Speaker
Harlan M. Krumholz, MD, SM
Harold H. Hines, Jr. Professor of Medicine
Department of Internal Medicine
Section of Cardiovascular Medicine
Yale University School of Medicine
Director, Yale-New Haven Hospital Center for Outcomes Research and Evaluation
Keywords
Decentralized Trial, Digital Trial, Yale PaxLC Trial, Long COVID
Key Points
- The PaxLC Trial is a decentralized Phase 2, 1:1 randomized double-blind superiority placebo-controlled study on non-hospitalized high symptomatic adult participants with Long Covid to determine the efficacy, safety, and tolerability of 15 days of Nirmatrelvir/Ritonavir compared with a Placebo/Ritonavir.
- This talk describes the PaxLC Trial’s strategies to implement a digital, decentralized, and democratized approaches to multidisciplinary research that address the deficiencies of traditional research studies, which can tend to be hierarchical, siloed, slow, expensive, and inconvenient.
- A key question for the study was how do we put the interest of the participants first and foremost and produce knowledge rapidly? Research can improve by simultaneously leveraging advances in technology and culture. Studies must be convenient, meaningful, respectful, efficient, rapid, and fair.
- The research optimization requires partnership with participants, including involvement in study design and workflow, data collection and analysis, and data and results sharing. Participants should have access to investigators and the results of studies.
- PaxLC brings together many innovations including online screening, digital medical record review, e-consent, home-delivery of medications, local clinical blood draws, home-based biospecimen collection, online diaries and surveys, digital medical record outcomes, and participant-centricity, and return of results. During the presentation, members from across the research team shared how PaxLC implemented all of these innovations through the course of the trial.
Discussion Themes
-What have you experienced on the scalability of the approaches you have taken, such as regulations and IRB? Is this knowledge generalizable to other similar trials? Using the local Yale IRB was an asset. We had to have the right people in the room to initiate communication with collaborators and their IRB representatives. The Yale IRB and Trusted Medical helped facilitate the other states and anything we need to take in account for recruitment. We will have a repository with Trusted Medical for future studies. We had to operate the trial with an institution that would allow zero risk. We had to come up with solutions.
-Can you comment on the decision to make the PROMIS scale the primary outcome? Does it capture most what matters to patients? We spent a lot of time discussing what would be the best primary outcome. Pfizer provided feedback. We wanted to measure a lot of stuff. We were familiar with the PROMIS scale and felt PROMIS would capture whether people were feeling better. We wanted to say if this is working, people’s general health should improve.
–How do you organize recruitment to ensure you have the diversity you want and how do you explain to people you are turning away? It’s a multipronged strategy. Be welcoming and be authentically committed to health equity and be worthy of the trust. One of the main reasons we turn people away is because they are taking a medication that does not work with Paxlovid. A lot of participants have worked with their physician to stop a drug so they can participate.
Tags
#pctGR, @Collaboratory1