Cen­tral­ize Clin­i­cal Tri­als with De­cen­tral­ized Clin­i­cal Tri­als

With ag­ile and de­cen­tral­ized ap­proach­es, spon­sors ac­tu­al­ly have more cen­tral­ized com­mand and over­sight.

One of the most no­table ear­ly us­es of the term “de­cen­tral­ized clin­i­cal tri­als” came from the pre­sid­ing FDA Com­mis­sion­er, Dr. Scott Got­tlieb, in a Jan­u­ary 2019 speech, where he not­ed that de­cen­tral­iza­tion can, “help clin­i­cal tri­als be­come ag­ile and ef­fi­cient by re­duc­ing the ad­min­is­tra­tive bur­dens on spon­sors and those con­duct­ing tri­als, and can al­low pa­tients to re­ceive treat­ments from com­mu­ni­ty providers with­out com­pro­mis­ing the qual­i­ty of the tri­al or the in­tegri­ty of the da­ta be­ing col­lect­ed,”¹

Since then, the in­dus­try has ral­lied around the term de­cen­tral­ized clin­i­cal tri­als and ex­pand­ed its de­f­i­n­i­tion to in­clude all mo­bile, re­mote, home-based or com­mu­ni­ty provider-based so­lu­tions for col­lect­ing clin­i­cal out­comes da­ta. But why use the term “de­cen­tral­ized,” and what does it re­al­ly re­fer to?  The orig­i­nal in­tent was to de­fine the in­verse for the tra­di­tion­al clin­i­cal tri­al de­sign in which the col­lec­tion of da­ta is cen­tral­ized with­in one brick and mor­tar in­ves­tiga­tive site lo­ca­tion.

While the term made so much sense in the con­text of tra­di­tion­al re­search, the irony is that the tra­di­tion­al mod­el is based on a high­ly de­cen­tral­ized net­work of in­de­pen­dent sites to col­lect out­comes da­ta. Each of these in­ves­tiga­tive sites have their own process­es, peo­ple, and tech­nol­o­gy, to ma­tric­u­late pa­tients through the tri­als they are con­duct­ing on be­half of spon­sors. As a re­sult, spon­sors can spend, on av­er­age, a quar­ter of the en­tire clin­i­cal tri­al bud­get con­duct­ing source da­ta ver­i­fi­ca­tion (SDV)² with over­sight from clin­i­cal re­search as­so­ciates (CRAs) to en­sure pro­to­col com­pli­ance.

If you step back from the sta­tus quo, this re­al­ly doesn’t feel very cen­tral­ized at all, does it?

The term “cen­tral­iza­tion” com­mon­ly refers to the con­cen­tra­tion of con­trol un­der a sin­gle au­thor­i­ty. With this de­f­i­n­i­tion, the au­thor­i­ty in the de­vel­op­ment process pre­sum­ably would be the com­pa­ny spon­sor­ing the tri­al.

By de­f­i­n­i­tion, if a clin­i­cal tri­al spon­sor were to cen­tral­ize tri­al ex­e­cu­tion, it would seek to main­tain con­trol of the process­es, peo­ple and tech­nol­o­gy re­quired to ex­e­cute the tri­al rather than leav­ing their pro­to­cols sus­cep­ti­ble to the in­her­ent in­con­sis­ten­cies and sub­se­quent cost­ly over­sight re­quired when us­ing a myr­i­ad of dis­parate in­ves­tiga­tive sites.

With­out the de­pen­den­cy on the tra­di­tion­al site net­work and its lim­it­ed ge­o­graph­ic catch­ment area, the spon­sor would have the free­dom to max­i­mize the num­ber of pa­tients who could par­tic­i­pate.  Guid­ed by an ef­fec­tive op­er­at­ing sys­tem, the spon­sor could en­sure that every in­ves­ti­ga­tor, nurse, and study co­or­di­na­tor ex­e­cute by the ex­act same stan­dard op­er­at­ing pro­ce­dures and are sup­port­ed by the ex­act same tech­nol­o­gy to en­sure com­pli­ance with a pro­to­col in an un­am­bigu­ous man­ner. The spon­sor could al­so re­quire that all of its da­ta be en­tered di­rect­ly in­to a source sys­tem for re­al-time ac­cess to study per­for­mance, thus re­duc­ing the chances of mis­in­for­ma­tion and elim­i­nat­ing the need for SDV by CRAs who need to fly all over the world.

