The next phase of de­cen­tral­iza­tion in clin­i­cal tri­als

There were 250 de­cen­tralised clin­i­cal tri­als (DCTs) world­wide in 2012. By 2021, there were 1,291. The face of clin­i­cal re­search is evolv­ing. Rather than bring­ing pa­tients to sites, study teams are now ex­plor­ing ways they can bring the tri­al to pa­tients us­ing a vary­ing com­bi­na­tion of di­rect-to-pa­tient drug ship­ments, home nurs­ing, video con­fer­enc­ing, and elec­tron­ic da­ta col­lec­tion. The re­sult is an im­proved ex­pe­ri­ence for pa­tients, whose par­tic­i­pa­tion no longer rests on long jour­neys to and from sites.

Ac­cord­ing to Daniel Tan­ner, chief com­mer­cial of­fi­cer at Cer­ba Re­search, this pa­tient-cen­tric­i­ty comes with ex­cit­ing pos­si­bil­i­ties to im­prove tri­als for all stake­hold­ers. “Clin­i­cal tri­als were re­al­ly not op­ti­mized from the per­spec­tive of the pa­tient, site or the spon­sor; they are in­creas­ing­ly cost in­ef­fec­tive, and they take a lot of time. De­cen­tral­iza­tion has the po­ten­tial to solve a lot of these chal­lenges, par­tic­u­lar­ly around par­tic­i­pa­tion rates but al­so im­por­tant­ly around di­ver­si­ty.”

Lim­it­ed par­tic­i­pa­tion has been a thorn in the in­dus­try’s side for many years now, with low-en­rolling sites a like­li­hood for vir­tu­al­ly any study. As Tan­ner men­tions, clin­i­cal tri­als have al­so been crit­i­cized for their lack of par­tic­i­pant di­ver­si­ty. So­cioe­co­nom­ic fac­tors can con­tribute to ac­cess dif­fi­cul­ty for mi­nor­i­ty groups, and a shift to de­cen­tral­ized tri­als (DCTs) could lift this bur­den.

“Any­thing we can do to make it eas­i­er for pa­tients to take part in a tri­al should re­al­ly help us to re­cruit and re­tain pa­tients bet­ter, which means stud­ies can be com­plet­ed faster and more cost-ef­fec­tive­ly,” he ex­plains. “We can al­so op­ti­mize ef­fi­cien­cy from a site per­spec­tive, which should mean bet­ter pa­tient safe­ty out­comes and da­ta qual­i­ty whilst po­ten­tial­ly en­abling them to par­tic­i­pate in more re­search. For spon­sors, the ben­e­fits are clear be­cause they should be able to de­vel­op new ther­a­pies faster and more ef­fi­cient­ly, which ul­ti­mate­ly ben­e­fits all of us, par­tic­u­lar­ly if they are more rep­re­sen­ta­tive.”

There is da­ta to sup­port this pos­si­bil­i­ty. Ac­cord­ing to an in­ves­ti­ga­tion by the Tufts CS­DD, DCT de­ploy­ments were as­so­ci­at­ed with re­duced tri­al time­lines, as well as net fi­nan­cial ben­e­fits rang­ing from five to 14 times for Phase II and III tri­als re­spec­tive­ly.^[1]

Mak­ing the tran­si­tion

The num­ber of de­cen­tral­ized clin­i­cal tri­als has steadi­ly in­creased over the past decade, ris­ing from 250 in 2012 to 1,291 in 2021. They are ex­pect­ed to peak even high­er in 2022, with Glob­al­Da­ta fore­cast­ing the in­dus­try to hold ap­prox­i­mate­ly 1,425 DCTs by the end of the year.^[2]

With such pro­found ben­e­fits to be gained from de­cen­tral­iza­tion, some may won­der why their adop­tion is not high­er. But the phar­ma­ceu­ti­cal in­dus­try has been nat­u­ral­ly risk-averse and slow to adopt new ap­proach­es, says Tan­ner.

“With­in such a tight­ly reg­u­lat­ed in­dus­try, there is nat­ur­al ap­pre­hen­sion to be­ing a first mover. While there are huge re­turns when you get it right, there’s al­so enor­mous amounts of risk and con­tin­u­ous pres­sure con­cern­ing pa­tient safe­ty and da­ta in­tegri­ty which have in­hib­it­ed our abil­i­ty to move quick­ly.”

De­spite this, dur­ing the Covid-19 pan­dem­ic, ne­ces­si­ty re­al­ly did prove it­self the moth­er of in­ven­tion. “Covid had an enor­mous im­pact not just on clin­i­cal tri­als, but the en­tire world,” Tan­ner re­marks. “Every­body got used to do­ing things re­mote­ly. Drug de­vel­op­ment had to change. Many tri­als have had el­e­ments of de­cen­tral­iza­tion for some time, so there were things in place that meant that when the con­di­tions pre­cip­i­tat­ed it, there was a fair­ly quick move.”

