The val­ue of pub­lish­ing clin­i­cal tri­al da­ta can­not be ex­ag­ger­at­ed — it is cru­cial to the pace and di­rec­tion of sci­en­tif­ic progress, and crit­i­cal to the knowl­edge base em­ployed by pa­tients, doc­tors and pol­i­cy­mak­ers to make de­ci­sions about the safe­ty, ben­e­fits and adop­tion of treat­ment in­ter­ven­tions. But not every­body is quite as con­cerned with the toll clin­i­cal tri­al trans­paren­cy trans­gres­sions can take on pa­tient health, pub­lic health pol­i­cy and med­ical ad­vance­ment — a new re­port sug­gests Eu­ro­pean Uni­ver­si­ties are ex­tra­or­di­nar­i­ly guilty of these re­port­ing vi­o­la­tions.

The re­port, pub­lished on Tues­day, eval­u­at­ed the per­for­mance of 30 Eu­ro­pean uni­ver­si­ties that have spon­sored the largest num­ber of clin­i­cal tri­als gov­erned by the Eu­ro­pean Union. Since 2014, the EU has man­dat­ed every study reg­is­tered on the EU clin­i­cal tri­als reg­istry post sum­ma­ry re­sults on­to the reg­istry with­in one year of com­ple­tion (6 months for pe­di­atric tri­als) — these rules al­so ap­ply to tri­als com­plet­ed pri­or to 2014, and must be ad­hered to ir­re­spec­tive of whether re­sults have been pub­lished in aca­d­e­m­ic jour­nals.

Al­to­geth­er the eval­u­at­ed uni­ver­si­ties have spon­sored 4,575 clin­i­cal tri­als, of which re­sults are ver­i­fi­ably due for 940 tri­als. But on­ly the re­sults of 162 (17%) tri­als have been post­ed on the EU Clin­i­cal Tri­als Reg­is­ter, the re­port found. Da­ta for the study was col­lat­ed and analysed by a con­sor­tium of Eu­ro­pean in­sti­tu­tions: UK’s TranspariMED, Ger­many’s BUKO Phar­ma-Kam­pagne, Bel­gium’s Test Aankoop and Nether­land’s Health Ac­tion In­ter­na­tion­al (HAI).

“Fail­ure to ful­ly and rapid­ly re­port clin­i­cal tri­al re­sults is not a vic­tim­less crime…Some (UK) uni­ver­si­ties have al­ready post­ed over 90% of their tri­al re­sults, show­ing that where there is a will, there is a way. Why are uni­ver­si­ties that break the rules still re­ceiv­ing pub­lic funds to run ad­di­tion­al tri­als?” Till Bruck­n­er, founder of TranspariMED said in a state­ment. Truck­n­er co-au­thored a re­port in 2017 that analysed six drug case stud­ies — in­clud­ing Vioxx and Tam­i­flu — in which tri­al opac­i­ty di­rect­ly harmed pa­tients, tax­pay­ers and/or in­vestors.

In the cur­rent analy­sis, most of the 778 clin­i­cal tri­als ver­i­fi­ably miss­ing re­sults were run by uni­ver­si­ties in Den­mark (246 tri­als), Aus­tria (225), and Ger­many (117) and none of the as­sessed uni­ver­si­ties in France, Italy, Nor­way and Swe­den have made a sin­gle clin­i­cal tri­al re­sult pub­lic on the reg­istry, the re­port found.

Da­ta ex­tract­ed from the EU Clin­i­cal Tri­als Reg­is­ter via the EU Tri­als Track­er. Ac­cu­rate as of 01 April 2019.

Click on the im­age to see the full-sized ver­sion

These num­bers above may not even re­flect the ac­tu­al state of af­fairs, giv­en that many tri­als list­ed as “on­go­ing” on the Eu­ro­pean tri­al reg­istry were in fact com­plet­ed long ago, re­searchers un­der­scored. As it stands, EU uni­ver­si­ties are em­pow­ered to up­load their sum­ma­ry re­sults on­to the EU reg­istry as tri­al spon­sors, but they can­not di­rect­ly up­date the sta­tus (on­go­ing/com­plet­ed) of the tri­als. In­stead, uni­ver­si­ties are sup­posed to no­ti­fy their na­tion­al med­i­cines reg­u­la­tor when a tri­al is com­plet­ed, and the reg­u­la­tor is then meant to re­vise the tri­al’s sta­tus on the reg­istry. “For ex­am­ple, uni­ver­si­ties in the Nether­lands have run 967 tri­als in to­tal, but on­ly 23 of those (2.4%) are marked as “com­plet­ed”. This num­ber is com­plete­ly im­plau­si­ble, as reg­istry records show that many of those tri­als start­ed over five years ago. (In the UK, where a reg­istry up­date is on­go­ing, the pro­por­tion of “com­plet­ed” tri­als in the co­hort is 27.4%.),” the re­port not­ed.

A po­ten­tial rea­son why EU re­searchers  — who are not fac­ing the same lev­el of scruti­ny as their UK coun­ter­parts — have not both­ered with com­ply­ing with their trans­paren­cy oblig­a­tions could be the lack of in­cen­tive, Test Aankoop’s Van Hecke Mar­tine told End­points News. “The fo­cus of re­searchers is pub­li­ca­tion of their study re­sults in sci­en­tif­ic jour­nals, as this is re­ward­ed in their pro­fes­sion­al eval­u­a­tion and so it’s im­por­tant for their ca­reer.”

