Christopher J Lindsell, Matthew Shotwell, Kevin J Anstrom, Scott Berry, Erica Brittain, Frank E Harrell, Nancy Geller, Birgit Grund, Michael D Hughes, Prasanna Jagannathan, Eric Leifer, Carlee B Moser, Karen L Price, Michael Proschan, Thomas Stewart, Sonia Thomas, Giota Touloumi, Lisa LaVange
{"title":"The statistical design and analysis of pandemic platform trials: Implications for the future.","authors":"Christopher J Lindsell, Matthew Shotwell, Kevin J Anstrom, Scott Berry, Erica Brittain, Frank E Harrell, Nancy Geller, Birgit Grund, Michael D Hughes, Prasanna Jagannathan, Eric Leifer, Carlee B Moser, Karen L Price, Michael Proschan, Thomas Stewart, Sonia Thomas, Giota Touloumi, Lisa LaVange","doi":"10.1017/cts.2024.514","DOIUrl":"10.1017/cts.2024.514","url":null,"abstract":"<p><p>The Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) Cross-Trial Statistics Group gathered lessons learned from statisticians responsible for the design and analysis of the 11 ACTIV therapeutic master protocols to inform contemporary trial design as well as preparation for a future pandemic. The ACTIV master protocols were designed to rapidly assess what treatments might save lives, keep people out of the hospital, and help them feel better faster. Study teams initially worked without knowledge of the natural history of disease and thus without key information for design decisions. Moreover, the science of platform trial design was in its infancy. Here, we discuss the statistical design choices made and the adaptations forced by the changing pandemic context. Lessons around critical aspects of trial design are summarized, and recommendations are made for the organization of master protocols in the future.</p>","PeriodicalId":15529,"journal":{"name":"Journal of Clinical and Translational Science","volume":"8 1","pages":"e155"},"PeriodicalIF":2.1,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11557281/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142636100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stacey J Adam, Sarah E Dunsmore, Lisa H Merck, Sarah W Read, Yves Rosenberg
{"title":"The future is now: Using the lessons learned from the ACTIV COVID-19 therapeutics trials to create an inclusive and efficient clinical trials enterprise.","authors":"Stacey J Adam, Sarah E Dunsmore, Lisa H Merck, Sarah W Read, Yves Rosenberg","doi":"10.1017/cts.2024.622","DOIUrl":"10.1017/cts.2024.622","url":null,"abstract":"","PeriodicalId":15529,"journal":{"name":"Journal of Clinical and Translational Science","volume":"8 1","pages":"e148"},"PeriodicalIF":2.1,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11523011/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
David A Wohl, Stacey J Adam, Kevin W Gibbs, Ari L Moskowitz, Thomas L Ortel, Upinder Singh, Nikolaus Jilg, Teresa H Evering, William A Fischer, Babafemi O Taiwo, Eric S Daar, Christopher J Lindsell, Susanna Naggie, Russell L Rothman, Sarah E Dunsmore, M Patricia McAdams, Julia Vail, Dushyantha Jayaweera
{"title":"Engaging communities in therapeutics clinical research during pandemics: Experiences and lessons from the ACTIV COVID-19 therapeutics research initiative.","authors":"David A Wohl, Stacey J Adam, Kevin W Gibbs, Ari L Moskowitz, Thomas L Ortel, Upinder Singh, Nikolaus Jilg, Teresa H Evering, William A Fischer, Babafemi O Taiwo, Eric S Daar, Christopher J Lindsell, Susanna Naggie, Russell L Rothman, Sarah E Dunsmore, M Patricia McAdams, Julia Vail, Dushyantha Jayaweera","doi":"10.1017/cts.2024.561","DOIUrl":"10.1017/cts.2024.561","url":null,"abstract":"<p><p>This manuscript addresses a critical topic: navigating complexities of conducting clinical trials during a pandemic. Central to this discussion is engaging communities to ensure diverse participation. The manuscript elucidates deliberate strategies employed to recruit minority communities with poor social drivers of health for participation in COVID-19 trials. The paper adopts a descriptive approach, eschewing analysis of data-driven efficacy of these efforts, and instead provides a comprehensive account of strategies utilized. The Accelerate COVID-19 Treatment Interventions and Vaccines (ACTIV) public-private partnership launched early in the COVID-19 pandemic to develop clinical trials to advance SARS-CoV-2 treatments. In this paper, ACTIV investigators share challenges in