Last week, the World Health Organization (WHO) published data from its SOLIDARITY trial on a preprint server. The SOLIDARITY trial is a global, pragmatic, adaptive, master protocol trial investigating 4 therapies for hospitalized COVID-19 patients, including remdesivir. Disappointing findings for remdesivir in the SOLIDARITY trial elicited a statement from Gilead Sciences, questioning the validity of SOLIDARITY, and emphasizing its ACTT-1 trial as the “gold standard” regarding remdesivir’s value for COVID-19.
As part of an ongoing series of “Expert Perspectives”, Dr. Leon Henderson-MacLennan, Medical Advisor to inDemic Foundation and inThought Research, discusses the role of thromboembolic disease in COVID-19, and its implications for developmental therapeutics. Dr. Leon Henderson-MacLennan describes the rationale for conducting randomized, placebo-controlled trials on anticoagulants and anticomplement agents for COVID-19 associated thromboembolic disease, and highlights several agents and mechanisms of action to watch closely.
In the midst of growing public and scientific concern regarding the integrity of clinical trials for COVID-19 vaccines, Moderna publicly released its 135-page clinical study protocol. Of biopharma companies with a COVID-19 vaccine candidate in phase 3 trials, Moderna is the first to publicly release its study protocol. The overall goal or primary endpoint of the Moderna’s phase 3 trial is to show that mRNA-1273 has a vaccine efficacy (VE) of 60% in preventing COVID-19. In biostatistics parlance, the VE is [1-HR], or 1 minus the hazard ratio. That is, the goal is to show that healthy participants who receive Moderna’s vaccine are 40% as likely to develop COVID-19, compared to participants that receive placebo. In the trial, a case of COVID-19 is defined as:
“It was the best of times; It was the worst of times”
COVID-19 has forced a re-think of clinical trial design, enrollment, and execution. Among the challenges of clinical trial investigators are the ethical principles of compassionate (“off-label”) use of investigational therapies vs. randomized, placebo-controlled trials [1-2], as well as the logistical challenges of manufacture and distribution of investigational therapies .
Here, we discuss a peculiar and paradoxical challenge of clinical trials accrual in a pandemic. For any clinical trial – whether it be for cancer, Alzheimer’s disease, or diabetes – identifying and enrolling patients is a well-known challenge. For example, targeted therapies for cancers may enroll patients with rare mutations, who may be difficult to identify and to enroll onto a clinical trial at a limited number of cancer centers . It is peculiar that, as millions of patients are infected by SARS-CoV-2, that there are insufficient patients for clinical trials, whose accrual goals are typically a few hundreds of patients.