The “rights, safety and well-being of the participants are the most important considerations, and should prevail over the interest of science and society.” In other words, “the ends never justify the means.” These are the principles that should guide human subjects research, according to Currien MacDonald, M.D., chair of an institutional review board (IRB) at WCG Clinical.
In discussing the topic at a recent WCG webinar,[1] MacDonald began by explaining there are three components in research studies, and each plays a role in ensuring the safety of research participants—the study site, including investigators and institutions; the sponsor, perhaps in collaboration with a clinical research organization; and lastly, the institutional review board (IRB), research ethics board, if involved, an institutional biosafety committee, the Food and Drug Administration (FDA), and the HHS Office for Human Research Protections.
“The first responsibility of the sponsor is for ensuring that FDA and all participating investigators are promptly informed of significant new adverse events or risks with respect to the drug or important safety information,” said MacDonald, who also contributes to biosafety reviews for WCG’s institutional biosafety committee.
Second, “if the sponsor determines that its investigational drug presents an unreasonable and significant risk to subjects, [it] shall discontinue those investigations that present that risk…notify the FDA, all institutional review boards and all investigators…of this discontinuation,” he said.
Risks: Acceptable or Not?
The sponsor also must dispose “of all stocks of drug” and submit to FDA a “full report of the sponsor’s actions,” MacDonald said, adding that discontinuation must occur as soon as possible “and in no event later than five working days after making the determination that the investigation should be discontinued.” Similar requirements apply to sponsors of device trials, he said.
The sponsors of a drug study may determine that the identified risk is relevant to a “certain” study population, but “the same drug in another study with a different population would not have that risk,” he said. In that instance, “those [studies] may be able to continue,” MacDonald explained.
With a device study, “if the main safety risk is at implantation, then the rest of the study, the maintenance and ongoing of the device…may continue on to ensure that benefits…continue to happen,” he said.
Sponsors also need to comply with the International Council for Harmonization (ICH), which provides “guidance for FDA studies.” Under this, the sponsor’s first responsibility is to “decide which risks to reduce and which to accept and to identify systemic issues that impact subject safety,” he said.
Speaking more broadly, sponsors are “also going to perform an ongoing safety evaluation to promptly notify all investigators” and regulatory authorities, including IRBs, “of findings that could possibly adversely affect the safety of subjects and to expedite reporting of all adverse drug reactions, both serious and unexpected,” MacDonald added.
