Got­tlieb lays out re­al world ev­i­dence pri­or­i­ties for 2019 with an eye on dig­i­tal tools

Stress­ing the need for speed and ef­fi­cien­cy, FDA Com­mis­sion­er Scott Got­tlieb on Mon­day of­fered a look at FDA’s plans around re­al-world da­ta (RWD) and re­al-world ev­i­dence (RWE) in 2019.

The speech at the Bi­par­ti­san Pol­i­cy Cen­ter built off a frame­work, re­leased in De­cem­ber, that sought to be­gin the con­ver­sa­tion on how RWD and RWE can sup­port changes to la­bel­ing, in­clud­ing adding or mod­i­fy­ing an in­di­ca­tion, changes in dose, dose reg­i­men or route of ad­min­is­tra­tion; chang­ing or adding new pop­u­la­tions; or the ad­di­tion of com­par­a­tive ef­fec­tive­ness or safe­ty in­for­ma­tion.

“Tra­di­tion­al post­mar­ket stud­ies typ­i­cal­ly re­quire years to de­sign and com­plete and cost mil­lions of dol­lars. By us­ing RWD and RWE, we may be able to pro­vide pa­tients and providers with im­por­tant an­swers much soon­er – iden­ti­fy­ing a broad­er range of safe­ty sig­nals more quick­ly, and fol­low­ing up on them much more ef­fec­tive­ly,” Got­tlieb said, not­ing this is es­pe­cial­ly im­por­tant for treat­ments for un­com­mon con­di­tions, such as rare tu­mor types.

Got­tlieb al­so laid out four ad­di­tion­al ac­tiv­i­ties the FDA is tak­ing in con­nec­tion to RWE and RWD this year.

First, to sup­port the in­te­gra­tion of dig­i­tal tech­nolo­gies in clin­i­cal tri­als, the FDA is plan­ning to con­vene a stake­hold­er meet­ing to help de­vel­op a frame­work on how dig­i­tal sys­tems can be used to en­hance the over­sight of clin­i­cal tri­als.

“To take one ex­am­ple, re­mote- and risk-based mon­i­tor­ing can pro­vide bet­ter reg­u­la­to­ry over­sight,” he said. “These ap­proach­es may low­er de­vel­op­ment costs, and en­able more tri­al sites to an­swer im­por­tant sci­en­tif­ic and clin­i­cal ques­tions as a way to im­prove pa­tient care.”

He al­so said the FDA will use dig­i­tal tech­nolo­gies to bring clin­i­cal tri­als to the pa­tient, rather than al­ways re­quir­ing the pa­tient to trav­el to the in­ves­ti­ga­tor.

“To sup­port the de­vel­op­ment and adop­tion of de­cen­tral­ized tri­als, the FDA es­tab­lished a for­mal work­ing group on de­cen­tral­ized tri­als, and we’re work­ing to­wards writ­ing a guid­ance doc­u­ment to out­line our ap­proach. We’ll
have much more to say about this in the next month,” he said.

And third, the FDA is ex­plor­ing how re­view­ers can gain more in­sight in­to how la­bel­ing changes in­form provider pre­scrib­ing de­ci­sions and pa­tient out­comes. The FDA’s In­for­ma­tion Ex­change and Da­ta Trans­for­ma­tion (IN­FORMED) is us­ing RWD to ex­am­ine the im­pact of a re­cent FDA la­bel­ing change for two ap­proved prod­ucts from weight-based dos­ing to flat-dos­ing of im­mune check­point in­hibitors.

In 2019, IN­FORMED is go­ing to be work­ing with FDA’s med­ical prod­uct cen­ters to de­vel­op an FDA cur­ricu­lum on ma­chine learn­ing and ar­ti­fi­cial in­tel­li­gence in part­ner­ship with ex­ter­nal aca­d­e­m­ic part­ners.

“The agency will al­so pi­lot a com­pet­i­tive fel­low­ship pro­gram un­der IN­FORMED in ar­ti­fi­cial in­tel­li­gence and ma­chine learn­ing that al­lows post-doc­tor­al fel­lows from lead­ing aca­d­e­m­ic cen­ters to join the FDA for two-year fel­low­ships to de­vel­op high-im­pact AI-based reg­u­la­to­ry sci­ence tools by work­ing close­ly with men­tors from the agency’s med­ical prod­uct cen­ters,” Got­tlieb said.

He al­so not­ed that in on­col­o­gy, the FDA cur­rent­ly has new drug ap­pli­ca­tions un­der re­view where RWD and RWE are help­ing to in­form on­go­ing eval­u­a­tions.

The FDA’s On­col­o­gy Cen­ter of Ex­cel­lence (OCE) is work­ing with Friends of Can­cer Re­search, the Na­tion­al Can­cer In­sti­tute and oth­er stake­hold­ers to har­mo­nize ref­er­ence stan­dards for as­sess­ing tu­mor mu­ta­tion­al bur­den to help iden­ti­fy can­cer pa­tients who are more like­ly to re­spond to im­munother­a­py.

“OCE is al­so work­ing on a project ex­plor­ing whether it’s pos­si­ble to use re­al world end­points, like time to treat­ment dis­con­tin­u­a­tion (TTD) from in lega­cy datasets as a po­ten­tial re­al-world end­point for prag­mat­ic ran­dom­ized clin­i­cal tri­als for FDA-ap­proved ther­a­pies in the off-la­bel set­ting, and whether syn­thet­ic con­trol arms based on pri­or clin­i­cal tri­als can be used for tu­mor types where the stan­dard of care has not changed in decades, and the prog­no­sis is es­pe­cial­ly poor,” he added.


Scott Got­tlieb at a 2016 event. BI­PAR­TI­SAN POL­I­CY CEN­TER

First pub­lished here. Reg­u­la­to­ry Fo­cus is the flag­ship on­line pub­li­ca­tion of the Reg­u­la­to­ry Af­fairs Pro­fes­sion­als So­ci­ety (RAPS), the largest glob­al or­ga­ni­za­tion of and for those in­volved with the reg­u­la­tion of health­care and re­lat­ed prod­ucts, in­clud­ing med­ical de­vices, phar­ma­ceu­ti­cals, bi­o­log­ics and nu­tri­tion­al prod­ucts. Email news@raps.org for more in­for­ma­tion.

Author

Zachary Brennan

managing editor, RAPS

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Back last summer, Sarepta CEO Doug Ingram told Duchenne MD families and investors that the FDA’s shock rejection of their second Duchenne MD drug golodirsen was due to some concerns regulators raised about the risk of infection and the possibility of kidney toxicity. But when pressed to release the letter for all to see, he declined, according to a report from BioPharmaDive, saying that kind of move “might not look like we’re being as respectful as we’d like to be.”

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