Rigorous Clinical Trial Design in Public Health Emergencies Is Essential

Abstract

Randomized clinical trials are the most reliable approaches to evaluating the effects of new treatments and vaccines. During the 2014-2015 West African Ebola epidemic, many argued that such trials were neither ethical nor feasible in an environment of limited health infrastructure and severe disease with a high fatality rate. Consensus among the numerous organizations providing help to the affected areas was never achieved, resulting in fragmented collaboration, delayed study initiation, and ultimately failure to provide definitive evidence on the efficacy of treatments and vaccines. Randomized trials were in fact approved by local ethics boards and initiated, demonstrating that randomized trials, even in such difficult circumstances, are feasible. Improved planning and collaboration among research and humanitarian organizations, and affected communities, in the interepidemic periods are needed to ensure that questions regarding the efficacy of vaccines and treatments can be definitively answered during future public health emergencies.

Addressing challenges for clinical research responses to emerging epidemics and pandemics: a scoping review

“…A cross-cutting theme identified was the need to strengthen collaboration and coordination between organisations involved in outbreak response at all levels [3,7,81]. Effective partnerships between countries and international organisations, such as public health, clinical research organisations, non-governmental organisations (NGOs), pharmaceutical companies and regulatory agencies, were described as instrumental for success [3,14,16,19]. International research collaborations should be tied to capacity building and be genuinely collaborative [22], with local stakeholders engaged from inception [1, 3, 13, 16-19, 22, 26, 29, 31, 32, 36, 38, 40, 44, 50, 51].…”

“…Shaw et al [73] Ethical and social solutions identified (Table 4) The temporal and spatial variation in the risk of infection during outbreaks presents not only statistical hurdles but also an ethical challenge for study designs [75]. Previous research responses have highlighted the many challenges in agreeing on simultaneously ethical, scientifically valid and acceptable study designs [18,36,42,51,59,64,66], addressing socially valuable questions [14,18,64,66]. The exclusion of children and pregnant women was an ethical concern during the Ebola outbreak in LMICs [18,69], compounded by challenges of obtaining complex consent [2, 4, 5, 15, 18, 21, 25, 32, 34, 44-46, 50, 69, 70].…”

“…Ethical issues also arose around equity in access to health care for participants and nonparticipants [44,50,59]. There were calls for international standards for the conduct of emergency research [21,51,60,62], [51], acceptable study designs [14] and simplified consent methods [2,3,6,25,37,46,51,70,74]. Some studies explored waivered consent [2,25,69,70,74] and/or proxy consent [69].…”

Continuing versus suspending angiotensin-converting enzyme inhibitors and angiotensin receptor blockers: Impact on adverse outcomes in hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)--The BRACE CORONA Trial

“…3 In the context of public health emergencies, conducting a randomized clinical trial can be even more challenging. 4 The shortfalls of the contemporary clinical trial system include the increasingly prohibitive costs, local and national regulatory requirements, delays in approval, and unnecessary trial processes. 5 Over the past decade, innovations in trial design have been deployed to facilitate trial conduct.…”

Evidence-Based Practical Guidance for the Antithrombotic Management in Patients With Coronavirus Disease (COVID-19) in 2020

“…Experienced colleagues demonstrated that RCT, even in such difficult circumstances, was not only feasible but the only reliable way that could provide proper guidance, in contrast to the empirical strategies employed during pandemic times. 26 Many different trials evaluating anticoagulants and other strategies for both VTE prophylaxis and treatment are currently ongoing. Reliable data will be available soon, but until then, physicians should do what has been proven to be efficient and safe and in case of uncertainty randomize patients into ongoing clinical trials.…”