>> Dawn Corbett: Hi, I'm Dawn Corbett, the NIH Inclusion Policy officer in the Office of Extramural Research, and today I want to give you an overview of the NIH inclusion policies. Our goals for this session are to understand policies for inclusion of women, minorities, and individuals across the lifespan in NIH research and to recognize additional requirements for NIH-defined phase III clinical trials. And finally, to learn how NIH inclusion policies are addressed when applying for or proposing NIH clinical research. So to start out, I'd like to give you a timeline of our NIH inclusion policies and participant data collection over the years. NIH has had inclusion policies on the books since 1986 when NIH established a policy encouraging researchers to include women in studies. And this policy was born out of concern that women of childbearing age were routinely excluded from clinical research studies. In 1993, Congress passed a public law requiring the inclusion of women and minorities in NIH clinical research, and NIH began its inclusion policies. Beginning in 1998, NIH issued a policy requiring inclusion of children in NIH clinical research. And in 2015, NIH revised the definition of a child. Previously, a child was considered an individual under the age of 21. Starting in 2015, that definition changed to an individual under 18 to better align with the age of consent to research in most states. Then in 2017, Congress passed the 21st Century Cures Act, which included a number of provisions that affected inclusion, including new requirements for reporting results of sex, gender, race, and ethnicity analyses in clinicaltrials.gov. And finally, in 2019, NIH now requires inclusion of individuals of all ages in NIH human subjects research. I'd like to talk now about the inclusion of women and minorities in NIH research. As I mentioned on the previous slide, public law now requires that women and minorities be included in all NIH-funded clinical research studies unless there's a compelling rational for exclusion. What might be a compelling rational for exclusion? Well, the law specifically states that cost is not an acceptable reason for excluding these groups. However, there may be some circumstances when excluding women and minorities may be acceptable. For example, if you're doing a study on prostate cancer, you may exclude individuals whose sex at birth is female because the condition does not occur in this group. And that would be considered acceptable. The law has additional requirements for NIH-defined phase III clinical trials. These trials must be designed to permit analyses by sex or gender, race, and ethnicity. In 2017, the 21st Century Cures Act included a provision that required these analyses be posted on clinicaltrials.gov if you're doing an applicable NIH-defined phase III clinical trial. What's an applicable clinical trial? These are generally drug and device studies that are required to report to clinicaltrials.gov for registration and reporting. The law also states that NIH must support outreach efforts to recruit and retain women, minorities, and their subpopulations, and this is done through outreach that our recipients do to these populations. A few clarifications. I'd like to define a few terms we used in the previous slide. First, an NIH-defined phased III clinical trial is a study that evaluates an intervention in large groups of people by comparing the intervention to other standards or experimental interventions. These are generally large studies, often several thousand, but they can be smaller depending on the condition, that are trying to compare an intervention to another intervention. And they include drug, device, behavioral interventions, community trials, et cetera. I'd also like to talk a little bit about the valid analysis that's expected for NIH-defined phase III clinical trials. Generally, a valid analysis involves investigators stratifying their primary outcome by sex or gender and race or ethnicity. For example, if you're reporting an overall risk ratio, you would provide that corresponding risk ratio in those subgroups. In most cases, high statistical power is not necessary, but the intent is really to inform future studies so that that information can be combined, for example in a meta-analysis, to help us understand where there may be differences among these groups. The 21st Century Cures Act also included provisions relevant to age. Specifically, it required NIH to convene a workshop on age groupings and age exclusions in clinical research within a 180 days of enactment. And to post workshop findings on a NIH website. It also required that NIH publish data on age of participants in NIH clinical research, including pediatric subgroups. And finally, it required that the NIH director determine whether the inclusion guidelines on age need revision within 180 days of the workshop. So in June 2017, NIH held an Inclusion Across the Lifespan workshop here at the NIH campus in Bethesda, Maryland. And the purpose of that workshop was to discuss challenges and barriers to including children and older adults in clinical research and to identify strategies that would produce more age-inclusive clinical studies. The workshop was attended by over 200 participants, opening remarks were given by Dr. Francis Collins, and there were pediatricians, geriatricians, advocates, researchers, and federal staff, who were all at this meeting to help us understand challenges and barriers relevant to these studies. Following the workshop, and after issuing a request for information on the topic, NIH revised its inclusion of children policy, which is effective for applications submitted for due dates on or after January 25, 2019 and for contract solicitations and intermural studies issues after that date. The new Inclusion Across the Lifespan policy now requires the individuals of all ages be included in NIH human subjects research unless there are scientific or ethical reasons not to do so. So this is different from the inclusion of children policy, which required only that children be included in NIH human subjects research, but now individuals of all ages must be included unless there are reasons for them not to be. The policy also requires submission of individual level data on participant age of enrollment and progress reports. Again, there are cases when including individuals based on age may not be appropriate. And as long as there is a scientific or ethical reason not to include someone, this may be considered to be acceptable. I'd like to talk a bit now about when NIH inclusion policies apply. Inclusion policies apply to all research that's considered to be clinical research. So to determine if inclusion policies apply to your research, you would ask the question, And there is some questions that follow to determine if your study is clinical research. First, you ask, If it does, then you would move on to the next question. If it does not involve human subjects, NIH would not consider it to be clinical research. If your study does involve human subjects, you'd then ask, NIH may or may not consider it to be clinical research. And then the next question you ask is, If your research is considered to be Exemption 4 under the Common Rule, NIH would not consider your study to be clinical research. But all other studies that include human subjects, including studies that involve exempt research, other than Exemption 4, are considered to be clinical research. And thus, the inclusion policies would apply. I want to talk a little bit now about what it means to do inclusive research. What is the purpose of our inclusion policies? And what is NIH looking for in terms of inclusion? And I'd like to remind you that the purpose of the NIH inclusion policies is to make sure that the distribution of study participants by sex or gender, race, ethnicity, and age, reflects the population that's needed to accomplish the scientific goals of the study. We are not trying to issue quotas here. We're not looking simply at the enumeration of research participants, but we really want to know: Does the study have the right people for the science? It's not expected that every study will include every group, but it is expected that the population in your study will allow your results to be generalized to those with the research or condition. So in summary, NIH requires women and minorities be included in all clinical research unless there is a compelling rational for exclusion. An NIH-defined phased III clinical trials must be designed to allow analysis by sex or gender, race, or ethnicity. And finally, following enactment of the 21st Century Cures Act, NIH revised its inclusion of children policy to require individuals of all ages be included in NIH-funded research unless there's a scientific or ethical rational for their exclusion. Now, I'd like to ask you a couple of questions. The first question, true or false: Cost is an acceptable reason to exclude participants from NIH research based on sex or gender? This is false. The law specifically prohibits cost as a reason for excluding participants based on sex or gender. The next question: NIH requires that ever study include at least 50 percent women. True or false? This is false. NIH expects that the population in your study reflect the people needed to answer your scientific question. Again, we're looking at making sure that the right people are in the study for the science. In some cases, that may be 50 percent women, but that's not necessarily the case for every study. I hope you've learned about our NIH inclusion policies today. Thank you very much for listening.