On­ly about half of a se­lect group of clin­i­cal tri­als could be well-em­u­lat­ed with avail­able re­al world ev­i­dence, ac­cord­ing to the new­ly dis­cussed re­sults of an FDA pi­lot pro­gram.

The FDA-fund­ed pro­gram, known as RCT-DU­PLI­CATE, helped re­searchers from the Brigham and Women’s Hos­pi­tal in Boston try to eval­u­ate whether ran­dom­ized con­trolled tri­als can be du­pli­cat­ed with RWE across a range of ther­a­peu­tic ar­eas.

The ini­tia­tive is part of the FDA’s work, man­dat­ed by Con­gress in the 21st Cen­tu­ry Cures Act, on how it plans to eval­u­ate the use of RWE to as­sess the ef­fec­tive­ness of med­ical prod­ucts.

John Con­ca­to, as­so­ciate di­rec­tor for RWE an­a­lyt­ics in the FDA’s Of­fice of Med­ical Pol­i­cy, made clear at a Duke-Mar­go­lis event on the top­ic last week that the stan­dard for sub­stan­tial ev­i­dence re­mains un­changed. He al­so not­ed that seek­ing to em­u­late a hy­po­thet­i­cal RCT when de­sign­ing a non-in­ter­ven­tion­al study “is a fun­da­men­tal­ly dif­fer­ent task” than what the re­searchers did with RCT-DU­PLI­CATE.

In the case of RCT-DU­PLI­CATE, Shirley Wang, as­so­ciate pro­fes­sor of med­i­cine at Har­vard Med­ical School, ex­plained how the pro­gram sought to em­u­late 30 RCTs us­ing clin­i­cal prac­tice da­ta.

The re­searchers found that 50% of the se­lect­ed RCTs could be em­u­lat­ed close­ly re­gard­ing de­sign and analy­sis, and they saw com­pa­ra­ble treat­ment ef­fects. But RCT and RWE find­ings were more like­ly to di­verge when there were sub­stan­tive em­u­la­tion chal­lenges, which could be be­cause the data­base and RCTs are tar­get­ing dif­fer­ent ques­tions, or due to bias, or both.

Sub­stan­tive chal­lenges were seen in the re­searchers’ at­tempts to repli­cate stud­ies in os­teo­poro­sis, chron­ic kid­ney dis­ease, heart fail­ure, asth­ma and COPD, Wang said.

How­ev­er, oth­er tri­als that could be close­ly em­u­lat­ed dealt with atri­al fib­ril­la­tion, VTE and hy­per­ten­sion, where­as tri­als re­lat­ed to di­a­betes (8 tri­als) and an­tiplatelet ther­a­py (3 tri­als) saw vary­ing de­grees of chal­lenges.

“Data­base stud­ies can come to sim­i­lar con­clu­sions as RCTs when we are able to em­u­late them well. But it’s more chal­leng­ing to em­u­late tri­als that are de­signed with many con­straints to show ef­fects un­der dif­fer­ent con­di­tions,” Wang said, not­ing that it’s eas­i­er to em­u­late tri­als with more prag­mat­ic de­sign fea­tures.

“With da­ta that are fit-for-pur­pose and prop­er de­sign and analy­sis, non-ran­dom­ized RWE stud­ies can come to sim­i­lar con­clu­sions about a drug’s treat­ment ef­fect as ran­dom­ized tri­als,” Wang added.

Se­bas­t­ian Schneeweiss, pro­fes­sor of med­i­cine at Har­vard who al­so dis­cussed re­sults of the study last week, not­ed, “Most im­por­tant­ly, re­al-world ev­i­dence com­ple­ments ev­i­dence from ran­dom­ized tri­als and does not re­place it. The con­clu­sion of this demon­stra­tion project should not be that every RWE study needs to em­u­late an RCT. This would de­feat the val­ue of RWE in com­ple­ment with RCTs.”

The FDA-fund­ed Brigham Women’s re­search is still work­ing on em­u­lat­ing 7 RCTs that are on­go­ing.

Over­all, the FDA’s drug cen­ter has sup­port­ed more than 20 RWE demon­stra­tion pro­jec­tions, in­clud­ing ones re­lat­ed to im­prov­ing the use or qual­i­ty of RWD, as­sess­ing RWE study de­signs (e.g. RCT-DU­PLI­CATE), or eval­u­at­ing tools for spe­cif­ic pur­pos­es.

Back in 2018, the FDA al­so un­veiled its RWE frame­work, which has since been sup­ple­ment­ed with 4 new draft guid­ance doc­u­ments on EHRs and med­ical claims da­ta, da­ta stan­dards for RWD sub­mis­sions, as­sess­ing reg­istries to sup­port reg­u­la­to­ry de­ci­sions mak­ing, and us­ing RWD and RWE to sup­port reg­u­la­to­ry de­ci­sion-mak­ing.

But in ex­plain­ing how there are still mul­ti­ple ques­tion marks around the use of RWE, FDA’s Con­ca­to al­so high­light­ed an NE­JM ar­ti­cle from 2020, in which re­searchers from the Uni­ver­si­ty of Ox­ford wrote, “The re­place­ment of ran­dom­ized tri­als with non­ran­dom­ized ob­ser­va­tion­al analy­ses is a false so­lu­tion to the se­ri­ous prob­lem of en­sur­ing that pa­tients re­ceive treat­ments that are both safe and ef­fec­tive.”

Even FDA Com­mis­sion­er Rob Califf, who wasn’t com­mis­sion­er at the time, was on board.

Crit­i­cal sum­ma­ry state­ment on ran­dom­iza­tion. https://t.co/98g6on­pqjL

— Robert M Califf (@califf001) Feb­ru­ary 12, 2020

Despite whispers of a busy year for M&A, deal activity in the pharma space is actually down 30% on a semi-annualized basis, according to PwC’s latest report on deal activity. But don’t rule out larger deals in the second half of the year, the consultants said.

PwC pharmaceutical and life sciences consulting solutions leader Glenn Hunzinger expects to see Big Pharma companies picking up earlier stage companies to try and fill pipeline gaps ahead of a slew of big patent cliffs. Though a bear market continues to maul the biotech sector, Hunzinger said recent deals indicate that pharma companies are still paying above current trading prices.

Following the Supreme Court’s historic decision on Friday to overturn Americans’ constitutional right to an abortion after almost 50 years, Attorney General Merrick Garland sought to somewhat reassure women that states will not be able to ban the prescription drug sometimes used for abortions.

Following the decision, the New England Journal of Medicine also published an editorial strongly condemning the reversal, saying it “serves American families poorly, putting their health, safety, finances, and futures at risk.”

The story of Amryt Pharma’s candidate for the genetic skin condition epidermolysis bullosa, or EB, will soon enter another chapter.

After the Irish drugmaker’s candidate, dubbed Oleogel-S10 and marketed as Filsuvez, was handed a CRL earlier this year, the company announced in a press release that it plans to submit a formal dispute resolution request for the company’s NDA for Oleogel-S10.

North Carolina Republican Sen. Thom Tillis made a name for himself in the 2020 election cycle as the darling of the pharma industry, accepting hundreds of thousands in campaign contributions, even from the likes of Pfizer CEO Albert Bourla.

Those contributions have led Tillis to attempt to re-write patent laws in pharma’s favor, a move which failed to gain steam in 2019, and request for a third time since January that the FDA should help stop “the false narrative that patent protections are to blame for high drug prices.”