conducting research during an evolving pandemic and approaches selected to engage communities when traditional strategies were infeasible. Lessons from this experience include importance of community representatives' involvement early in study design and implementation and integration of well-developed public outreach and communication strategies with trial launch. Centralization and coordination of outreach will allow for efficient use of resources and the sharing of best practices. Insights gleaned from the ACTIV program, as outlined in this paper, shed light on effective strategies for involving communities in treatment trials amidst rapidly evolving public health emergencies. This underscores critical importance of community engagement initiatives well in advance of the pandemic.</p>","PeriodicalId":15529,"journal":{"name":"Journal of Clinical and Translational Science","volume":"8 1","pages":"e156"},"PeriodicalIF":2.1,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11557280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Maryam Keshtkar-Jahromi, Kevin J Anstrom, Christina Barkauskas, Samuel M Brown, Eric S Daar, William Fischer, Kevin W Gibbs, Elizabeth S Higgs, Michael D Hughes, Prasanna Jagannathan, Lisa LaVange, Christopher J Lindsell, Seema U Nayak, Roger Paredes, Mahesh Parmar, Ithan D Peltan, Michael Proschan, Matthew S Shotwell, David M Vock, Tammy Yokum, Stacey J Adam
{"title":"ACTIV trials: Lessons learned in trial design in the setting of an emergent pandemic.","authors":"Maryam Keshtkar-Jahromi, Kevin J Anstrom, Christina Barkauskas, Samuel M Brown, Eric S Daar, William Fischer, Kevin W Gibbs, Elizabeth S Higgs, Michael D Hughes, Prasanna Jagannathan, Lisa LaVange, Christopher J Lindsell, Seema U Nayak, Roger Paredes, Mahesh Parmar, Ithan D Peltan, Michael Proschan, Matthew S Shotwell, David M Vock, Tammy Yokum, Stacey J Adam","doi":"10.1017/cts.2024.1","DOIUrl":"10.1017/cts.2024.1","url":null,"abstract":"<p><p>Accelerating COVID-19 Treatment Interventions and Vaccines (ACTIV) was initiated by the US government to rapidly develop and test vaccines and therapeutics against COVID-19 in 2020. The ACTIV Therapeutics-Clinical Working Group selected ACTIV trial teams and clinical networks to expeditiously develop and launch master protocols based on therapeutic targets and patient populations. The suite of clinical trials was designed to collectively inform therapeutic care for COVID-19 outpatient, inpatient, and intensive care populations globally. In this report, we highlight challenges, strategies, and solutions around clinical protocol development and regulatory approval to document our experience and propose plans for future similar healthcare emergencies.</p>","PeriodicalId":15529,"journal":{"name":"Journal of Clinical and Translational Science","volume":"8 1","pages":"e151"},"PeriodicalIF":2.1,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11523015/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142550067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stacey J Adam, Timothy G Buchman, Judith S Currier, Ruxandra Draghia-Akli, Josh P Fessel, Elizabeth S Higgs, Eric A Hughes, Lisa LaVange, Joseph P Menetski, Sarah W Read, Yves Rosenberg, Randall Tressler
{"title":"Preparing better: Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) therapeutics trials lessons learned: A call to the future.","authors":"Stacey J Adam, Timothy G Buchman, Judith S Currier, Ruxandra Draghia-Akli, Josh P Fessel, Elizabeth S Higgs, Eric A Hughes, Lisa LaVange, Joseph P Menetski, Sarah W Read, Yves Rosenberg, Randall Tressler","doi":"10.1017/cts.2024.178","DOIUrl":"10.1017/cts.2024.178","url":null,"abstract":"<p><p>The Accelerating COVID-19 Therapeutic Interventions and Vaccines Therapeutic-Clinical Working Group members gathered critical recommendations in follow-up to lessons learned manuscripts released earlier in the COVID-19 pandemic. Lessons around agent prioritization, preclinical therapeutics testing, master protocol design and implementation, drug manufacturing and supply, data sharing, and public-private partnership value are shared to inform responses to future pandemics.</p>","PeriodicalId":15529,"journal":{"name":"Journal of Clinical and Translational Science","volume":"8 1","pages":"e150"},"PeriodicalIF":2.1,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11523022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jane A O'Halloran, Jeremy R Beitler, Lucy K Chung, Mamta K Jain, Akram Khan, Lisa H Merck, Ahmad Mourad, Minn A Oh, Shweta Sharma, Tammy Yokum, Seema U Nayak
