A Closer Look at FDA’s Proposed Rule on Informed Consent Waivers

Clinical Researcher—February 2019 (Volume 33, Issue 2)


Robert Barton




The U.S. Food and Drug Administration’s (FDA’s) proposed rule to allow an institutional review board (IRB) to waive or alter informed consent requirements in low-risk clinical trials is a good step toward streamlining the approvals process for drugs and medical devices, but the strategy is not without some potential pitfalls, according to several industry experts.

The proposed rule is controversial, according to Dr. Beverley Lorell, senior medical and policy advisor at https://azithromycin.net for the Washington, D.C.-based law firm King and Spaulding. The reason for that controversy has to do with the nature of FDA-regulated efforts on drugs and medical devices versus the broader spectrum of human investigations covered by the “Federal Policy for the Protection of Human Subjects”—more commonly referred to as the Common Rule—which was published in 1991 and codified in separate regulations by 15 federal departments and agencies.

“FDA regulations are much narrower [than the Common Rule],” Lorell said. “Those who are concerned about [the proposed regulation] are concerned that…since FDA regulations are solely focused on a human subject receiving an investigational drug or medical device, almost by definition that investigation does not meet the criteria of ‘no more than minimal risk.’ That is the concern that some people have about applying the waiver of consent to [FDA-regulated] clinical research.”

Who Can Do What to Whom Now

Currently, according to an article in the National Law Review, the FDA allows IRBs to waive or alter informed consent requirements in only a few circumstances, including:

  • Emergency use, which applies when human subjects:
    • Have a life-threatening condition
    • Suffer from a severely debilitating condition
    • Have a condition for which there is no standard acceptable treatment available
    • Are in a situation in which there is insufficient time to obtain IRB approval
  • Planned emergency research, which applies when human subjects have a life-threatening medical condition that requires urgent intervention and cannot provide informed consent because of their condition. In addition, the research must involve an investigational product that has the prospect of direct benefit to the patient and must be administered before informed consent can be obtained. The research must also show that there is no reasonable way to identify eligible participants.
  • In vitro diagnostic device studies using leftover human specimens that are not individually identifiable. The process for waiving informed consent is subject to a number of requirements aimed at the preserving the anonymity of the person from whom the specimen was obtained.
  • When the subjects are U.S. Armed Forces personnel, which would apply only if the U.S. president waives informed consent for military personnel for the administration of an investigational product to members of the Armed Forces.

Who Might be Able to Do What to Whom Soon

Under the proposed rule, the FDA could permit IRBs to waive or alter clinical trial informed consent requirements for drug and device studies, if the IRB find and documents four key criteria:

  • The clinical trial must involve no more than minimal risk to subjects.
  • The waiver or alteration of informed consent will not adversely affect the rights and welfare of the subjects.
  • The clinical trial could not practically be conducted without the waiver or alteration of consent.
  • When appropriate, the IRB will provide the subjects with additional pertinent information after participation in the clinical trial.

“I think it’s a great idea,” said David A. Borasky, vice president of IRB compliance for the WIRB-Copernicus Group. “Human subjects research has been out of step with the Common Rule from the beginning.”

The FDA proposal is just part of an overarching effort—spurred in large part by the signing into law in 2016 of the 21st Century Cures Act, which was designed to help accelerate medical product development and bring innovations and advances to patients who need them faster and more efficiently—to streamline and speed up the approval process for the development of drugs, biologics, and medical devices.

Advantages to Taking a New Approach

“Typically, you wouldn’t want to waive the requirements for informed consent,” Borasky said. “However, the research landscape is changing. The FDA has expressed interest in seeing studies that involved the collection of real-world data to contribute to real-world evidence.”

For example, Borasky said, there is an increasing amount of data available from drugs and medical devices that have already been approved and are on the market. “Under current FDA regulations, you have to go through some funny contortions to be able to waive consent,” he said. “It’s about time FDA gets on board with this. It opens up the possibility to doing a lot of research on things like existing information in medical records that could potentially impact the labeling of currently approved drugs and devices.”

The FDA has been consistently saying for some time now that having access and seeing research with that sort of data being used is important to them, Borasky added. “It’s sort of a treasure trove of information about what happens once these devices and drugs are approved and out on the market, and actually being used outside the narrow confines of a clinical investigation or clinical trial,” he said. “It allows this important research to go forward without adding unnecessary regulatory burden and without putting [anyone] at risk of harm by allowing access to this information.”

This type of activity is fairly common outside FDA-regulated research, Borasky pointed out. “Outside the scope of the FDA, there are all kinds of research projects that are done under the Common Rule regulation with full waivers of informed consent all of the time, because they don’t involve actually interacting or intervening with anybody. It’s looking at old medical records and abstracting data out of them. And that’s the most typical scenario I think that we’re talking about here. So, I don’t know that there are any actual disadvantages.”

In addition, Borasky stressed that the IRBs, not researchers, are the ones who get to make the call on waiving informed consent. “IRBs still have to approve these waivers and document that they have granted that waiver of informed consent, and those four criteria, I think, in practice have proved sufficient. It starts with the idea, first of all, that it has to be minimum-risk research, so, again, you’re not going to be initiating a clinical trial giving people an investigational drug and doing it with a waiver of informed consent and not telling them.”

