Belmont Report: Are changes needed?

OHRP director discusses its successes

[In this Q&A, Bernard Schwetz, DVM, PHD, director of the Office of Human Research Protections (OHRP), discusses the Belmont Report’s successes and challenges as the 25th anniversary of its launching has passed. To see excerpts from the Belmont Report, click here.]

Question: What do you believe are the two biggest accomplishments in human subjects protection that were achieved in the past 25 years because of the Belmont Report?

Schwetz: Well, I think one of them has to be to keep the focus of human subject protection on ethics and not just science or regulation. The fact that the Belmont Report was very clear in articulating the need to adhere to the three ethical principles, I think has created a framework for conducting research involving humans in a way that has modulated the field so that we can continue to focus on those principles, rather than wandering all over and trying to identify a basis for protecting subjects. That clearly has to be No. 1.

I think the second factor that has created an environment for doing research that keeps the focus on protecting human subjects is the whole IRB system, the institutional review board. The regulations by themselves are important, but if you don’t have a body of people within the research community to make sure the regulations are being followed — and that’s the IRB network that we have — the regulations by themselves wouldn’t be worth much, especially in this kind of system where compliance is voluntary. The whole thing is a system of trust, and the IRBs throughout the research community give credibility to the trust within the system.

Question: On the other hand, where have the Belmont Report’s ideals fallen short in research practice?

Schwetz: There are issues we’re struggling with today that were not issues back in the middle ’70s, and one example I would give is conflict of interest. Conflict of interest wasn’t mentioned in the Belmont Report because at that time it had not surfaced as the particular issue it is today. That would be an example of issues that are a reflection of the time as opposed to ethical principles that cut across the whole field of research.

What’s interesting is I had the opportunity to interview many of the members of the national commission and the support staff who helped to put together the various commission reports. One of the things I asked them all is, How up to date do you think the Belmont Report is? Does it have to be rewritten?’ Despite the fact that there are issues like conflict of interest that weren’t specifically addressed in their deliberations, they all felt the Belmont Report still is a logical basis for protecting human subjects today.

The other issues we’ve dealt with one-by-one by various forms of guidance from the government or nongovernment. So as long as we can continue to use the Belmont Report as a basis for decisions and provide guidance on specific issues, I think we’re better off to leave it just as it is.

Question: You’ve touched on an issue that some people have mentioned, and that is whether it would be helpful for the government to appoint a new commission to update the Belmont Report since we have so many new types of research, such as genetics research, to deal with today. What are your thoughts on why or why not that would be needed?

Schwetz: There is a federal advisory committee on genetics research. So I think that kind of federal advisory committee handles the questions that relate to new technology and new science. From that standpoint some of these new issues are being taken care of by the federal advisory committee on ethics. We have the federal advisory committee on human research protections. So I think there is an alternate mechanism that has been put in place to deal with the new issues. The one that deals with genetics is one that I think that even if we rewrote guidance today, within a period of time we’d have to revisit it anyhow because the technology is changing rapidly enough so that even if you gathered a group of people together, they would only deal with the issues that we have faced yesterday and today, but not necessarily be able to anticipate the ones a couple of years out. So at this time of more rapid change than it was 25 years ago, we’re perhaps better off to deal with this in an ongoing basis rather than to try to anticipate what’s going to be the question for society in 10 years. It would be very difficult to predict.

Question: Another area that we sometimes hear about is that the Belmont Report is a great ideal and it would be fantastic if it were adhered to or even read by every researcher, but there is a lack of understanding of it among many clinical trials researchers, including the ones regulated by the FDA, and also that a lot of privately funded research isn’t subject to the same kinds of ethical considerations that government-funded ones are because they’re not regulated. What are your thoughts on those two concerns about human subjects protection?

Schwetz: In audiences, where it has been asked, How many of you have read the Belmont Report?’ there is always a very high percentage of people who raise their hands. Now I don’t know what the validity of that kind of test is, but nonetheless, my feeling is that the Belmont Report is very widely read because it’s easy to read and it’s short. In contrast the regulations are lengthy and not easy to read, and I think if you were to rank order the documents that have been read by the largest number of people, the Belmont Report would be at the top, the Declaration of Helsinki would be some place below it, and federal regulations would be below that. Just because people go to the federal regulations for specific issues that they need to know. They don’t go there for background. If they need to know a specific answer to a question that deals with prisoners or with children or the IRB structure they go directly to the piece of the federal regulations. By contrast, the likelihood that someone would have picked up the Belmont Report and read it front to back is pretty high.

Question: How do you answer the concern that smaller research centers and private research are not adhering to the same codes that the larger institutions are?

Schwetz: It’s possible that that’s true, but it’s also true that we don’t have a good way of tracking what’s going on in the community research centers because there’s a very large number of them and the efforts to educate the research community have been largely focused on the academic research centers. Now the research is going beyond the academic health center and is going out into the community and private practice and small hospitals, and none of us has the resources to provide training programs locally at all of those sites.

But perhaps as importantly, we don’t have good information about what’s going on at those sites in terms of how well versed they are in the regulations. So we depend, for example if there is a study that’s funded through the University of Maryland, but it’s conducted in a small research site somewhere in the community, we have to depend on the University of Maryland for making sure that people who are collaborating on this study out in the community meet the standards of the University of Maryland. It has to be a partnership between the large health centers where we have spent a lot of effort providing training and the federal government who continues to remind those research sites that regardless of where the research is going on that we all have an obligation to make sure people are well trained.

Question: Could you name a couple of challenges in human subjects protection that remain and is there any effort beginning now to meet these? Specifically, with all of the attention paid recently to the FDA and the problems with Vioxx and antidepressant drugs for children, do you think there is a good chance we’ll soon have a large public registry of all clinical trials, or is there some other type of achievement that might prevent some of the problems that have come up recently?

Schwetz: I’m sure that people within the medical product centers of the FDA are reviewing very seriously how they could help prevent any further problems with drugs being recalled; so I’m sure they’re looking hard at that.

From the standpoint of protecting human subjects, that’s a somewhat different issue. There are things I worry about there: one is the consistency of IRBs; we get a lot of comments back that IRBs are not consistent one to another. And it’s a concern as the research becomes more complicated, and the science becomes more complicated, and the difficulty of obtaining good informed consent becomes more difficult. It’s a concern that IRBs might not be as consistent as we want them to be. They do their jobs to protect subjects based on same regulations, so one of the things we’re trying to get a handle on is how consistent IRBs are and what is the impact of protecting human subjects as IRBs do their work today. We can gather information on the length of time it takes to review protocols and how many cycles it takes to get a protocol reviewed and approved, that kind of information on how IRBs perform. But it’s more difficult to get information on how well IRBs are doing their job, because we don’t have agreed-upon criteria to even measure that.

That’s one of the things that we’re giving thought to and figure out how we might have a better handle on the performance of IRBs.

We’re looking at it within OHRP and we are reaching out to some other groups including the Secretary’s Advisory Committee for Human Research Protections and others within the research community to get some momentum built on trying to take on this issue of how we can measure the performance of IRBs.

Question: Is there anything else about the Belmont Report and our reflecting on it 25 years later that you’d like to discuss?

Schwetz: I’d like to re-emphasize the importance of the ethical basis for our decisions in protecting human subjects. It’s awfully easy to focus on the regulations as the basis for how we make decisions and lose sight of the ethical implications. So one message that I’m trying to get out to the community is that the regulations are important, but the regulations can’t be taken in absence of a continual thought process about the ethics as the basis for our decisions.