{"title":"Lessons learned from the conduct of inpatient clinical trials in a pandemic.","authors":"Jane A O'Halloran, Jeremy R Beitler, Lucy K Chung, Mamta K Jain, Akram Khan, Lisa H Merck, Ahmad Mourad, Minn A Oh, Shweta Sharma, Tammy Yokum, Seema U Nayak","doi":"10.1017/cts.2024.483","DOIUrl":"10.1017/cts.2024.483","url":null,"abstract":"<p><strong>Background: </strong>The COVID-19 pandemic amplified known challenges associated with the conduct of inpatient clinical trials, while also introducing new ones that needed to be addressed.</p><p><strong>Methods: </strong>Stakeholders based in the United States who participated in the conduct of inpatient therapeutic trials for the treatment of COVID-19 as part of the Accelerating COVID-19 Therapeutic Interventions and Vaccines program identified challenges experienced in the conduct of these trials through a series of meeting to discuss and identify common themes. In addition, innovations developed to address these challenges and other potential solutions that may be utilized in future pandemics were highlighted.</p><p><strong>Results: </strong>Six thematic challenges including infection control considerations, the interplay between provision of clinical care and research, competing clinical trials, arduous consenting procedures, onerous procedural requirements, and participant recruitment including achieving representation of diverse populations were identified and are discussed here.</p><p><strong>Conclusions: </strong>Consideration of the lessons learned and recommendation outlined here may allow for more efficient conduct of inpatient clinical trials in future pandemics.</p>","PeriodicalId":15529,"journal":{"name":"Journal of Clinical and Translational Science","volume":"8 1","pages":"e154"},"PeriodicalIF":2.1,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11557273/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Minn A Oh, Judith Currier, Akram Khan, Eleftherios Mylonakis, Matthew Newell, Rachel Bender Ignacio, Nick Jilg, Basmah Safdar, Lisa H Merck, Davey M Smith
{"title":"Lessons learned from COVID-19 to overcome challenges in conducting outpatient clinical trials to find safe and effective therapeutics for the next infectious pandemic.","authors":"Minn A Oh, Judith Currier, Akram Khan, Eleftherios Mylonakis, Matthew Newell, Rachel Bender Ignacio, Nick Jilg, Basmah Safdar, Lisa H Merck, Davey M Smith","doi":"10.1017/cts.2024.607","DOIUrl":"10.1017/cts.2024.607","url":null,"abstract":"","PeriodicalId":15529,"journal":{"name":"Journal of Clinical and Translational Science","volume":"8 1","pages":"e153"},"PeriodicalIF":2.1,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11557272/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Maryam Keshtkar-Jahromi, Stacey J Adam, Indira Brar, Lucy K Chung, Judith S Currier, Eric S Daar, Victoria J Davey, Eileen T Denning, Annetine C Gelijns, Elizabeth S Higgs, Prasanna Jagannathan, Arzhang Cyrus Javan, Tomas O Jensen, Nikolaus Jilg, Ioannis Kalomenidis, Peter Kim, Seema U Nayak, Matthew Newell, Babafemi O Taiwo, Tammy Yokum, Yvette Delph
{"title":"ACTIV trials: cross-trial lessons learned for master protocol implementation.","authors":"Maryam Keshtkar-Jahromi, Stacey J Adam, Indira Brar, Lucy K Chung, Judith S Currier, Eric S Daar, Victoria J Davey, Eileen T Denning, Annetine C Gelijns, Elizabeth S Higgs, Prasanna Jagannathan, Arzhang Cyrus Javan, Tomas O Jensen, Nikolaus Jilg, Ioannis Kalomenidis, Peter Kim, Seema U Nayak, Matthew Newell, Babafemi O Taiwo, Tammy Yokum, Yvette Delph","doi":"10.1017/cts.2024.507","DOIUrl":"10.1017/cts.2024.507","url":null,"abstract":"<p><p>The United States Government (USG) public-private partnership \"Accelerating COVID-19 Treatment Interventions and Vaccines\" (ACTIV) was launched to identify safe, effective therapeutics to treat patients with Coronavirus Disease 2019 (COVID-19) and prevent hospitalization, progression of disease, and death. Eleven original master protocols were developed by ACTIV, and thirty-seven therapeutic agents entered evaluation for treatment benefit. Challenges encountered during trial implementation led to innovations enabling initiation and enrollment of over 26,000 participants in the trials. While only two ACTIV trials continue to enroll, the recommendations here reflect information from all the trials as of May 2023. We review clinical trial implementation challenges and corresponding lessons learned to inform future therapeutic clinical trials implemented in response to a public health emergency and the conduct of complex clinical trials during \"peacetime,\" as well.