complete the eDiary. This usually results in a mixed-device trial, a common approach in vaccine trials, where either the diary is pre-loaded onto provisioned devices by the sponsor or the patient downloads the application onto their own device, also known as bring-your-own-device, or BYOD.
Recently, the FDA published a discussion document after the patient focused drug development workshop5 that acknowledges the increasing interest in BYOD. However, the FDA still recommends using a single platform throughout a clinical trial to reduce noise in the data. If a sponsor does want to proceed with BYOD, it is important that a detailed plan is provided to the FDA for review and comment to ensure that the diary will function as intended across devices.
Configurable vaccine platform
Patient reported diaries often capture reactogenicity (i.e. expected adverse reactions) after vaccination, which may contribute to primary endpoint data in global vaccine trials. These trials also require several languages and localized questions to accommodate diverse patient groups. Traditional methods of creating novel diaries on paper take a great deal of time to test and validate, however, by using pre-validated electronic questions tailored to capture expected local and systemic signs and symptoms, the sponsor can customize a diary that is appropriate for their population, study schedule, and language requirements. This type of pre-validated platform can serve as a valuable resource to help expedite timelines and reduce start-up costs, but still ensure that data integrity and regulatory requirements are kept intact.
Actions from FDA and WIRB to expedite IND review
The FDA is currently working closely with sponsors to help speed up development of COVID-19 treatments6. They have started expediting the usual 30 day waiting period for initial safety review alongside pre-investigational new drug (IND) discussions so that trials may begin as soon as possible.
Additionally, the WIRB-Copernicus IRB has announced a new program that will prioritize review of COVID-19 protocols conducted under an IND application to expedite the start-up of clinical trials for COVID-19 vaccines and therapies7.
Nadeeka Dias, PhD is a Sr. Clinical Science Advisor at ERT.
- NIH Clinical Trial of Remdesivir to Treat COVID-19 Begins. February 25, 2020. https://www.niaid.nih.gov/news-events/nih-clinical-trial-remdesivir-treat-covid-19-begins
- Reflection Paper on the use of patient reported outcome (PRO) measures in oncology studies (draft). June 2014. https://www.ema.europa.eu/en/documents/scientific-guideline/draft-reflection-paper-use-patient-reported-outcome-pro-measures-oncology-studies_en.pdf
- Bingham, C.O., Gaich, C.L., DeLozier, A.M. et al. (2019) Use of daily electronic patient-reported outcome (PRO) diaries in randomized controlled trials for rheumatoid arthritis: rationale and implementation. Trials 20 (182).
- McKenzie, S., Paty, J. and Grogan, D. et al. (2004). Proving the eDiary dividend. Applied Clinical Trials, 13(6): 54–68.
- Discussion Document for Patient-Focused Drug Development Public Workshop on Guidance 3: Select, Develop or Modify Fit-For-Purpose Clinical Outcome Assessments. October 2018. https://www.fda.gov/media/116277/download
- Coronavirus Disease 2019 (COVID-19). February 25 2020. https://www.fda.gov/emergency-preparedness-and-response/mcm-issues/coronavirus-disease-2019-covid-19
- IRB Announces New Program to Facilitate IRB Review of Research Protocols for COVID-19 (Coronavirus) Vaccines and Therapies. March 6 2020. https://www.pharmavoice.com/newsreleases/wcgs-wirb-copernicus-irb-announces-new-program-facilitate-irb-review-research-protocols-covid-19-coronavirus-vaccines-therapies/