2023 HSR&D/QUERI National Conference

4082 — Navigating COVID-19 and Related Challenges to Completing Clinical Research: Lessons Learned from the PATRIOT and STEP-UP Randomized Prevention Trials

Lead/Presenter: Priscilla Salovaara,  VA New York Harbor Healthcare System
All Authors: Salovaara PK (Columbia University, VA New York Harbor Healthcare System), Li, C (New York University, VA New York Harbor Healthcare System) Nicholson, A (New York University Grossman School of Medicine, VA New York Harbor Healthcare System) Lipsitz, S (Brigham and Women's Hospital, Harvard Medical School) Natarajan, S (New York University Grossman School of Medicine, VA New York Harbor Healthcare System)

Achieving high follow-up is an important quality metric for randomized clinical trials (RCTs). When clinical research was halted due to COVID-19, we were in the final data collection phase for STEP UP, a secondary prevention trial focused on preventing recurrent diabetic foot ulcers, and PATRIOT, a primary prevention trial targeted at preventing incident foot lesions among high-risk Veterans with diabetes. While maintaining study integrity, we implemented remote data collection for STEP UP and modified in-person assessments for PATRIOT. The effectiveness of these new strategies and their impact on successful study completion were formally evaluated.

A quasi-experimental pre-post design compared approaches for follow-up during COVID-19 to approaches pre-COVID-19. Study participants were outpatients at two VA Medical Centers. Research resumed in February 2021 for STEP UP (n = 241), and in April 2021 for PATRIOT (n = 406). To complete data collection, we shortened visits, focused on primary and secondary outcomes, and conducted virtual visits when appropriate. For STEP UP, we created a twenty-minute telephone assessment process. Since PATRIOT required plantar photographs to assess foot lesions, we conducted short face-to-face visits. We assessed proportion completing visit, visit completion/100 person-months and compared COVID-19 rates to pre-COVID-19 using unadjusted risk ratios (RR), incidence rate ratios (IRR), and visit follow-up curves.

In both studies, active participants during COVID-19 were younger than those whose follow-up concluded pre-COVID-19 (PATRIOT: 72.4 vs. 67.8 years, p = 0.0044; STEP UP: 71.6 vs. 67.7, p = 0.0025). Further, in STEP UP, there was a higher proportion of smokers (34.1% vs. 17.9%, p = 0.0065). We completed 91 STEP-UP visits pre-COVID- 19 [37.76% (31.62%, 44.21%)] and 63 visits during COVID-19 [78.75% (68.17%, 87.11%)]. This was over 1309 person-months pre-COVID-19, and over 208.8 person-months during COVID-19; the visit completion rate/100 person-months were: pre-COVID-19: 7.0 (CI 5.6, 8.5), COVID-19: 29.7 (CI 22.8, 38.1); RR: 2.1 (CI 1.7, 2.5) p < < 0.001; and IRR 4.3 (CI 3.1, 5.9) p < < 0.0001. We completed 316 PATRIOT visits pre-COVID-19 [77.83% (73.47%, 81.78%)] and 27 assessments during COVID-19 [84.38% (67.21%, 94.72%)]. This was over 1192.7 person-months pre-COVID-19 and 39.3 person-months during COVID-19. The visit completion rate/100 person-months in PATRIOT was: pre-COVID-19: 2.7 (CI 2.4, 3.0); COVID-19: 6.9 (CI 4.5, 10); RR: 1.1 (CI 0.9, 1.3) p = 0.56; IRR: 2.6 (CI 1.8, 3.8) p < 0.0001. For both studies, the follow-up curves began separating at < 2 months (Log-Rank test p-values: STEP UP 0.0002; PATRIOT < 0.0001).

We achieved higher completion rates during COVID-19 than pre-COVID-19 by modifying visits and focusing on primary and secondary outcomes. These strategies prevent excessive missing data, support more valid conclusions, and improve efficiency. They may provide important alternative strategies to achieving higher follow-up in RCTs.

Shortened assessments, patient-centered scheduling, and flexible assessment modalities enabled the collection of valid data for the final analyses of STEP UP and PATRIOT, despite pandemic restrictions. This reduces the problem of excessive missing data and allows for more valid conclusions to be drawn in these RCTs. These methods might be effective for clinical trials in the uncertain COVID-19 landscape, and, broadly, for improving clinical trial efficiency and completion rates.