FDA can do more to en­sure di­ver­si­ty in clin­i­cal tri­als, ex­perts say — in­clud­ing some con­struc­tive bad­ger­ing

The Covid-19 vac­cine and ther­a­peu­tic de­vel­op­ment races have opened many eyes to the re­al­i­ty that clin­i­cal tri­als in the US rarely in­clude the ap­pro­pri­ate num­bers of eth­nic and racial mi­nori­ties. And even when they some­times get close, as with Mod­er­na’s vac­cine, the tri­al had to be de­lib­er­ate­ly slowed to re­cruit ad­di­tion­al Black and His­pan­ic par­tic­i­pants.

Ex­perts con­vened on Mon­day as part of a work­shop at the Na­tion­al Acad­e­mies of Sci­ences, En­gi­neer­ing, and Med­i­cine, and dis­cussed whether the FDA might take a more promi­nent role in ad­vo­cat­ing for more di­ver­si­ty, among oth­er top­ics to in­form the on­go­ing work of the Na­tion­al Acad­e­mies Com­mit­tee on Im­prov­ing the Rep­re­sen­ta­tion of Women and Un­der­rep­re­sent­ed Mi­nori­ties in Clin­i­cal Tri­als and Re­search.

“The FDA has an un­rec­og­nized abil­i­ty to bad­ger spon­sors along the way,” said for­mer FDA com­mis­sion­er Rob Califf, who now works as an ad­vi­sor to Google’s Ver­i­ly Life Sci­ences. The FDA re­view teams al­so can check in on the da­ta around the rep­re­sen­ta­tive pop­u­la­tions and put ad­di­tion­al pres­sure on the spon­sor, he added.

The agency pub­lished fi­nal guid­ance on clin­i­cal tri­al di­ver­si­ty last No­vem­ber, not­ing the ex­tent of chal­lenges for cer­tain groups who con­tin­ue to be un­der­rep­re­sent­ed in many tri­als. But the guid­ance does not add any new re­quire­ments on en­sur­ing di­verse pop­u­la­tions are en­rolled in stud­ies.

Rob Califf

And it’s not just FDA. Califf said he’s push­ing for a wider glob­al dis­cus­sion on how reg­u­la­tors can ad­dress di­ver­si­ty, not­ing that the pub­lic ag­gre­ga­tion of in­for­ma­tion has to be done in ways that peo­ple can uni­ver­sal­ly un­der­stand. There al­so needs to be a bet­ter sys­tem for track­ing post­mar­ket da­ta and un­der­stand­ing how cer­tain drugs af­fect cer­tain pop­u­la­tions and sub­pop­u­la­tions.

“The gap be­tween when a drug is ap­proved and un­der­stand­ing how it should be used and how it af­fects sub­pop­u­la­tions is just a gap­ing hole,” Califf said. “It can’t just be US on­ly.”

Mar­sha Hen­der­son, the FDA’s for­mer as­so­ciate com­mis­sion­er for women’s health, al­so ex­plained the im­por­tance of ad­vo­ca­cy in push­ing for di­ver­si­ty, not­ing that one of the on­ly rea­sons an in­creas­ing num­ber of women are now en­rolled in clin­i­cal tri­als is be­cause there was a con­sis­tent voice.

“FDA is no­to­ri­ous for not fol­low­ing up on cer­tain is­sues be­cause their re­sources are tilt­ed to­ward user fees,” Hen­der­son said. “I think it’s time for more sur­veil­lance.”

The re­cent ex­am­ple of Mod­er­na slow­ing its Covid-19 vac­cine tri­al for sev­er­al weeks last Sep­tem­ber and Oc­to­ber to al­low for more non-white par­tic­i­pants did lit­tle to shift the over­all tri­al, which end­ed up with more than 60% white par­tic­i­pants.

Melanie Ivars­son

Melanie Ivars­son, chief de­vel­op­ment of­fi­cer at Mod­er­na, ac­knowl­edged to the work­shop, with re­spect to her com­pa­ny’s racial and eth­nic de­mo­graph­ics in the vac­cine tri­al: “Was it good enough? No. Could we have done bet­ter? Yes.”

She said the de­ci­sion to stop en­rolling white peo­ple for those few weeks came as “a big shock for the sites” as they were al­so run­ning an­oth­er vac­cine tri­al for Pfiz­er, and they were prepar­ing for tri­als from As­traZeneca and J&J, and “want­ed to move along,” she said. “It’s not just in­dus­try who will solve this prob­lem.”

Com­pa­nies al­so don’t nec­es­sar­i­ly have to slow their clin­i­cal de­vel­op­ment pro­grams to reach more di­verse pop­u­la­tions.

Melis­sa Gon­za­les

Melis­sa Gon­za­les, in­clu­sion prin­ci­pal at Roche’s Genen­tech, ex­plained to the work­shop how, “If you go to the right sites, it’s not re­al­ly a slow­down. Go to where the pa­tients are ac­tu­al­ly seek­ing care, which takes some time to look in­to the clin­i­cal tri­al in­fra­struc­ture. Do the work up­front and en­gage the com­mu­ni­ty pop­u­la­tions … You can’t just show up in the com­mu­ni­ties when there’s a tri­al they need.”

The com­ments fol­low sim­i­lar sen­ti­ments ex­pressed by FDA act­ing com­mis­sion­er Janet Wood­cock and NIH di­rec­tor Fran­cis Collins. “The way in which bio­med­ical re­search works is con­t­a­m­i­nat­ed by struc­tur­al racism,” Collins said.

Califf added on Mon­day, “If you want to look at struc­tur­al racism, go two coun­ties away from any big aca­d­e­m­ic med­ical cen­ter and ask about ac­cess to clin­i­cal care … tri­als in the US are way ahead of clin­i­cal prac­tice.”

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