On­col­o­gy re­search mid-pan­dem­ic: Chal­lenges may bring durable in­no­va­tion

Though clin­i­cal re­search, in gen­er­al, has been chal­lenged dur­ing the COVID-19 pan­dem­ic, on­col­o­gy tri­als “have sev­er­al unique con­sid­er­a­tions due to dis­ease sever­i­ty, reg­i­men com­plex­i­ty, and acute care re­quire­ments” that have caused even greater chal­lenges, US FDA of­fi­cials wrote in a new view­point pub­lished in JA­MA On­col­o­gy.

Da­ta in­tegri­ty is­sues and “pan­dem­ic-in­duced pro­to­col de­vi­a­tions” are a con­cern for spon­sors and FDA alike, and the agency has been at­tempt­ing to be as flex­i­ble as is pos­si­ble while safe­guard­ing pa­tient well­be­ing and clin­i­cal tri­al in­tegri­ty, ac­cord­ing to Anand Shah, FDA deputy com­mis­sion­er for med­ical and sci­en­tif­ic af­fairs, Richard Paz­dur, di­rec­tor of the FDA On­col­o­gy Cen­ter of Ex­cel­lence (OCE), and Kushal Kada­ka, health sci­en­tist in the of­fice of the com­mis­sion­er. Tele­health for pa­tient mon­i­tor­ing has bur­geoned dur­ing the pan­dem­ic, for ex­am­ple, an ap­proach that min­i­mizes dis­ease ex­po­sure for vul­ner­a­ble tri­al par­tic­i­pants while al­low­ing da­ta col­lec­tion to con­tin­ue.

Still, “not all end­points may be con­ducive to vir­tu­al as­sess­ment,” ac­knowl­edged the FDA of­fi­cials, ad­vis­ing spon­sors to seek ad­vice from FDA on how best to pro­ceed when med­ical imag­ing and blood­work are re­quired in a ge­o­graph­ic area with high coro­n­avirus ac­tiv­i­ty.

Look­ing specif­i­cal­ly at on­col­o­gy tri­als, the au­thors point­ed out that some pa­tients with ad­vanced dis­ease “may re­ly on tri­al en­roll­ment to ac­cess in­ves­ti­ga­tion­al drugs to treat their con­di­tion.”

FDA has been keep­ing up with its on­col­o­gy ap­provals work­load dur­ing the pan­dem­ic: be­tween March and May 2020, OCE has ap­proved eight new mol­e­c­u­lar en­ti­ties and 23 new on­col­o­gy in­di­ca­tions, the au­thors wrote.

Look­ing for­ward, there may be lessons for in­no­va­tion in on­col­o­gy re­search. “The FDA in­tends to re­view all the tem­po­rary poli­cies is­sued dur­ing the pan­dem­ic to iden­ti­fy which reg­u­la­to­ry flex­i­bil­i­ties, if ap­pro­pri­ate, should be per­ma­nent­ly in­cor­po­rat­ed in­to agency prac­tice,” the au­thors said, adding that this flex­i­bil­i­ty is in many ways a “nat­ur­al ex­ten­sion” of ef­forts al­ready un­der­way.

In an in­ter­view, a reg­u­la­to­ry af­fairs pro­fes­sion­al con­curs. “In gen­er­al, any op­por­tu­ni­ty to ac­cel­er­ate can­cer drug de­vel­op­ment with­out neg­a­tive­ly im­pact­ing clin­i­cal tri­al in­tegri­ty or da­ta qual­i­ty would be ben­e­fi­cial to all stake­hold­ers, es­pe­cial­ly pa­tients,” said Daniel Man­nix, FRAPS, vice pres­i­dent of reg­u­la­to­ry af­fairs at Macro­Gen­ics.

Man­nix point­ed to the on­go­ing use of re­al-world ev­i­dence (RWE) as an ex­am­ple of the flex­i­bil­i­ty and in­no­va­tion that the FDA is al­ready em­ploy­ing.

“FDA has been a par­tic­i­pant in the RWE pi­lot spon­sored by Friends of Can­cer Re­search to as­sess sev­er­al front­line treat­ment reg­i­mens in re­al-world pa­tients with ad­vanced non-small cell lung can­cer,” Man­nix said. Pfiz­er’s Ibrance ap­proval in 2019 for male breast can­cer was al­so sup­port­ed by RWE, he not­ed. “RWE was a com­po­nent of [Pre­scrip­tion Drug User Fee Amend­ments (PDU­FA)] VI and FDA is look­ing to build up­on this fur­ther in PDU­FA VII.”

The pan­dem­ic is al­ready gen­er­at­ing da­ta on how on­col­o­gy drugs are used out­side of the tra­di­tion­al clin­i­cal tri­al set­ting, and the emer­gency has forced a reap­praisal of how end­points are be­ing as­sessed — speed­ing the adop­tion of pa­tient-cen­tered out­comes, the au­thors wrote.

“The shift­ing of cer­tain as­pects of clin­i­cal tri­al op­er­a­tions to com­mu­ni­ty set­tings to re­duce pa­tient bur­den al­so could sup­port this ac­cel­er­a­tion,” Man­nix said. “In the past, on­col­o­gy clin­i­cal tri­als have uti­lized satel­lite cen­ters af­fil­i­at­ed with a pri­ma­ry clin­i­cal tri­al site, but there have con­cerns over cer­tain GCP [good clin­i­cal prac­tice] el­e­ments. Re­cent FDA guid­ance doc­u­ments is­sued dur­ing the COVID-19 pan­dem­ic have now ad­dressed how spon­sors should deal with these po­ten­tial GCP is­sues to help en­sure clin­i­cal tri­al in­tegri­ty.”

Fi­nal­ly, the FDA and spon­sors have seen dig­i­tal plat­forms used for pa­tient en­roll­ment as well as da­ta col­lec­tion. Us­ing dig­i­tal en­roll­ment plat­forms as part of a com­mu­ni­ty out­reach strat­e­gy could be a pow­er­ful tool to help in­crease di­ver­si­ty of pa­tient pop­u­la­tions in clin­i­cal tri­als, said the au­thors. Re­tain­ing this strat­e­gy, along with oth­er in­no­va­tions, would rep­re­sent “at least one pos­i­tive out­come of this chal­leng­ing time for pub­lic health,” the au­thors said.

First pub­lished in Reg­u­la­to­ry Fo­cus™ by the Reg­u­la­to­ry Af­fairs Pro­fes­sion­als So­ci­ety, the largest glob­al or­ga­ni­za­tion of and for those in­volved with the reg­u­la­tion of health­care prod­ucts. Click here for more in­for­ma­tion.

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