</p>","PeriodicalId":15529,"journal":{"name":"Journal of Clinical and Translational Science","volume":"8 1","pages":"e152"},"PeriodicalIF":2.1,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11557279/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ruxandra Draghia-Akli, Sarah W Read, Eric A Hughes
{"title":"Overview of ACTIV trial-specific lessons learned.","authors":"Ruxandra Draghia-Akli, Sarah W Read, Eric A Hughes","doi":"10.1017/cts.2023.698","DOIUrl":"10.1017/cts.2023.698","url":null,"abstract":"<p><p>Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) was an extraordinary example of a public-private partnership (PPP) that brought together over thirty organizations and hundreds of individuals to address one of the most pressing global health needs in recent decades. In particular, ACTIV provided a key avenue for testing numerous therapeutics for their potential benefit in treating the SARS-CoV-2 virus or the resulting symptoms of acute COVID-19 infection. Given the speed and scale at which ACTIV designed and implemented master protocols across global networks that it was simultaneously working to create, the PPP can provide valuable lessons for best practices and avoiding pitfalls the next time the world is faced with a global pandemic of a novel pathogen. This report provides a general overview of the ACTIV partnership to set the stage and context for the subsequent articles in this issue that will relay these lessons learned.</p>","PeriodicalId":15529,"journal":{"name":"Journal of Clinical and Translational Science","volume":"8 1","pages":"e149"},"PeriodicalIF":2.1,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11523021/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shannon L Casey, Elizabeth S Burnside, Allan R Brasier
{"title":"Optimizing external advisory committee meetings of Clinical and Translational Science Awards through focused pre-review.","authors":"Shannon L Casey, Elizabeth S Burnside, Allan R Brasier","doi":"10.1017/cts.2024.575","DOIUrl":"10.1017/cts.2024.575","url":null,"abstract":"<p><p>External advisory committees (EACs) are critical peer-review meetings that drive improvement at Clinical and Translational Science Award Program Hubs. Despite their ubiquity, evaluations of EAC optimization and effective implementation remain scarce. We present a two-tiered approach to optimizing EAC meetings through (1) in-depth, topically focused \"pre-review\" meetings comprised of external topic experts and at least one standing \"full-board\" EAC member, followed by (2) a traditional \"full-board\" EAC meeting. This approach allowed pre-review discussion of program-focused topics and specific recommendations, later delivered to the full-board for review and direction. To evaluate this approach, we interviewed 18 people who planned, administered, or attended pre-review and/or full-board meetings, including internal Hub staff, external topic experts, and standing EAC members. Thematic analysis was used to explore planning, implementation, and value of our two-tiered approach <i>versus</i> the traditional single full-board approach. Interviewees preferred the two-tiered approach, noting benefits including additional time to reflect, shared identification of strengths and challenges, and discussion of solutions to share later with the full-board. Those who attended pre-review meetings described building \"<i>transformational</i>,\" rather than <i>\"transactional</i>,\" relationships with invitees through more discussion and inter-hub sharing. That increased sharing invited more exploration, discussion, and planning of next steps toward innovation.</p>","PeriodicalId":15529,"journal":{"name":"Journal of Clinical and Translational Science","volume":"8 1","pages":"e162"},"PeriodicalIF":2.1,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11557274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
