The FDA seeks to apply risk-based profiles to enable institutional review boards (IRBs) to waive or alter what can be stringent requirements for obtaining informed consent for certain clinical trials involving minimal risk to participants. The proposed changes represent a material deviation from the current IRB informed consent requirements and could bolster clinical trial efficiency for IRBs and clinical investigators participating in what would be classified as minimally risk clinical trial.
TrialSite News provides an overview of this action that was reported some months ago.
Titled “Institutional Review Board Waiver or Alternation of Informed Consent for Minimal Risk Clinical Investigations,” the FDA issued last year seeking comments by January 2019. These policy changes seek to change how informed consent is collected for what would be considered minimal risk participants.
Current Regulations and Purpose IRBs
As reported in Policy & Medicine, exceptions for obtaining informed consent can only be made by life-threatening scenarios or when conditions for emergency research are met. These are the only conditions today where informed consent can be waived.
IRB’s have been established as legally responsible for the review, approval, and continuing review of clinical investigations. They must ensure that clinical investigators follow the rules and appropriately obtain a study participant’s legally effective informed consent prior to the participant’s participation in a clinical trial. There are current exceptions as noted above including 1) Emergency Use and 2) Planned Emergency Research 3) In Vitro Diagnostic Device Studies Using Human leftover Specimens not individually identifiable and 4) Armed Forces Personnel.
A Reminder: Why do We have Informed Consent?
The underlying foundation for informed consent can be traced back to Nazi Germany and criminal experimentation done during World War II. Hence, the Declaration of Helsinki was procured, which represents a set of ethical principles regarding human experimentation developed for the medical community by the World Medical Association. Widely regarded as the cornerstone of research ethics, it is not legally binding but surely draws an authority from the degree to which it has been codified in and influenced national or regional legislation and regulations.
Prior to the 1947 Nuremberg Code, there was no generally accepted code of conduct governing the ethical aspects of human research, although some countries, notably Germany and the Soviet Union (now Russia) had national policies. The Declaration offered ten principles first stated in the Nuremberg Code and tied them to the Declaration of Geneva in 1948; a statement of physicians’ ethical duties. The Declaration mode specifically addressed clinical research reflecting on the practice from the term human experimentation used in the Nuremberg Code. There was a relaxation of the conditions of consent, which was “absolutely essential” under Nuremberg. The declaration has been updated with modernized conditions.
The Proposed Changes
Under the FDA’s proposed rules, IRBs are granted flexibility and ultimately power to determine waiver decisions. Under the proposed rule, the IRBs, in order to waive informed consent, must find:
- The research involves no more than a minimal risk to the subjects
- The waiver or alternation will not adversely affect the rights and welfare of the subjects
- The research could not practicably be carried out without the waivers or alterations
- Whenever appropriate, the subjects will be provided with additional patient information after participation
In a powerful example of executive branch agency rule making (quasi legislation) with what could be profound implications depending on the circumstances, the drug development landscape could be significantly transformed.
FDA Commissioner Gottlieb on the Proposal
As clinical trials become more complex, expensive, and tailored to sophisticated advanced therapies, the expense, duration and risks rise for both sponsor and investigator. Hence, Gottlieb notes that after years of sponsor and clinical investigator feedback concerning stuck research initiatives, even in minimally risky scenarios, that lots of potentially life saving treatments (not to mention enormous economic loss) has resulted. Moreover, the agency lacked the authority to permit a waiver of informed consent for specific research.
Under the passage of the 21st Century Cures Act, the FDA’s authorities became more flexible and stronger. Due to the legislative imperative, the agency seeks to expand its reach via executive branch rulemaking and guidance. They seek to use newfound powers, with all the best intentions, to support clinical research program flexibility with the hopes that drug makers and investigators can accelerate research and development to offer more and better treatments and hopefully cures where there is “minimal risk to the patient.”
Flexibility and Progress is Good: But Lets Keep an Eye out
We at TrialSite News are all for flexibility. Clearly the intentions are good and the authority is there for this kind of incremental (but significant) modification to informed consent rules. The fact is that the biopharmaceutical industry is stuck in many risk-averse and antiquated processes based on the “CYA” model dealing with the rules, regulations, and stiff penalties they face if there are violations of these rules and law.
It is the underlying systematic herd-like behavior of humans that we get concerned about. For example we have covered a number of informed consent breaches under existing laws from unsuspecting patients being injected with Ketamine as part of an “emergency” experiment to a university where a rogue investigator was signing up children without securing informed consent. We have a worldwide focus and therefore, take a global view. When we look abroad we get just a little spooked—such as in South Africa where studies show today’s informed consent rules aren’t enough and in China where “political prisoners” that are actually, by many credible accounts, oppressed groups (whether ethnic minorities or those critical of the government) are often rounded up and when executed for crimes against the state their organs are conveniently taken for a vast global market.
Locally, where we think we have evolved past most unethical behavior, we still must be vigilant. There are areas we must monitor carefully. For exampl,e many IRBs are now not non-profits or part of academic centers but for-profit vehicles funded by large private equity groups seeking double-digit returns over a period of time. In fact, there has been a wave of private equity-led IRB investment that had led to considerable consolidation. There is nothing wrong with this. The pursuit of growth, profits and value accumulation is a fundamental part of our underlying Western democratic and economic system. We even know some principals that stand to gain tremendously from such wealth generation—more power to them.
It is just when “herd” mentality finds a loop hole and runs with it that ethics can be lost for the bigger prize of profits. The Financial Crisis of 2007-09 is a great example where loopholes helped all involved—from attorneys to credit agencies to accountants to the banks themselves find the excuse to pump toxic debt worldwide. It wasn’t an individual thing—it was a systemic thing.
The Part of Adam Smith’s Invisible Hand that Few Know About
Many free market proponents point to the “invisible hand of the free market” that ensures markets function in a rational manner. This is often an underlying premise for those that want less governmental oversight and more “liberalized” policies resulting in deregulation. The FDA’s move to liberalize informed consent, in a way, is part of this process. Let the industry be the judge to determine what is risky and what is not for purposes of determining when informed consent is required.
Of course, in Adam Smith’s Western free market treatise Wealth of Nations, he does discuss often self interest as an important human agency and that the invisible hand does in fact show up Smith himself was no laissez faire ideologue often directly stating the need for regulations as Smith also argued that anytime businessmen meet together they are likely to conspire against the public good.
Back to the primary point: flexibility, agility and creativity are a great thing for IRBs but also ensure they (and all else) are monitored that the rational for the new exceptions for informed consent waivers are used for the public good versus self interest.