This cen­tral­ized set of process­es, peo­ple and tech­nol­o­gy are be­ing de­ployed every­day now by Sci­ence 37 across al­most every ther­a­peu­tic area, ge­og­ra­phy and tri­al phase. Un­sur­pris­ing­ly, spon­sors that are cen­tral­iz­ing these ac­tiv­i­ties are achiev­ing up to 15x faster en­roll­ment, up to 28% greater re­ten­tion and 3x the di­ver­si­ty in their stud­ies, while en­sur­ing greater com­pli­ance, less rater vari­abil­i­ty and re­al-time vis­i­bil­i­ty to per­for­mance da­ta. Not to men­tion sig­nif­i­cant­ly re­duc­ing pa­tient bur­den.

And yet we call this cen­tral­iza­tion of process­es, peo­ple, and tech­nol­o­gy, “de­cen­tral­ized clin­i­cal tri­als.”  Go fig­ure.

The Ag­ile Clin­i­cal Tri­al:

An im­por­tant note in Dr. Got­tlieb’s orig­i­nal speech was that the de­ploy­ment of these ca­pa­bil­i­ties now known and de­cen­tral­iza­tion, leads to more “agili­ty”. To­day, many study de­signs be­ing de­ployed with de­cen­tral­ized clin­i­cal tri­al ca­pa­bil­i­ties are a hy­brid be­tween tra­di­tion­al and de­cen­tral­ized.

Many lead­ing spon­sors are sim­ply sup­ple­ment­ing their tra­di­tion­al site net­works with a vir­tu­al site, or what Sci­ence 37 refers to as a Met­a­site™, to gen­er­ate speed of en­roll­ment. Oth­er tri­als are ini­ti­at­ed at a tra­di­tion­al clin­i­cal tri­al site, with all fol­low up vis­its com­ing from the com­fort of the pa­tient’s home, to re­duce pa­tient bur­den and in­crease re­ten­tion. Still oth­ers are ini­ti­at­ed re­mote­ly, with com­mon pro­ce­dures be­ing con­duct­ed by lo­cal com­mu­ni­ty providers.

Ul­ti­mate­ly the goal of every study is to ac­cel­er­ate en­roll­ment, en­sure ef­fi­cien­cy and com­pli­ance, and gen­er­ate the high­est qual­i­ty da­ta. To ac­com­plish these goals most ef­fec­tive­ly, spon­sors need the flex­i­bil­i­ty to ex­e­cute more ag­ile clin­i­cal tri­al mod­els. This re­quires an op­er­at­ing sys­tem with stan­dard­ized process­es, cen­tral­ized net­works of pa­tients, in­ves­ti­ga­tors, nurs­es and co­or­di­na­tors, and a uni­fy­ing tech­nol­o­gy that can be used on-premise and off-premise which yield the ad­di­tion­al ben­e­fit of en­abling spon­sors to be in con­trol of their des­tiny.

To­day, more spon­sors are stan­dard­iz­ing on the Sci­ence 37 op­er­at­ing sys­tem to achieve the flex­i­bil­i­ty and con­trol re­quired to de­liv­er to­day’s more ag­ile clin­i­cal tri­al mod­els and to yield all the ben­e­fits of speed, re­ten­tion, di­ver­si­ty, low­er pa­tient bur­den, less rater vari­abil­i­ty and the high­est qual­i­ty da­ta.

To learn more vis­it www.sci­ence37.com

Ref­er­ences:

¹Got­tlieb, Scott. “Break­ing Down Bar­ri­ers Be­tween Clin­i­cal Tri­als and Clin­i­cal Care: In­cor­po­rat­ing Re­al World Ev­i­dence in­to Reg­u­la­to­ry De­ci­sion Mak­ing.” Bi­par­ti­san Pol­i­cy Cen­ter, Jan­u­ary 28, 2019, Wash­ing­ton, DC.

²BrJ Clin Phar­ma­col, Im­pact of source da­ta ver­i­fi­ca­tion on da­ta qual­i­ty in clin­i­cal tri­als: an em­pir­i­cal post hoc analy­sis of three phase 3 ran­dom­ized clin­i­cal tri­als, Oc­to­ber 19, 2014.