As the FDA crafts a new se­ries of guid­ance doc­u­ments on how bio­phar­ma com­pa­nies can use re­al-world da­ta, in­clud­ing pa­tient reg­istries, to help sup­ple­ment their ap­pli­ca­tions, phar­ma com­pa­nies and in­dus­try group PhRMA are call­ing for more de­tails and more con­sis­ten­cy from the agency.

The push from in­dus­try around the use of re­al-world da­ta has been sup­port­ed by both the 21st Cen­tu­ry Cures Act and in­dus­try-ne­go­ti­at­ed PDU­FA VI (the next it­er­a­tion of which is com­ing soon).

In­dus­try group PhRMA ex­plained in a com­ment post­ed last week that com­mon el­e­ments from these co­or­di­nat­ed RWD guid­ance doc­u­ments from FDA “are not al­ways aligned with the rec­om­men­da­tions in this [reg­istry] guid­ance, which may cause con­fu­sion. Sim­i­lar ap­proach­es should be ap­plic­a­ble across many RWD sources and the guid­ances should be aligned ac­cord­ing­ly.”

Re­leased in No­vem­ber, the draft guid­ance is in­tend­ed to help spon­sors and FDA with con­sid­er­a­tions when ei­ther propos­ing to de­sign a reg­istry or us­ing an ex­ist­ing reg­istry to sup­port reg­u­la­to­ry de­ci­sion-mak­ing about a drug’s ef­fec­tive­ness or safe­ty.

“In gen­er­al, reg­istries are bet­ter suit­ed as a da­ta source for reg­u­la­to­ry pur­pos­es when spon­sors aim to cap­ture ob­jec­tive end­points,” the FDA says in the draft, “such as death or hos­pi­tal­iza­tion. Sub­jec­tive end­points, such as pain, can be col­lect­ed in a reg­istry, but ad­di­tion­al chal­lenges are in­volved to stan­dard­ize such mea­sure­ments.”

In­com­ing FDA chief Rob Califf has been a fan of RWD, par­tic­u­lar­ly when ran­dom­ized, and has worked on the top­ic in his pre­vi­ous role at Google’s par­ent com­pa­ny Al­pha­bet. Life sci­ence com­pa­nies, which pre­vi­ous­ly sought more de­tails on pri­or guid­ance docs, are again call­ing on the FDA to ex­plain it­self more.

Na­jat Khan

McKesson, which op­er­ates an on­col­o­gy re­al-world da­ta and ev­i­dence busi­ness called On­ta­da, wrote, “At a min­i­mum, FDA guid­ance should in­clude con­tent around the com­mon types of reg­istries (i.e., pa­tient, spe­cial­ty, provider, de­vice, and pop­u­la­tion-lev­el), and specif­i­cal­ly, their unique char­ac­ter­is­tics should in­clude spe­cif­ic da­ta el­e­ments that make a reg­istry ‘fit-for pur­pose’ for a par­tic­u­lar sci­en­tif­ic ob­jec­tive or use case.”

J&J’s Janssen al­so wants the FDA to go fur­ther in ex­plain­ing how reg­istries might fac­tor in­to the agency’s ben­e­fit-risk as­sess­ments for new drugs:

For ex­am­ple, safe­ty and ef­fi­ca­cy end­points de­rived from reg­istry da­ta can be de­signed with the same breadth and de­tail as those used in the con­text of a ran­dom­ized con­trolled clin­i­cal tri­al. Reg­istry end­points have the ad­van­tage over some oth­er types of da­ta sources as du­pli­ca­tions are more eas­i­ly iden­ti­fied and ad­dressed, and the study time­frames and units cap­tured can be uni­form. Reg­istries al­so have the po­ten­tial to mea­sure sever­i­ty of dis­ease, not just dis­ease oc­cur­rence and can al­low the eval­u­a­tion of ben­e­fits and risks in the re­al-world set­ting. To this end, Janssen re­quests that as the Draft Guid­ance is fi­nal­ized, FDA in­clude dis­cus­sion on how reg­istry da­ta may in­form the ben­e­fit-risk as­sess­ment.

Janssen’s chief da­ta sci­ence of­fi­cer Na­jat Khan wrote that the draft guid­ance “would be sig­nif­i­cant­ly strength­ened if the FDA in­clud­ed dis­cus­sion of chal­lenges and po­ten­tial so­lu­tions as well as ad­van­tages and lim­i­ta­tions of sec­ondary use of reg­istry da­ta.”

Mark Taisey

Am­gen’s VP Bri­an Brad­bury and SVP Mark Taisey called on the FDA to in­clude a few ex­am­ples of reg­istries used for reg­u­la­to­ry de­ci­sion-mak­ing, in­clud­ing the use of an ex­ist­ing reg­istry and the de­sign of a new reg­istry.

They al­so of­fer its own ex­am­ple of the Nordic Coun­try Pa­tient Reg­istry for Romi­plostim, which was orig­i­nal­ly es­tab­lished in 2009 as a post-au­tho­riza­tion safe­ty study to as­sess the long-term safe­ty and out­comes in adult pa­tients with chron­ic im­mune throm­bo­cy­tope­nia and was used to con­duct a study of com­par­a­tive ef­fec­tive­ness of romi­plostim ver­sus SOC with the goal of sup­port­ing an ex­pan­sion of the romi­plostim la­bel.

Bri­an Brad­bury

“Ad­di­tion­al­ly, the EX­PECT preg­nan­cy reg­istry ex­am­ined the oc­cur­rence of ma­jor con­gen­i­tal anom­alies in preg­nant women with se­vere asth­ma treat­ed with oma­l­izum­ab,” Brad­bury and Taisey wrote.

Boehringer In­gel­heim sim­i­lar­ly calls for ex­am­ples of use of re­al-world ev­i­dence, “specif­i­cal­ly reg­istries to sup­port the ap­proval of a new in­di­ca­tion.” Boehringer of­fers the ex­am­ple of use of reg­istry da­ta from the US Sci­en­tif­ic Reg­istry of Trans­plant Re­cip­i­ents for an ap­proval of a new in­di­ca­tion of tacrolimus.

Am­gen al­so calls on the FDA to ex­pand its de­f­i­n­i­tion of RWE in this guid­ance and oth­ers, to in­clude (ad­di­tion in bold), “RWE is the clin­i­cal ev­i­dence about the us­age and the po­ten­tial ben­e­fits or risks of a med­ical prod­uct or about a dis­ease state de­rived from analy­sis of RWD.”

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AbbVie is approaching the FDA with a new therapy to potentially treat Parkinson’s disease, using prodrugs of two medications commonly used for the condition.

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