Improving Public Health Requires Inclusion of Underrepresented Populations in Research

Abstract

Advances in genomics have ushered in promising therapies tailored to the individual. Personalized medicine is promoted and has begun to positively influence care. For example, medications such as trastuzumab for the 30% of breast cancers that overexpress ERBB2 and vemurafenib for patients with late-stage melanoma who carry the V600E variant have been beneficial. 1 Despite these advances, for many sectors of the populationchildren, older adults, pregnant and lactating women, and individuals with physical and intellectual disabilitieslimited evidence-based therapies optimized to their specific medical needs exist. Combined, these groups comprise as much as 58% of the US population (eTable in the Supplement). Research focusing on or at the very least includes members of these groups is critically needed.Until the initial passage of the Best Pharmaceuticals for Children Act in 2002, pediatric drug doses were based on extrapolation from adults. Importantly, body composition and metabolic processes change as children develop, resulting in different safety and efficacy profiles. 2 Similarly, medication needs change with age and with life events. Older patients often have a range of comorbidities and declining organ function that affect drug dosing and effectiveness. Physiological changes during pregnancy not only alter metabolism but include slowing of intestinal transport, doubling of blood volume, increasing renal excretion, and changing of circulating binding proteins. These processes alter pharmacodynamics and effectiveness. Without optimal levels, pregnant women and their fetuses may be exposed to a medication at a nontherapeutic or subtherapeutic dose. For example, a pharmacokinetic study of amoxicillin treatment for anthrax exposure during pregnancy found that the required concentrations were not achievable using the recommended dosing. 3 For individuals with intellectual disabilities, pharmacokineticstudiesrarelyaddressalternativedeliveryroutes, such as gastrostomy tubes or rectal suppositories. Children with Down syndrome who develop acute leukemia have a higher incidence of treatment-related toxic effects from certain chemotherapeutic drugs. Populations affected by physical disabilities have little data available to inform pharmacological care. In a systematic review, individuals with spinal cord injuries demonstrated significantvariationindrugmetabolism,half-life,andclearance. 4 In addition, people with intellectual or physical disabilities often require additional time needed for consent and follow-up, and the uncertainty regarding their comprehension. This likely affects their inclusion in clinical trials. In one analysis, only 2% of 300 clinical trials included people with intellectual disabilities, yet with only minor accommodations, at least 70% of these trials could have included them. 5 In the same populations, however, medi-VIEWPOINT

Medically Tailored Meal Delivery for Diabetes Patients with Food Insecurity: a Randomized Cross-over Trial

“…These include the enrollment of a racial/ ethnically diverse and socioeconomically vulnerable sample who are often left out of studies of diabetes interventions. 32 Follow-up for the primary outcome was excellent, and the randomized design and detailed in-person assessments enhance the internal validity of the findings. Overall, the study population was representative of the primary care population from which it was drawn.…”

Exclusion of Pregnant Women from Clinical Trials during the Coronavirus Disease 2019 Pandemic: A Review of International Registries

“…Inclusion will allow women to make autonomous and evidence-based decisions, which ultimately protects this scientifically complex (not "vulnerable") population through research rather than from it. 21 Pregnant women should be given the opportunity to be included in COVID-19 clinical trials based on the universal concepts of justice, equity, autonomy, and informed consent. We call upon professional organizations both in the United States and worldwide to continue to advocate for the timely inclusion of pregnant women in appropriate trials.…”

Rivaroxaban Precision Dosing Strategy for Real‐World Atrial Fibrillation Patients

“…The real-world patient population is often much more diverse than in the sample studied in the phase III trials, which can result in efficacy, safety, and dosing gaps between these trials and real-world patients. 1,2 This is a particularly concerning problem for drugs in which either under-or overdosing could result in death or severe morbidity. 3,4 We believe that the relatively new direct-acting oral anticoagulants (DOACs; dabigatran, rivaroxaban, apixaban, edoxaban) used to prevent stroke in patients with atrial fibrillation (AF) represent an opportunity to improve efficacy (by reducing stroke incidence) and safety (by reducing incidence and severity of major bleeding episodes) by more precise dosing than is currently available.…”