Research Ethics

By Alex John London and Jonathan Kimmelman

Science, April 23^rd, 2020

Summary by Eman Mubarak (MS2)

With the huge influx of research dedicated to developing treatments for COVID-19, this article addresses the harmful perception that in a pandemic situation, rigorous experimental design is a luxury. The authors point out some examples of research that would otherwise be considered of poor quality that has been allowed a “pass” in this pandemic. They outline three problematic assumptions that lead to such research exceptionalism:

1) Evidence that can be generated sooner, even if flawed, is preferable to evidence that takes longer to materialize but demands more resources. This results in an increased probability of false leads, which end up consuming already scarce resources, as well as delayed adoption of interventions that do turn out to be effective.

2) Key features of rigorous research, such as randomization and placebo comparators, are in conflict with the ethical obligations that clinicians have to their patients. In fact, appropriate studies ensure that no study participant receives a standard of care that is known to be inferior to any available alternative.

3) Researchers and sponsors are free to exercise broad discretion over the organization and design of research. This introduction of bias effectively undermines regulations and reporting guidelines that give research its social and scientific value.

The authors argue that a global emergency should in fact place a heightened responsibility on stakeholders to uphold core research principles and generate data that is robust and reduces uncertainty. So, what are the ethical obligations of researchers in this pandemic? The article describes five conditions that clinical trials should embody:

1) Trials should address key evidence gaps.

2) Trials should be designed to detect clinically meaningful effects so that both positive and negative results serve the informational needs of clinicians and health systems.

3) Designs should be pre-specified in protocols, prospectively registered, and analyzed in accordance with pre-specification.

4) Trials should be reported completely, promptly, and consistently with pre-specified analyses.

5) Studies must be feasible in terms of reaching their recruitment target and being completed within a time frame where the evidence is still actionable.

The article calls for enhanced collaboration, division of labor, and triaging out low-value and duplicative research during this crisis. Expeditious research is feasible, but “crises are no excuse for lowering scientific standards.”

H. Clifford Lane, MD, Hilary D. Marston, MD, MPH, and Anthony S. Fauci, MD

Clin Trials, February 26^th, 2016

Summary by Eman Mubarak (MS2)

This next article comes from the NIH and discusses the ethics of clinical research more broadly. Using examples from the HIV/AIDS and Ebola epidemics, the authors lay out several core scientific and ethical principles that should guide the testing of medical countermeasures in an outbreak setting:

Ethical conduct to avoid exploitation of trial participants or local research partners: This includes respect for volunteers and study communities, the importance of informed consent, and collaboration.

Partnership with affected country investigators and officials: In the case of the Ebola outbreak, it was important to build sustainable research infrastructure in Liberia after assessment of needs and identification of interested local investigators.

Scientific validity: The interventions studied must have plausible benefit, and trial designs need to be scientifically sound.

Independent review and scientific oversight: An independent and skilled Data and Safety Monitoring Board, including representation from a range of experts, should meet on a regular basis and determine whether the trial should be modified or if it can be continued.

Transparency: Data should be shared promptly regardless of the outcome. Publication should not delay dissemination of findings and potential changes to clinical and public health practices.

With these guidelines in mind, stakeholders can increase the likelihood of success in research and reduce the chances of inadvertent harm.