Eligibility and Study Design

This study had three phases (Fig. 1). The first phase was retrospective and focused on the 2 years prior to implementation of the 2019 NIH Lifespan Policy. In order to be eligible for this review, studies had to be initiated by an OHSU investigator (defined as “PI involved in the design of the protocol”), require prospective consent, address a disease or condition relevant to older adults (defined as “individuals 65 + years old”), and be closed to enrollment between January 2017 and December 2018. Studies were screened for eligibility by review of IRB project title, proposed age range, and brief study description. Studies were excluded if they were industry-sponsored (unless the industry involvement was funding only and the study was investigator-initiated); if they were multicenter trials where OHSU was not the coordinating center; or if the disease in question was not relevant to older adults (e.g., maternal/neonatal diseases and pediatric cancers). We reviewed these studies to see if there was a mismatch between inclusion criteria age ranges and the age demographics of the studied disease or research question. Mismatch was determined based on review of the demographics of the disease or condition being studied compared to the demographics of the study as submitted. Demographics of diseases were determined through the use of Centers for Disease Control and Prevention [5], NIH [6], and other organizations that publish this information. We searched databases available from these entities to find the most comprehensive demographic information and then combined this information to create a disease demographic reference sheet (see Supplemental Materials). Each disease or condition was assigned both a disease demographics range (based on the highest and lowest age at which the condition typically occurs) and a prevalence range (based on the ages at which the condition is most prevalent).

Figure 1. Timeline of phases throught this study. Red vertical line indicates the start of the NIH Lifespan Policy in January 2019. Phase 1 was the 2-year lookback period assessing protocol age and enrollment age against disease demographics and disease prevalence range. Phase 2 was a 2-year prospective period assessing protocol age against disease demographics and disease prevalence range. Phase 3 was a 3-year prospective period assessing enrollment age against disease demographics and disease prevalence range.

The second phase of the study was prospective and evaluated all new submissions to the IRB for the 2 years following implementation of the NIH Lifespan Policy (dates 1/1/2019–12/31/2020) to compare the disease demographics to the protocol age criteria of studies. Eligibility included new studies submitted to the IRB that were PI-initiated, PI had control over the protocol (e.g., if Multi-site Clinical Trial were the Coordinating Center/Data Coordinating Center), disease-focused, diseases relevant to older adults, and that were submitted to the IRB after 1/1/2019 and prior to 12/31/2020. Interventions in this phase included reaching out to the PI if there was a “mismatch” between disease age range and protocol age range to discuss the rationale for their age range and offer support for adjusting their age range if appropriate. These meetings were conducted by one of the study authors (EE) and followed the protocol: (1) investigator was questioned to learn details of their research study (that could not be gleaned from the IRB proposal); (2) study author reviewed disease demographics with investigator and compared demographics to the IRB protocol age range; (3) study author asked if the investigator would like to expand their age range and offered suggestions for how to do that, including using electronic health record cohort discovery tools, local registries the investigator wasn’t aware of, and suggestions to adapt the protocol to be more feasible and accessible for older adults.

The third phase of this study was prospective monitoring of enrollment of new studies for 3 years after the NIH Lifespan Policy (dates 1/1/2019–12/31/2021) to compare the disease demographics to the enrollment age ranges of studies. Intervention in this phase included reaching out to the PI if there was a “mismatch” between disease age range and enrollment age range to provide tips for recruitment and retention of older adults. The reach out at this phase of the study was similar to the reach out in Phase 2, with added emphasis on retention of older adults.

Data Collection and Analysis

OHSU IRB approval (#STUDY00018894) was received prior to collection of this data. A waiver of documentation of informed consent was approved for this study as the record review posed no more than minimal risk to individuals, appropriate subject privacy protection procedures were in place, and there was no interaction or intervention with the study participants. No sample size calculation was performed because all eligible studies were included.

Data to assess study eligibility were collected using OHSU’s clinical trial management system (“eCRIS”) and IRB records. Study-level information, including disease or condition being studied and inclusion and exclusion criteria, was collected for studies meeting eligibility criteria. Each study was summarized by the targeted disease and proposed minimum and maximum participant ages (referred to as protocol age range). Of note, the protocol age range was determined prior to study enrollment. Participant information – age, race, ethnicity, and gender – was used to summarize the number of total subjects, average participant age, minimum age, maximum age, and age distribution (in the form of a histogram). All study-level and participant-level data were maintained in a REDCap database.

