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

The FDA’s adcomm of outside vaccine experts will meet tomorrow to discuss how to protect the US from a likely coming wave of Omicron cases in the fall and winter, and whether to deploy vaccines that specifically target the Omicron variant.

While the data so far are limited, the FDA sounded an upbeat tone in the briefing documents on Pfizer/BioNTech’s candidates, released this weekend ahead of the VRBPAC meeting.

Ireland has been on a roll in 2022, with several large pharma companies announcing multimillion-euro projects. Now AstraZeneca’s rare disease outfit Alexion is looking to get in on the action.

Alexion on Friday announced a €65 million ($68.8 million) investment in new and enhanced capabilities across two sites in the country, including at College Park in the Dublin suburb of Blanchardstown and the Monksland Industrial Park in the central Irish town of Athlone, according to the Industrial Development Agency of Ireland.

As Bristol Myers Squibb braces for a court battle over a costly delay — at least for Celgene shareholders — for its CAR-T lymphoma treatment Breyanzi, the pharma giant is touting a label expansion in the second-line setting.

Breyanzi, also known as liso-cel, snagged a win on Friday in adults with large B-cell lymphoma (LBCL) who: don’t respond to chemotherapy, or relapse within 12 months; don’t respond or relapse after 12 months; or are not eligible for hematopoietic stem cell transplant after chemo due to their age or comorbidities.

Another biotech standing on shaky financial legs has fallen victim to the bears.

Merck partner 4D Pharma has reported that a key lender, Oxford Finance, shoved the UK company into administration after calling in a $14 million loan they couldn’t immediately make good on. Trading in their stock was halted with a market cap that had fallen to a mere £30 million.

“Despite the very difficult prevailing market conditions,” 4D reported on Friday, the biotech had been making progress on finding some new financing and turned to Oxford with an alternative late on Thursday and then again Friday morning.

Amidst recently broader vaccine manufacturing initiatives from the EU and European companies, the G7 summit in the mountains of Bavaria has brought about some positive news for closing vaccine and medical product manufacturing gaps around the globe.

According to a statement from the White House, the G7 leaders have formally launched the partnership for global infrastructure, PGII. The effort will aim to mobilize hundreds of billions of dollars to deliver infrastructure projects in several sectors including the medical and pharmaceutical manufacturing space.