Practical application of good participatory practices for trials of emerging pathogens: Developing materials for use in ACTIV-3, -3b, and ACTIV-associated COVID-19 trials

Abstract

The emergence of the COVID-19 pandemic required an immediate global clinical research response. The ACTIV (Accelerating COVID-19 Therapeutic Interventions and Vaccines)-3 trials and the ACTIV-associated Outpatient Treatment with Anti-Coronavirus Immunoglobulin trial used Good Participatory Practices (GPP) to develop materials for study implementation from a global network perspective. GPP guidelines offer a framework for engaging stakeholders throughout the research process. This paper provides an overview of the materials developed and their applicability in various settings, reports results from a survey of study site personnel on the materials' usefulness, summarizes important lessons learned, and serves as a reference for networks eager to apply GPP. Survey results showed that flipbooks and overview videos were highly ranked. Stakeholder input was valuable in developing easily understandable participant-facing materials with culturally appropriate images. Materials should be available to submit with the initial protocol submissions to ethics committees, and in formats that accommodate a wide range of institutional resources, policies, and infection-control practices. This article emphasizes the importance of GPP, including stakeholder consultation, in developing materials that support clinical research and address language, cultural, and sociopolitical barriers during a pandemic. The findings will be used to optimize efforts and resource allocation for new and ongoing studies.

Keywords: COVID-19 trials; Good Participatory Practice; clinical trial implementation; informed consent process; participant-facing materials; recruitment; stakeholder engagement.

Figure 1.

ACTIV -3, -3 substudy, -3b and outpatient treatment with anti-coronavirus immunoglobulin (OTAC) trials infrastructure and communication pathways. The infrastructure established for developing and implementing ACTIV (Accelerating COVID-19 Therapeutic Interventions and Vaccines)-3, -3 substudy, -3b, and ACTIV-associated COVID-19 clinical trials consisted of a central International Network for Strategic Initiatives in Global HIV Trials (INSIGHT) Statistical and Data Management Center (SDMC) at the University of Minnesota that oversaw various international coordinating centers (ICCs) that managed site coordinating centers (SCCs) and sites in various countries. Sites listed in the figure are those which enrolled in at least one of the studies through July 31, 2022. Abbreviations: ALIGNE = Acute Lung Injury Group New England; CTSN = Cardiothoracic Surgical Trials Network; DCR = Division of Clinical Research; LaRed = Mexican Emerging Infectious Disease Clinical Research Network; NIH/NIAID = National Institutes of Health/National Institute of Allergy and Infectious Diseases; PETAL = Prevention and Early Treatment of Acute Lung Injury; SCC = Site Coordinating Centers; US = United States of America; WDC = Washington, District of Columbia.

Figure 2.

Framework for prioritization of potential study materials and activities. Matrix used to prioritize activities and materials for study implementation based on anticipated impact and predicted difficulty, time, and cost for development, approval, and production.

Figure 3.

Process for development and production of participant-facing materials. The process for developing and producing material included a continuous interaction with stakeholders from conceptualization, development, review, and approval through translation. Final materials were posted on the password-protected International Network for Strategic Initiatives in Global HIV Trials (INSIGHT) member website where sites could download them at any time. Sites could choose to download the items to a computer or mobile device, print them locally, and/or request that they be printed and shipped to them. The study overview videos and flipbooks were also posted for public access on the CombatCOVID study-specific web pages and, subsequently, on the National Institute of Allergy and Infectious Diseases (NIAID) study-specific web pages. Abbreviations: EC = ethics committee; GPP = Good Participatory Practices.

Figure 4.

Average usefulness of the materials provided for ACTIV-3, -3 substudy, -3b, and OTAC, and estimates of resources used in producing them. This chart presents a rough estimate of the relative costs, difficulty, and time required to produce each type of material, including securing United States central institutional review board approval, as appropriate. Survey respondents were requested to rate the usefulness of each type of material for all studies in which they used them, or indicate if they had not used the material in particular studies. Usefulness of each material for each study was rated on a 5-point scale (not useful, minimally useful, somewhat useful, very useful, and extremely useful). The chart also shows the combined average ratings of materials for all four studies provided by the international coordinating centers (ICCs), site coordinating centers (SCCs), or sites that used the materials. Abbreviations: ACTIV = Accelerating COVID-19 Therapeutic Interventions and Vaccines; COVID = coronavirus disease; FAQ = frequently asked questions; hIVIG = (anti-coronavirus) hyperimmune intravenous immunoglobulin; IRB = Institutional Review Board; L-R = Left to Right; OTAC = Outpatient Treatment with Anti-coronavirus Immunoglobulin.