Pa­tient ex­pe­ri­ence da­ta: Sanofi re­searchers call for more con­sis­ten­cy from FDA

Re­searchers at drug­mak­er Sanofi are call­ing on the FDA to make its pub­li­ca­tion of pa­tient ex­pe­ri­ence da­ta (PED) in re­view doc­u­men­ta­tion more con­sis­tent af­ter re­view­ing ap­pli­ca­tions ap­proved in the first full year af­ter a re­quire­ment of the 21st Cen­tu­ry Cures Act com­pelled the agency to do so.

Un­der Sec­tion 3001 of the 21st Cen­tu­ry Cures Act, the FDA is re­quired to “pub­lish a brief state­ment on any pa­tient ex­pe­ri­ence da­ta or re­lat­ed in­for­ma­tion that was part of the ap­pli­ca­tion” for ap­pli­ca­tions sub­mit­ted af­ter 16 June 2017.

In 2018, the FDA’s Cen­ter for Drug Eval­u­a­tion and Re­search (CDER) ap­proved 59 nov­el drugs and bi­o­log­ics. Of those, 48 ap­pli­ca­tions (81.4%) in­clud­ed a Sec. 3001 PED ta­ble with­in the re­view doc­u­men­ta­tion. Among the 11 prod­ucts that did not in­clude a PED ta­ble, sev­en were sub­mit­ted to the FDA pri­or to the im­ple­men­ta­tion date for Sec. 3001.

Among the 48 ap­pli­ca­tions that in­clud­ed a PED ta­ble, the re­searchers found that 34 (70.8%) re­port­ed us­ing PED dur­ing the re­view. Of those 34 ap­pli­ca­tions, 29 (60.4%) in­clud­ed on­ly spon­sor-sub­mit­ted PED, four (8.3%) in­clud­ed spon­sor- and non­spon­sor-sub­mit­ted PED and one (2.1%) in­clud­ed on­ly non­spon­sor-sub­mit­ted PED.

The sources of the non­spon­sor-sub­mit­ted PED in­clud­ed the FDA pa­tient-fo­cused drug de­vel­op­ment meet­ing sum­maries, a meet­ing be­tween the FDA and pa­tient stake­hold­ers and an FDA ad­vi­so­ry com­mit­tee meet­ing.

The re­searchers al­so re­viewed the use of PED across prod­ucts with spe­cial reg­u­la­to­ry des­ig­na­tions, in­clud­ing or­phan drug des­ig­na­tion, break­through ther­a­py des­ig­na­tion, fast track des­ig­na­tion, pri­or­i­ty re­view and ac­cel­er­at­ed ap­proval.

Con­trary to their ex­pec­ta­tions, the re­searchers found that ap­pli­ca­tions with or­phan des­ig­na­tion were less like­ly to in­clude PED in their re­view doc­u­men­ta­tion, with 60.7% of ap­pli­ca­tions with or­phan des­ig­na­tion in­clud­ing PED com­pared to 85% of non-or­phan ap­pli­ca­tions uti­liz­ing PED as part of their re­view.

The re­searchers ob­served a sim­i­lar trend for ap­pli­ca­tions that re­ceived fast track sta­tus or a pri­or­i­ty re­view, not­ing that 61.9% of ap­pli­ca­tions with fast track sta­tus and 64.9% of pri­or­i­ty re­views in­clud­ed PED, while 77.8% of non-fast track and 90.9% non-pri­or­i­ty re­view ap­pli­ca­tions in­clud­ed PED.

On the oth­er hand, prod­ucts grant­ed break­through ther­a­py des­ig­na­tion or ac­cel­er­at­ed ap­proval were more like­ly to in­clude PED in their re­view doc­u­men­ta­tion.

“In­clu­sion of the PED ta­ble with­in the FDA Re­view Doc­u­men­ta­tion—which are by na­ture high­ly tech­ni­cal and ac­cessed pri­mar­i­ly by spon­sors and aca­d­e­mics—would lim­it their vis­i­bil­i­ty to stake­hold­ers less fa­mil­iar with the FDA reg­u­la­to­ry process (such as pa­tient groups and health­care providers),” the re­searchers write.

The re­searchers al­so point out that while the for­mat of the PED ta­bles in­clud­ed in the re­view doc­u­men­ta­tion were “large­ly con­sis­tent through­out these 48 drug prod­uct ap­pli­ca­tions, the use of the ta­ble by FDA re­view­ers var­ied sig­nif­i­cant­ly,” not­ing that in just over half of the ap­pli­ca­tions (58.3%) the PED ta­ble spec­i­fied the ap­pli­ca­tion sec­tion where PED was dis­cussed. Ad­di­tion­al­ly, the re­searchers say that on­ly nine of the 29 ap­pli­ca­tions that in­clud­ed pa­tient re­port­ed out­come (PRO) da­ta spec­i­fied which PRO in­stru­ment was used.

“Fur­ther, it ap­pears that FDA did not con­sis­tent­ly pub­lish a PED ta­ble for sup­ple­men­tal ap­pli­ca­tions, which are al­so ap­proved un­der FD&C Act 505(b) or PH­SA 351(a)—while this in­for­ma­tion some­times can be ac­cessed by oth­er means, there is no con­sol­i­dat­ed, ‘pub­licly avail­able’ ac­cess to this in­for­ma­tion,” the re­searchers write.

The re­searchers high­light the fact that clin­i­cal out­come as­sess­ments (COAs), in­clud­ing PROs, ac­count­ed for near­ly three-quar­ters (73.2%) of the sources of PED in the ap­pli­ca­tions.

While the re­searchers note that this may be due to both spon­sors and the FDA hav­ing more ex­pe­ri­ence with COAs com­pared to oth­er sources of PED. “Based on the re­sults of this re­view, both the FDA and spon­sors should en­sure that all forms of PED, be­yond COAs, are ap­pro­pri­ate­ly be­ing in­cor­po­rat­ed in­to drug de­vel­op­ment,” they write.

Look­ing ahead, the re­searchers say they ex­pect the FDA to be more con­sis­tent in its han­dling of PED across its re­view di­vi­sions and ar­gue that the re­quire­ments un­der Sec­tion 3001 of the Cures Act should ap­ply to sup­ple­men­tal ap­pli­ca­tions as well.

Ad­di­tion­al­ly, the re­searchers say that the FDA could make its use of PED more ac­ces­si­ble by in­clud­ing a plain lan­guage “pa­tient-fac­ing state­ment de­scrib­ing FDA’s use and ap­pli­ca­tion of PED for each ap­proval,” sim­i­lar to how the agency pro­vides its drug tri­al snap­shots.

The re­searchers al­so ar­gue that the FDA should in­clude or link to its use of PED in its re­views of ap­pli­ca­tions in ap­proved la­bel­ing. “With­out di­rect in­clu­sion in la­bel­ing, or at least a mean­ing­ful and ac­ces­si­ble link­age of the in­for­ma­tion to la­bel­ing, true pub­li­ca­tion of FDA’s use of pa­tient in­put ar­guably has not been ef­fec­tu­at­ed for the ben­e­fit of all users,” the re­searchers write.

FDA Re­port­ed Use of Pa­tient Ex­pe­ri­ence Da­ta in 2018 Drug Ap­provals

RAPS: 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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