确保临床试验中患者群体多样化的实用策略

Practical S trategies f or E nsuring aDiverse P atient P opulation in Clinical T rials Introduction The clock is ticking on the requirement forpharmaceutical companies to include diversityaction plans (DAPs) for pivotal studies in theirclinical trials. A few deadlines have slippedsince the Food and Drug Omnibus Reform Act(FDORA) was signed into law in April 2022 butthe deadline for comments on the FDA’s draftguidance on DAPs passed on Sept. 26, 2024.The guidance is mandated to be final on June26, 2025, and the act should go into effect 180days later. Citeline experts regard these reformsas necessary and in the industry’s interests formany reasons. Jessica Washington-Moore, Senior Directorof Implementation at Citeline. “If we knowthat these medications are safe and effectivein certain populations, we can provide theright level of care and increase access tounderrepresented communities.” Claire Riches, Head of Clinical Solutions atCiteline, says: “Fundamentally, the long-termbenefit is having data from a real-worldpopulation. Historically, the clinical trialpopulation in the US in pivotal Phase II toIII trials, and indeed globally, was sanitized,skewing towards middle-aged white people withaccess to healthcare and probably a better-than-average prognosis. As a result, studiesoften missed the signals that they would haveseen in a full patient population and outcomessuffered.” “Medications can work differently indifferent populations. If we’re not able totest medications across all races, ethnicities,genders, and ages, then we don’t knowhow they work in these populations,” says Practical S trategies f or E nsuring aDiverse P atient P opulation in Clinical T rials What the FDA wants The stated objective of the act is “toimprove enrollment of participants fromunderrepresented racial and ethnic populationsin clinical trials.” Companies will be requiredto submit enrolment goals disaggregated byethnicity, race, sex, and age group in DAPs, aswell as the rationale for their enrollment goals.These are expected to include: •Considering the accessibility needs ofpersons with disabilities•Using sites that serve a demographicallydiverse population•Study decentralization In addition, the FDA wants to see sponsors’ planto monitor the goals, including any measuresthat may be undertaken should the sponsordetermine that the study is not on track. TheDAP should not be more than 10 pages long,excluding references. It should be submittedwith the protocol for the drug’s pivotal study,which the FDA recommends being at the end-of-Phase-II meeting or whenever the pivotalprotocol is being discussed. The agency has 60days to respond to waiver requests, so thesemust be submitted at least 60 days before DAPsubmission is required and early enough to allowa DAP to be prepared if the request is rejected. •Background information necessaryto understand the disease, includingprevalence and incidence estimates•Data on other population-level or individualcharacteristics that could impact clinicaloutcomes•If multiple studies have different goals, howthis contributes to the overall goal•Available data regarding differences inpharmacokinetics (PK), pharmacodynamics(PD), safety, or effectiveness The FDA has also listed examples of measurescompanies might take to meet their enrollmentgoals. These include, but are not necessarilylimited to: •Sustained community engagement•Cultural competency training for clinicalinvestigators•Language assistance for persons withlimited English proficiency•Transportation assistance•Avoiding unnecessary study-relatedprocedures, imaging, and laboratory tests•Reimbursement for costs incurred•Dependent care•Flexible hours for study participation•Limiting clinical study exclusion criteria Practical S trategies f or E nsuring aDiverse P atient P opulation in Clinical T rials Mistrust & other barriers There are, of course, reasons beyond mereconvenience why clinical trials in the US havehistorically skewed away from minority patients:For one, educated, suburban whites were easierto reach. Some communities have a built-inmistrust of the pharmaceutical industry andprescribing physicians, notably among the Blackpopulation because of historic scandals like theTuskegee Institute’s highly unethical studies,for which the government was still payingcompensation until quite recently. Washington-Moore adds that the challengeis not so much having a certain percentageof every race or ethnicity in a study butensuring that the sample in a clinical trial isrepresentative of the real-world prevalence ofthat particular disease. The FDA guidance focuses initially on race,ethnicity, gender, sex, and age, but the agencywants to look at further social determinantsof health, such as economic and educationalstatus, comorbidities, geographic locations, andaccess to transport. These all have potentialimpacts on patients’ access to drugs andcompliance with medication. Although thislevel of detail is not yet mandatory, Riches iscertain