For Phase 1, disease demographics and study data were reviewed and analyzed to determine the level of disease to population “match” or “mismatch.” Participant histograms were charted alongside the protocol minimum and maximum ages, disease demographics range, and prevalence range (Fig. 2) and could be used with research teams to show them how their study age ranges compared with disease age ranges. These charts were reviewed alongside study summaries by the lead author (EE) and scored on each of the following four criteria: (1) how well the protocol age range (as determined by the study team prior to submission to the IRB) matched the disease demographics range (defined as the highest and lowest age at which the condition typically occurs); (2) how well the protocol age range matched the disease prevalence range (defined as the most common ages at which the disease occurs); (3) how well the enrolled subject ages matched the disease demographics range; and (4) how well the enrolled subject ages matched the disease prevalence range. Studies that were a full match (i.e., age ranges matched completely) received two points. Those that were a partial match (i.e., age ranges overlapped but had some mismatch) received one point. Those that were a mismatch (i.e., age ranges mostly did not match) received 0 points. The scoring matrix for each criteria is shown in Table 1. We counted the number and percent of studies with discrepancies and determined which proposals were noncompliant with the NIH Lifespan Policy. We specifically determined if enrolled participants in OHSU studies (a) matched the demographics of the disease in question, (b) fell within the proposed age range for recruitment, and (c) were appropriately distributed across the proposed and/or adjusted age range (as mandated by the NIH Lifespan Policy).

Figure 2. Histogram examples displaying the overlap of enrollment age against disease demographic range and disease prevalence range for a mismatch ( a ) and match ( b ). Disease demographics range, shown in light gray, is the highest and lowest age at which the condition typically occurs. Disease prevalence range, shown in dark gray, is the ages at which the condition is most prevalent.

Table 1. Scoring matrix used to evaluate matching between protocol age and enrollment age to disease demographics and disease prevalence range

For Phase 2 of the study, all eligible new IRB submissions starting in January 2019 (when the NIH Lifespan Policy was implemented) were reviewed in 6-month blocks, and eligible age ranges were determined to be compliant or noncompliant with the policy. Studies in this phase were assessed on the first two criteria listed above related to protocol age: (1) how well the protocol age range matched the disease demographics range and (2) how well the protocol age range matched the disease prevalence range. Studies that were a full match for the two criteria were totaled separately, and the percentage was calculated for both. If a study was deemed to be noncompliant with the policy, our research team reached out to the PI of the study to request a meeting. In that meeting, the PI was asked their rationale for the choice of age range for their study, potential concerns about raising the upper age limit for inclusion in the study, and exploration of needed resources to expand the age inclusion. The PI was encouraged to expand their age range and offered resources to do so. Assistance included providing language for an IRB modification to expand the age of inclusion as appropriate and an offer of follow-up during study recruitment and retention to assist the study team in meeting the expanded age range of participants, among others. All qualitative information collected during these meetings was entered into the REDCap database and used for descriptive analysis. We identified the number of mismatched studies, the number of PIs accepting a meeting, and the number of studies that changed their protocol age range. The number of studies matching on protocol age from Phase 2 was compared to the number of studies matching on protocol age from Phase 1 to both disease demographics and disease prevalence using a proportion test.

Data collection for Phase 3 was similar to that of Phase 2 but focused on enrollment age. Studies in this phase were assessed on the last two criteria listed above: (3) how well the enrolled subject ages matched the disease demographics range and (4) how well the enrolled subject ages matched the disease prevalence. The number of studies that were a full match for each criterion were totaled separately, and the percentage was calculated for both. Study enrollment was reviewed every 6 months for eligible IRB studies, and our study team reached out to PIs whose study enrollment did not mirror demographics of the disease, offering support for inclusion enhancement and documenting responses. All qualitative information collected during these meetings was entered into the REDCap database and used for descriptive analysis. The number of mismatched studies, the number of PIs accepting a meeting, and the number of studies that changed their enrollment age were calculated. The number of studies matching on enrollment age from Phase 3 was compared to the number of studies matching on enrollment age from Phase 1 to both disease demographics and disease prevalence using a proportion test. R version 4.1.3 (R Foundation for Statistical Computing, Vienna, Austria) was used for all statistical analyses.