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

Nick Leschly via Getty

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Blue­bird bio $BLUE has un­veiled its price for the new­ly ap­proved gene ther­a­py Zyn­te­glo (Lenti­Glo­bin), which came as a big sur­prise. And it wasn’t the on­ly un­ex­pect­ed twist in to­day’s sto­ry.

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Gene ther­a­pies seize the top of the list of the most ex­pen­sive drugs on the plan­et — and that trend has just be­gun

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News­mak­ers at #EHA19: Re­gen­eron, Ar­Qule track progress on re­sponse rates

Re­gen­eron’s close­ly-watched bis­pe­cif­ic con­tin­ues to ring up high re­sponse rates

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A to­tal of 13 out of 14 fol­lic­u­lar lym­phomas re­spond­ed to the drug, a 93% ORR, down from 100% at the last read­out. In 10 out of 14, there was a com­plete re­sponse. In dif­fuse large B-cell lym­phoma the re­sponse rate was 57% among pa­tients treat­ed at the 80 mg to 160 mg dose range. They were all com­plete re­spons­es. And 2 of these Cars were for pa­tients who had failed CAR-T ther­a­py.

Neil Woodford, Woodford Investment Management via YouTube

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Po­livy, or po­latuzum­ab ve­dotin, is a first-in-class drug tar­get­ing CD79b — a pro­tein promi­nent in B-cell non-Hodgkin lym­phoma. It will now be mar­ket­ed for dif­fuse large B-cell lym­phoma as part of a reg­i­men that al­so in­cludes the chemother­a­py ben­damus­tine and a ver­sion of rit­ux­imab (Rit­ux­an).

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An in­censed Cat­a­lyst Phar­ma sues the FDA, ac­cus­ing agency of bow­ing to po­lit­i­cal pres­sure and break­ing fed­er­al law

Af­ter hint­ing it was ex­plor­ing the le­gal­i­ty of the FDA’s ap­proval of a ri­val drug from fam­i­ly-run com­pa­ny Ja­cobus Phar­ma­ceu­ti­cals, Cat­a­lyst Phar­ma­ceu­ti­cals on Wednes­day filed a law­suit against the health reg­u­la­tor — ef­fec­tive­ly ac­cus­ing the agency of bow­ing to po­lit­i­cal pres­sure sur­round­ing sky­rock­et­ing drug prices.

Be­fore Cat­a­lyst’s Fir­dapse (which car­ries an av­er­age an­nu­al list price of $375,000) was sanc­tioned for use in Lam­bert-Eaton myas­thenic syn­drome (LEMS) by the FDA, hun­dreds of pa­tients had been able to ac­cess a sim­i­lar drug from com­pound­ing phar­ma­cies for a frac­tion of the cost, or Ja­cobus’ for free, as part of an FDA-rat­i­fied com­pas­sion­ate use pro­gram. But the ap­proval of the Cat­a­lyst drug — ac­com­pa­nied by mar­ket ex­clu­siv­i­ty span­ning sev­en years — ef­fec­tive­ly pre­clud­ed Ja­cobus and com­pound­ing phar­ma­cies from sell­ing their ver­sions.

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