Most research is conducted with informed consent, a process that allows to the prospective participant to learn about the study through discussion with the investigator or study staff and to decide if participating is right for them. Yet, there are exceptions. In limited and strict circumstances, federal regulations governing human subjects allow for alterations or even waivers of informed consent. (Adobe Stock)
by Varshini Chellapilla
Most clinical trials are conducted in highly controlled environments to study the efficacy of a certain intervention. But the world we live in is often much messier than that.
This is where pragmatic trials come in. Pragmatic trials are designed to study interventions in circumstances that closely approximate actual clinical practice as closely as possible. Some pragmatic trials include subjects who may not know that they are part of a clinical research.
Research conducted by Penn Program on Precision Medicine for the Brain Researcher Emily Largent, PhD, JD, RN, and Stephanie Morain, PhD, MPH, an assistant professor at the Center for Medical Ethics and Health Policy at Baylor College of Medicine, looked at the data on public attitudes toward consent for pragmatic trials. The resulting article, published in The Hastings Center Report on April 11, was titled “Public Attitudes toward Consent When Research Is Integrated into Care—Any ‘Ought’ from All the ‘Is’?”
“In order to make research as much like normal life or regular clinical practice as possible, it is often the case that we want to conduct the research without getting informed consent from participants,” Dr. Largent said. “Because once we tell people they’re in research, that can change what happens and who participates.”
The research was funded by the NIA IMPACT Collaboratory, a national infrastructure that aims to promote pragmatic clinical trials of interventions within the healthcare system. Dr. Largent serves as the associate core leader of the Ethics and Regulations Core of the Collaboratory. Penn Memory Center Co-Director Jason Karlawish, MD, is the core leader.
Pragmatic clinical trials are conducted to study certain interventions or phenomena in real-life conditions. The goal is to test hypotheses in everyday life to the greatest extent possible, and allow researchers to evaluate how particular interventions function in common clinical practices. For this reason, they are often conducted where patients are already receiving their care.
Most research is conducted with informed consent, a process that allows to the prospective participant to learn about the study through discussion with the investigator or study staff and to decide if participating is right for them. Yet, there are exceptions. In limited and strict circumstances, federal regulations governing human subjects allow for alterations or even waivers of informed consent. In these cases, the study must not pose greater risks that people encounter in daily life, it should not threaten their rights or welfare, and it should not be possible to conduct the research unless there is a waiver of consent.
For example: In 2019, Dr. Vincent Mor, the Florence Pirce Grant University Professor at the Brown University School of Public Health and a co-leader of the IMPACT Collaboratory, utilized pragmatic trials to determine the effect of music on a person’s memory and cognitive function. People with Alzheimer disease and related dementias may experience agitation or exhibit aggressive behavior during the later stages of the disease. To address these behaviors, Dr. Mor and his team provided residents in a nursing home with recordings of music they listened to when they were younger and observed the effect on their behavior and cognition over time. This is an example of the kind of low-risk study that might be eligible for an alteration or waiver.
But how do people who could potentially become subjects of pragmatic research feel about waivers and alterations of consent?
Drs. Largent and Morain reviewed the results from five nationally representative surveys, with more than 10,000 participants total, and two deliberative engagement studies that previously sought to describe public views on approaches to consent for pragmatic trials. They found that most people accepted streamlined consent, which is an abbreviated version of informed consent, for pragmatic trials as opposed to forgoing the trial itself.
However, there are certain trials that can only be conducted with a waiver of consent. “What we ended up finding is that a lot of people, once you explain to them that the research can’t be done otherwise, feel like it’s a reasonable trade off to sacrifice some aspects of consent, so that the important research can go forward,” Dr. Largent said.
In these cases, Drs. Largent and Morain argue that waivers should only be considered when there are no other alternatives. Evidence suggested that a majority of the public was willing to accept waivers of research consent for studies that they believed had a high social value.
The Federal Policy for the Protection of Human Subjects issued by the Office for Human Research Protections allows waivers and alterations of consent requirements for pragmatic trials once certain criteria are met. The research 1) has to be of minimal risk, 2) cannot be conducted without the waiver, 3) does not affect the rights and welfare of the subjects, 4) cannot be conducted with anonymized data, and 5) allows for subjects to be informed at an appropriate time. An institutional review board is created to regularly assess the ongoing trial.
“However, there are still a few people who are not comfortable with this idea,” Dr. Largent said. “And, then, that really becomes the ethical challenge: If we know that people aren’t comfortable with research conducted without their informed consent, how do we advance the science?”
Drs. Largent and Morain argue that when a trial has very high social value and can be conducted in no other way, waivers of consent can be justified, even though there may be some people who would be uncomfortable with that.
Over the last decade, pragmatic trials have gained a lot of attention because they allow researchers to broadly generalize the results of their research under real-world circumstances, and contribute to the improvement of health care delivery and public policy.
“What we know, unfortunately, is that persons living with dementia and their caregivers have a lot of needs, and often we don’t have good evidence-based solutions to meet those needs,” Dr. Largent said. “So, the hope with these pragmatic trials is that we can improve care for these individuals by understanding how certain interventions function in the real world, outside of the nice and tidy circumstances of a traditional trial.”