Modernization and Harmonization

Lorell agrees that there is a school of thought in the industry that there are certain instances in which easing the informed consent rules could be helpful. “Proponents [of easing informed consent] believe there are, on occasion, certain types of FDA research where clinical studies are subject to regulation where the application of the ‘no more than minimal risk’ criterion could be beneficial,” she said. “An example of that might be FDA research that uses biological specimens from human beings.”

Another example might be certain kinds of cluster studies where researchers would be looking at already approved products and assessing outcomes. “In a nutshell,” Lorell said, “it’s the argument that not all FDA-regulated research involves the application of a high-risk, new medical device or high-risk, new drug or biological product to a patient or controlled subject.”

Other arguments center around ongoing efforts to harmonize FDA regulations and the Common Rule, as well as the intent of Congress when it passed the 21st Century Cures Act, Lorell said. “The third major argument is that, basically, the 21st Century Cures Act in 2016 not only gave very explicit permission to the FDA to modify its regulations, but was probably a mandate to do so,” she noted.

Further, Lorell believes the criteria listed by the FDA in its proposed rule to allow the waiver or alteration of informed consent are adequate to protect the rights and health of clinical trial subjects. She pointed out that both the FDA and it parent U.S. Department Health and Human Services define the “no more than minimal risk” standard identically in their respective regulations as constituting “harm or discomfort that are not greater than ordinarily encountered in life.” That’s the approved criterion, and that’s probably the most important one,” she said.

However, Lorell pointed out that IRBs are also going to have to consider the other criteria listed in the proposed rule, including that the waiver or alteration won’t adversely affect the rights and welfare of the subjects and that the research could not practicably be carried out without the waiver or alteration. Adding that the latter is especially open to interpretation, Lorell said “That’s been the subject of a lot of controversy over the years. What does that actually mean? It’s not [coming from] from an administrative point of view [that gaining consent is a hassle], but [from the viewpoint] that if you didn’t have the waiver, the effort to get consent would actually bias the outcome and the conduct of the study.”

Part of a Greater Whole

Indeed, the proposed rule is another example of a trend in which the FDA has been moving more toward a risk-based system, said Darshan Kulkarni, vice president of regulatory strategy and policy at Synchrogenix. “There are multiple instances where the FDA has actually done work [concerning] waivers for informed consent,” he said. “This is just another step in that direction, so I don’t see it as a departure from what the FDA has been doing,” but more of a continuation.

Meanwhile, the FDA’s proposed rule has some clear advantages, Kulkarni said: “The obvious advantage to waiving informed consent is that it speeds up the process a little bit, and the informed consent waivers are really being used in minimal-risk types of products.”

However, Kulkarni cautioned, IRBs should keep in mind that there are other requirements and regulations on not just a local, but a global, scale—such as the General Data Protection Regulation (GDPR) in Europe—which could apply despite the receipt of an FDA waiver or alteration.

“I think that the piece that people might forget is that just because you don’t need informed consent doesn’t mean that you aren’t [affecting] people’s privacy,” he said. “So, you may still want to get privacy waivers when you’re doing that. Usually, you’d incorporate that in an informed consent in many cases, but you may still be collecting retrospective data or certain types of prospective data, and that might require that people be informed that you’re going to be using their data.”

Even within the United States, IRBs will need to be cognizant of state and federal laws related to data privacy. “That is one of the things that I think is going to be important as you continue,” Kulkarni said. “I mean, California is doing its own version of GDPR, and there are various both federal- and state-level privacy laws that are implicated. So, in the bigger scheme of things, what have we really achieved? We’ve just gone from reviewing one document to reviewing another document.”

Subject to Change

The proposed rule is “a good start,” Kulkarni said. “I think the FDA is still evaluating what would really happen. This is just in proposed format, anyway. Chances are that people will comment, and there might be additional pieces [to come]. It might just be a change in wording, but it might become more inclusive as we continue [toward this risk-based system]. I think it’s just important to recognize the larger areas at play.”

Kulkarni also pointed out that FDA Commissioner Scott Gottlieb can be expected to address such issues within the framework of the Trump administration’s overall regulatory and policy goals. “The Trump administration came in and said, ‘We want to reduce the cost of drugs, we want to minimize the regulations that get applied,’” Kulkarni said. “[Gottlieb] came in, and he’s trying to match those thoughts and he’s trying to, again, match what the administration wants to achieve. This is very much in line with the administration’s thoughts in that they are reducing the number of implicated regulations and reducing the amount of red tape that you have to go through, and still balancing the needs of people who may very well need consent.”

One area that does raise some level of concern is that of medical devices, Kulkarni said. He pointed out that, in the area of health information technology, the FDA has chosen not to review software, and now the proposed rule to ease informed consent raises some questions about the implications for the approved product. “That’s a worry for me, as we continue,” he said. “Not drugs, because I think that the drug world, for the most part, is conservative around these regulations. There are a lot more Wild West–type plays in the medical device world.”

In general, the process that will play out under the rulemaking procedures will require IRBs to determine just how to apply the FDA rule in practice, as opposed to theory, according to Lorell. “I think the IRBs are going to have a learning curve,” she said. “At one end of the spectrum will be research, such as federally regulated research on leftover biological specimens. At the other end of the spectrum will be something like a permanently implanted medical device or a drug with known life-threatening side effects. There’s going to be a whole lot in the middle between those goal posts.”

Robert Barton is a freelance writer based in Virginia.