Announcer: From the National Institutes of Health in Bethesda, Maryland this is All About Grants.

Megan: Welcome to another edition of All About Grants. I’m your host, Megan Columbus, coming to you from the NIH Office of Extramural Research. Today we’re following up to our last podcast addressing human subjects in your research application by talking about requirements for inclusion of women, minorities and children in clinical research. We have with us today Dr. Della Hann from the NIH Office of Extramural Research. Can we start with why does NIH have inclusion policies?

Della: That’s a good question. I would say if you wound the clock back to the early 1980s we didn’t have these policies. But there was growing recognition, both in the advocacy community, as well as Congress, and actually by scientists, as well, that sometimes our research portfolio really wasn’t matching the needs of the larger populations. The first area that drew attention had to do with the inclusion of women and minorities in research. That whole idea began in the 1980s, first as a policy, and then it was followed up in the early 1990s with a congressional mandate, actually, in the NIH Reauthorization, that NIH be sure that its research portfolio, in general, was addressing the health needs and issues for women and minorities. It left the implementation up to the NIH, but it was very much concerned with the clinical research portfolio. Then later on in the 90s, the policy for the inclusion of children came along, too. That actually grew out of concern that much of our research, by not including children, we were applying treatments and methods of intervention that had been tested on adults only. And we were therefore extrapolating and applying that information to children, and sometimes that had good consequences, sometimes it didn’t. And they just felt that it was important that NIH also wake up and take advantage of that population in terms of trying to understand new treatments.

Megan: Could you talk a bit about the definition of “children” and the definition of “minorities”? I’m assuming that we can understand the definition of a “woman”.

Della: I hope so! The NIH turned to the American Academy of Pediatrics and sought advice in terms of how they would go about defining “child.” And I will admit that there is often discussion and debate on this topic and it may be something that could be revisited in the future. But for now, it essentially extends from the time of birth until the age of 21. The definition of “minority” actually is an interesting one, in that if you even look at the way the United States over the years has classified people of different racial and ethnic backgrounds, it very much changes over time. And in fact, if you remember filling out your census this last summer, you would have seen that the categories that we had to choose from for describing ourselves was very different than the categories that we had ten years ago. So the Office of Management and Budget, however, does go through periodically and sort of set up standards, sort of standard classification systems. It then requests that the rest of the government also follow. And those are the categories currently that NIH follows. So the categories that were provided by the Office of Management and Budget (OMB), back in 1997, they produced their last revision, and those categories include American Indian or Alaska Native, Asian, Black or African American, Native Hawaiian or other Pacific Islander, and White. What they did do also during that period of time was they also made a distinction that those were the racial categories, and they then set up two different ethnic categories: Hispanic versus non-Hispanic. And so technically, then, an individual would go through and you would have two questions to answer: What ethnicity are you? And you would choose Hispanic, non-Hispanic, and then it would be followed up with, what racial category do you consider yourself to be part of? And you can choose one or multiple ones according to the OMB directives.

Megan: You’re required then to address the inclusion of these populations in your application. What might be acceptable reasons for not including one of the populations that’s covered by the policies for your research?

Della: So I’m going to take them separately because really the bottom line is the kind of science that you’re proposing. So if I am looking at a highly experimental, invasive pharmaceutical, it hasn’t hardly even been tested yet, even in humans. The probability of being able to do that in a child right off the bat is virtually non-existent due to ethical considerations. So that would be a legitimate scientific reason for not including children in that particular study. Similarly, if I’m interested in prostate cancer, it would probably be very unlikely that I would be studying women, and that too, would also be acceptable. Sometimes because the way we have done our research over the past is indicated that there have been individuals and groups, or not individuals, there have been groups essentially that have not been studied very thoroughly. And it’s documented by looking at the literature to say, Oh my goodness, we’ve been doing research on—name a topic—for a number of years; however, we haven’t really been closely looking to see if there are differences according to people’s racial background. And we really think it’s important to carve out and look very in depth at Black Americans, or Hispanic Americans, or Asian Americans, etc. So you can make the case, essentially, with your science, in terms of the scientific question.

Megan: Would difficulty recruiting a particular segment of the population be a valid reason for not including them in your application?

