FDA de­vel­op­ing guid­ance on re­al-world da­ta qual­i­ty is­sues, of­fi­cials say

As the FDA grap­ples with how to use re­al-world da­ta for reg­u­la­to­ry de­ci­sions, two FDA of­fi­cials wrote in a per­spec­tive pub­lished last Fri­day in the Clin­i­cal Jour­nal of the Amer­i­can So­ci­ety of Nephrol­o­gy that the agency is de­vel­op­ing guid­ance on da­ta qual­i­ty is­sues unique to the re­al-world da­ta set­ting and re­lat­ed study de­sign con­sid­er­a­tions.

Al­iza Thomp­son and Mary Ross South­worth of the Di­vi­sion of Car­dio­vas­cu­lar and Re­nal Prod­ucts with­in FDA’s Cen­ter for Drug Eval­u­a­tion and Re­search (CDER) ex­plain: “Al­though the FDA has ex­pe­ri­ence us­ing ob­ser­va­tion­al (non­in­ter­ven­tion­al) study de­signs in the post­mar­ket set­ting to eval­u­ate prod­uct risks in broad pop­u­la­tions, us­ing non­ran­dom­ized method­olo­gies to de­ter­mine ef­fec­tive­ness can be prob­lem­at­ic be­cause of con­cerns about the abil­i­ty to ad­e­quate­ly con­trol for con­found­ing, se­lec­tion bias, and the pos­si­bil­i­ty of mis­clas­si­fi­ca­tion er­ror.”

New da­ta stan­dards will need to be de­vel­oped and the FDA is “cur­rent­ly ex­plor­ing,” they write, when the use of ob­ser­va­tion­al da­ta “may be ap­pro­pri­ate for eval­u­at­ing ef­fec­tive­ness from a broad pol­i­cy per­spec­tive and al­so, as in­di­vid­ual drug man­u­fac­tur­ers sub­mit pro­pos­als for us­ing re­al world da­ta to sup­port mar­ket­ing ap­pli­ca­tions.”

The draft guid­ance in de­vel­op­ment is not on CDER’s 2019 guid­ance agen­da, but the FDA did pub­lish draft guid­ance in May on re­al-world ev­i­dence (RWE) sub­mis­sions. Last De­cem­ber, the agency al­so re­leased its frame­work for the use of RWE.

“There is wide­spread recog­ni­tion that there will be a learn­ing curve and that demon­stra­tion projects will play a crit­i­cal role in defin­ing how and when re­al world da­ta and re­al world ev­i­dence can be used,” Thomp­son and South­worth add.

Kid­ney Dis­ease

They al­so dis­cuss how re­al-world da­ta and RWE could pro­vide a way to ac­cel­er­ate the de­vel­op­ment of ther­a­pies that im­prove the lives of pa­tients with kid­ney dis­ease.

“Many have not­ed the po­ten­tial to in­te­grate RCTs [ran­dom­ized con­trolled tri­als] in­to the da­ta-rich clin­i­cal care set­ting of pa­tients on dial­y­sis, and ef­forts are un­der­way to un­der­stand and ad­dress cur­rent chal­lenges to do­ing so,” they ex­plain. “In RCTs of pa­tients with com­mon kid­ney dis­eases, such as di­a­bet­ic kid­ney dis­ease, re­al world da­ta could be used to fa­cil­i­tate the iden­ti­fi­ca­tion and en­roll­ment of pa­tients in­to tri­als. Study method­olo­gies aimed at cap­tur­ing key ef­fi­ca­cy out­comes us­ing both tra­di­tion­al meth­ods, and elec­tron­ic health records or claims da­ta could pro­vide in­sight in­to the chal­lenges and op­por­tu­ni­ties of us­ing re­al world da­ta to as­sess out­comes of in­ter­est by en­abling a com­par­i­son be­tween the two.”

But they warn that giv­en the “size of the pop­u­la­tion with stage 4 and 5 CKD [chron­ic kid­ney dis­ease] and frag­men­ta­tion of health care among var­i­ous US health care sys­tems, suc­cess­ful use of such da­ta will like­ly re­quire col­lab­o­ra­tion among re­searchers and the ag­gre­ga­tion of re­al world da­ta from mul­ti­ple sources. How­ev­er, these nov­el ap­proach­es should not sup­plant larg­er ef­forts to in­clude these pop­u­la­tions in reg­is­tra­tion tri­als for drugs, where ap­pro­pri­ate, or con­duct ded­i­cat­ed RCTs in these pop­u­la­tions.”

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.


Zachary Brennan

managing editor, RAPS

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