The on­ly bright spark in the re­port were UK uni­ver­si­ties — some of which have re­port­ing rates of over 90%, large­ly due to en­dur­ing pres­sure from par­lia­ment, the pub­lic and re­search fund­ing bod­ies. Out­side of the UK, 730 out of 785 ver­i­fi­ably due tri­als (93%) are cur­rent­ly miss­ing re­sults, da­ta in­di­cat­ed.

“There is no good rea­son why, if UK uni­ver­si­ties can do it, their coun­ter­parts across Eu­rope can’t. This should be the stim­u­lus oth­ers need to get their act to­geth­er and meet their trans­paren­cy oblig­a­tions. The ap­par­ent con­tempt shown by many Uni­ver­si­ties must not be al­lowed to stand.” HAI se­nior pol­i­cy ad­vi­sor An­cel.la San­tos told End­points News.

Once up­on a time, UK uni­ver­si­ties were sim­i­lar­ly lax about their re­port­ing oblig­a­tions. But con­cert­ed pres­sure has yield­ed im­pres­sive re­turns. For ex­am­ple, King’s Col­lege Lon­don en­hanced its re­port­ing rate from a woe­ful 18% to a re­spectable 93% with­in six months. The Uni­ver­si­ty of Not­ting­ham — spot­light­ed by the UK par­lia­ment’s sci­ence and tech­nol­o­gy com­mit­tee for its weak per­for­mance last year — has now post­ed the sum­ma­ry re­sults of over 95% of its tri­als, the re­port not­ed.

But da­ta com­piled by Ben Goldacre, best-sell­ing au­thor, med­ical doc­tor and re­searcher who fo­cus­es on un­pack­ing the mis­use of sci­ence and sta­tis­tics in his books Bad Sci­ence and Bad Phar­ma, out of his lab at the Uni­ver­si­ty of Ox­ford sug­gests that UK uni­ver­si­ties are less re­li­able than drug de­vel­op­ers at ful­fill­ing their clin­i­cal tri­al re­port­ing oblig­a­tions.

Across the At­lantic things aren’t much bet­ter. An analy­sis pub­lished last month by Uni­ver­si­ties Al­lied for Es­sen­tial Med­i­cines (UAEM) and non-prof­it re­search ad­vo­ca­cy group TranspariMED showed that 40 lead­ing US uni­ver­si­ties should have post­ed the re­sults of 450 clin­i­cal tri­als — but over a third (31%) of those re­sults are miss­ing.

Im­age: Shut­ter­stock

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.

With some an­a­lysts bet­ting on a $900,000 price for the β-tha­lassemia treat­ment in Eu­rope, where reg­u­la­tors pro­vid­ed a con­di­tion­al ear­ly OK, blue­bird CEO Nick Leschly said Fri­day morn­ing that the pa­tients who are suc­cess­ful­ly treat­ed with their drug over 5 years will be charged twice that — $1.8 mil­lion — on the con­ti­nent. That makes this drug the sec­ond most ex­pen­sive ther­a­py on the plan­et, just be­hind No­var­tis’ new­ly ap­proved Zol­gens­ma at $2.1 mil­lion, with an­a­lysts still wait­ing to see what kind of pre­mi­um can be had in the US.

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

Re­gen­eron’s high-pro­file bis­pe­cif­ic REGN1979 is back in the spot­light at the Eu­ro­pean Hema­tol­ogy As­so­ci­a­tion sci­en­tif­ic con­fab. And while the stel­lar num­bers we saw at ASH have erod­ed some­what as more blood can­cer pa­tients are eval­u­at­ed, the re­sponse rates for this CD3/CD20 drug re­main high.

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.

In­vestors are in no mood to hear biotechs tout the suc­cess of a “key” sec­ondary end­point when the piv­otal Phase III flunks the pri­ma­ry goal. Just ask Savara. 

The Texas biotech $SVRA went look­ing for a sil­ver lin­ing as com­pa­ny ex­ecs blunt­ly con­ced­ed that Mol­gradex, an in­haled for­mu­la­tion of re­com­bi­nant hu­man gran­u­lo­cyte-macrophage colony-stim­u­lat­ing fac­tor (GM-CSF), failed to spur sig­nif­i­cant­ly im­proved treat­ment out­comes for pa­tients with a rare res­pi­ra­to­ry dis­ease called au­toim­mune pul­monary alve­o­lar pro­teinosis, or aPAP.

Late-stage da­ta pre­sent­ed at the Amer­i­can Di­a­betes As­so­ci­a­tion an­nu­al meet­ing in 2010 pushed Eli Lil­ly to put a crimp on teplizum­ab as the phar­ma gi­ant found it un­able to re­set the clock on new­ly di­ag­nosed type 1 di­a­betes. At the same con­fer­ence but in dif­fer­ent hands nine years lat­er, the drug is mak­ing a crit­i­cal come­back by scor­ing suc­cess in an­oth­er niche: de­lay­ing the on­set of the dis­ease.

In a Phase II tri­al with 76 high-risk in­di­vid­u­als — rel­a­tives of pa­tients with type 1 di­a­betes who have di­a­betes-re­lat­ed au­toan­ti­bod­ies in their bod­ies — teplizum­ab al­most dou­bled the me­di­an time of di­ag­no­sis com­pared to place­bo (48.4 months ver­sus 24.4 months). The haz­ard ra­tio for di­ag­no­sis was 0.41 (p=0.006).