“The [NIH Inclusion Across the Lifespan] policy, and the review and reporting requirements associated with it, should help ensure that children and older adults are not inappropriately excluded from clinical studies. The policy also has the potential to provide a more robust understanding of the full spectrum of participants recruited into clinical studies.”
Together with my NIH colleagues Drs. Marie Bernard and Janine Clayton, we made this point in a 2018 JAMA opinion piece following the inaugural NIH Inclusion Across the Lifespan workshop. Fast forward, we revisited this issue at the NIH’s Inclusion Across the Lifespan 2 workshop held this past September. You can watch the videocast here. The report covering the event was posted today, and I wanted to share some of my takeaways.
Including appropriate participants in research leads to sound science that informs clinical practice. It also means that study results are more likely to be generalizable across populations. We remain committed to these inclusion principles, including as it comes to persons of different ages. The NIH Inclusion Across the Lifespan policy requires individuals of all ages be included in clinical research studies unless there are scientific or ethical reasons to exclude them. More on the policy can be found at this guide notice, blog post, and podcast.
Much has been learned since the policy went into effect nearly two years ago. Yet, barriers still exist for including children, older adults, and other populations in our supported clinical studies. The second workshop was a great opportunity to examine the state of the science, discuss lessons learned, and share evidence-based practical advice to consider going forward. Conversations flowed around four central themes:
- Inclusion and exclusion criteria
- Study designs and metrics
- Recruitment, enrollment, and retention
- Data analysis and study interpretation
Successful implementation of the Inclusion Across the Lifespan Policy requires a paradigm shift in our thinking around inclusion and exclusion criteria. These criteria should not be considered arbitrary parts of a study. Unnecessary exclusions that limit representativeness and generalizability should be avoided. There was also ample talk about adequately weighing risks of excluding groups—like pregnant women and children —with that of their participation and considering how consent strategies affect participation of groups such as sexual minority youth, non-English speakers, and individuals with disabilities. Along with these ideas, several other strategies raised worth noting were:
- Ensure research questions and outcomes reflect community needs and priorities
- Increase access to clinical trials by minimizing participant burden and considering the limitations of participants and caregivers
- Consider the diversity of individuals within a given age group (e.g. size, comorbidities, diet, cognitive status)
- Regularly assess recruitment and retention and make modifications as needed
- Provide training and resources to researchers
Dr. Francis Collins, the NIH Director, underscored there is no clearer case study to demonstrate the importance of inclusion than our current situation. That said, inclusion of persons across all ages remains a persistent challenge for COVID-19 studies. Even though children and older adults will likely be priority populations for approved interventions, the median age of participants in COVID vaccine trials was 33 to 43 years of age. We expect this range to broaden as children are eligible for participation in future vaccine trials.
Echoing a point made during the workshop, we should remember that solely extending the age of eligibility is insufficient to make the study population truly representative. Panelists further underscored participants in COVID-19 trials should represent those at highest risk and those most likely to receive the intervention. Along with all of this, studies must recognize that social factors, from employment to socioeconomic status, may also influence access to trials by these groups.
Where do we go from here? The conversations will go on, alongside evaluating implementation of the Inclusion Across the Lifespan Policy. NIH will continue engaging researchers, patients, their advocates, journals, and industry to address barriers to inclusion of participants in our supported clinical research. Additionally, now that recipients must report individual-level, de-identified age data, this information will further help us measure our progress towards meeting our inclusion goals and appropriately refine next steps.