Post Covid, he be­lieves de­cen­tral­ized tri­als are now “part of the toolk­it” and are like­ly to be de­ployed at least in some de­gree to “every­thing that we do go­ing for­wards”.

But there are still many chal­lenges to con­front on this jour­ney. First, there’s the change man­age­ment ob­sta­cle, which in­volves fig­ur­ing out how to align all stake­hold­ers on a new ap­proach and un­der­stand­ing what process­es need to change for a suc­cess­ful tran­si­tion. At the end of the day, com­pli­ance and pa­tient safe­ty will be first and fore­most for spon­sors, but the com­plex­i­ty of some tri­als can make this dif­fi­cult in a de­cen­tral­ized set­ting.

“Ecosys­tems, tech­nol­o­gy, reg­u­la­tions, and even cul­tures are all dif­fer­ent from one coun­try to an­oth­er, which adds com­plex­i­ty,” ex­plains Tan­ner. “The re­al­i­ty is that cer­tain pro­to­cols, stud­ies, and lo­ca­tions will lend them­selves more read­i­ly to de­cen­tral­ized tri­als, where­as many oth­ers would prove in­cred­i­bly chal­leng­ing.”

Study teams are grap­pling with well-known ob­sta­cles on the op­er­a­tional side, too. These in­clude the lo­gis­tics of ship­ping in­ves­tiga­tive med­i­c­i­nal prod­ucts to pa­tients, with less con­trol over the drugs be­ing stored and ad­min­is­tered cor­rect­ly.

Ar­rang­ing blood draws for bi­o­log­i­cal test­ing has al­so be­come a chal­lenge. Mo­bile nurs­ing is the pri­ma­ry so­lu­tion, but these ser­vices are lim­it­ed in sup­ply. High de­mand has raised their costs and caused sched­ul­ing chal­lenges. Re­cent in­no­va­tions in au­to-phle­boto­my tech­nol­o­gy could help pa­tients draw their own blood in the fu­ture, mean­while, some cen­tral lab­o­ra­to­ries such as Cer­ba Re­search now of­fer dried blood spot test­ing ser­vices. This method in­volves us­ing a small lancet to cre­ate a tiny in­ci­sion. Small droplets of blood are then ab­sorbed in­to a fil­ter pa­per, pro­vid­ing an eas­i­er blood draw for the pa­tient and an ef­fec­tive biosam­pling method for DCTs.

The next phase

Pa­tient cen­tric­i­ty has been the goal of the clin­i­cal tri­al in­dus­try for some time now, and the huge leap for­ward catal­ysed by the pan­dem­ic must now be built on. One ex­am­ple is the in­creas­ing fo­cus on in­cor­po­rat­ing the pa­tient’s per­spec­tive in­to new study de­signs. It re­quires teams to en­gage with pa­tients di­rect­ly. Mak­ing ef­forts to bet­ter un­der­stand tri­al de­signs through par­tic­i­pants’ eyes will be an im­por­tant ac­tion as the in­dus­try moves ahead to the next phase.

“De­cen­tralised tri­als are just one ex­am­ple of how as an in­dus­try we can move away from the tra­di­tion­al mod­el of drug de­vel­op­ment,” be­lieves Tan­ner. “Be­cause we have this greater par­tic­i­pa­tion and these new re­search mod­els, we can start to think big­ger. We should not be view­ing clin­i­cal tri­als as dis­crete events but try to take a more lon­gi­tu­di­nal ap­proach to en­gage in­di­vid­u­als with re­search on new drugs, vac­cines, di­ag­nos­tics, and bio­mark­ers.”

Cer­ba Re­search is now work­ing hard to de­fine the po­si­tion of med­ical lab­o­ra­to­ries with­in this wider vi­sion. “At Cer­ba, it be­came ap­par­ent to our team that we can ei­ther be a pas­sive par­tic­i­pant in the mar­ket or we can ac­tive­ly try to cre­ate this new par­a­digm. At the start of Covid we up­dat­ed our strate­gic im­per­a­tives to put de­cen­tralised tri­als as a key pil­lar,” Tan­ner says.

Ref­er­ences

^[1] https://www.busi­ness­wire.com/news/home/20220113005740/en/New-Study-De­cen­tral­ized-Clin­i­cal-Tri­als-Can-Achieve-Net-Fi­nan­cial-Ben­e­fits-of-5X-to-14X-Due-to-Re­duced-Tri­al-Time­lines-and-Oth­er-Fac­tors

^[2] The Move­ment To­wards De­cen­tral­ized Clin­i­cal Tri­als, Glob­al­Da­ta, Oc­to­ber 2022