Della: Generally, no. And I say that in terms of “generally” because it also has to determine with the size of the research project that you’re suggesting. So if you’re coming to the NIH and applying for a very small grant, for the money that you’re receiving for that grant, it would not be feasible for you to reach out and have a broad network across the country in order to have representation from a variety of different groups of people. However, that shouldn’t stop you from within your given community to doing your very best. It’s just that we also know that some communities have a preponderance of certain kinds of populations. So it all has to be sort of weighed out in terms of, again, the question that you’re asking and the size of the grant that you’re looking for. But in general we try, as program people here at NIH, to really suggest that people really think this through and think through the kinds of groups that are available even within their communities.

Megan: And I assume that within the application you should be very explicit about your rationale for including or not including any given population?

Della: That is correct. It bodes well for you to think through that information and to have it in your section on inclusion.

Megan: So the application requires plans for outreach and recruitment. Do you have any advice for applicants about the level of detail that’s expected there?

Della: Again, it really depends. I will admit that, based off of the kinds of science that I used to have in my program portfolio, I would try to really make my folks think through those issues. Recruitment sometimes can be very difficult. Anybody who works with human subjects knows that. And just because that’s the way you’ve always done it doesn’t necessarily mean it’s the only way to do it. Very often there are resources within one’s community; it’s just you have to reach out in order to identify them.

Megan: So it sounds like there’s a recommendation for networking with investigators who already do this kind of research at their institution, in their communities. Anyone else they should talk to in particular?

Della: Again, I think it depends on the kinds of research that you’re doing. So you might, for example, way back when, when I was doing my own research, I worked a lot with the local Health Department, because I was interested in the populations that would frequent the public clinics. So they just became a natural partner for me to work with. And I think that’s the kind of thinking that people have to go through in terms of knowing their population and understanding their communities to understand who else might have an interest in working with those groups and to see if you can partner with them.

Megan: In the application there are enrollment tables. What’s the expectation for the accuracy of the predictions of those enrollment tables? How closely are they scrutinized by the reviewers?

Della: Actually, they can be pretty closely looked at. It is quite possible for people to review that section and to not find it adequate. And to make comments then in the review. And actually to downgrade the application a bit in terms of it not being sufficient for the kind of research that you’re proposing to do. So let me give you an example. If I were doing research looking at infant health issues, and I was working in an inner city here on the East Coast, yet my tables reflected that it was going to be 80% White, I think people would sort of look at that and say, What are you thinking about? Usually inner city populations are much more culturally diverse, and so the fact that it was skewed that way, again, unless you had a scientific reason—there were genetic predispositions that you were looking for or something that would give you an epidemiological basis for why you would be wanting to tilt your sample in that way—I do believe, that as a reviewer, you’re likely to comment on something like that. So it’s a balance. It’s a balance of the scientific question, where the person’s located, the size of the application. But reviewers do pay attention to it and can make some rather strong comments about whether they find it acceptable or unacceptable.

Megan: If you’re way off after being awarded, does the NIH take action?

Della: It’s possible. It is possible. Again, this is a policy and for the inclusion of women and minorities it’s actually a law. And some of the institutes for certain areas have very much focused on insuring that the diversity plans are matching their targets as closely as possible. If not, usually the first line of concern comes from the program officer—having a conversation, strategizing. If it continues and it clearly is really off the mark, it would be possible, in terms of following the Grants Policy Statements and so forth, to actually withhold funds, or potentially even to terminate an award early if the institute really felt that the science was not being justly served because the inclusion was so far off.

Megan: Getting back to the application process for just a moment. If an application’s inclusion plans are deemed unacceptable, is there any way that that application can still be funded?

Della: Yes. So if a peer review group has found the plans to be unacceptable, and the application comes back to the institute for consideration for funding, and there is a strong desire in the institute’s part to do that, then the program officer will have a conversation usually with the PI of the application, discuss the points that were made by the peer reviews in terms of why it was unacceptable, and usually work with the investigator to get a revision to that plan. Then that revision comes to the institute that’s considering the application for funding and determines whether or not it meets acceptability. The bottom line is that an application with an unacceptable plan will not be funded.

Megan: But as long as it got a good enough score during the peer review process, it doesn’t have to go back and get re-peer reviewed.

Della: That’s correct.

Megan: Is there anything else that you think might be of interest to our listeners?

Della: Really what this is after is we want to make sure that the science, as a whole here at the NIH, truly is generalizable to the populations that we say our science is supposed to be generalizable to, and you can’t do that unless you actually involve those people in the research.

Megan: Thank you for joining us today. For NIH and OER, this is Megan Columbus.

Announcer: For more information on inclusion in clinical research, visit the OER homepage at grants.nih.gov and search for “inclusion of children” or “inclusion of women and minorities.”