De­cen­tral­iza­tion: An Eth­i­cal Oblig­a­tion

Near­ly every clin­i­cal tri­al, re­gard­less of in­di­ca­tion or phase, should be ag­ile—in­cor­po­rat­ing tech­nol­o­gy and de­cen­tral­ized ap­proach­es—to make drug and ther­a­py de­vel­op­ment faster, eas­i­er and more rep­re­sen­ta­tive.

60 Years of Ex­clud­ing Pa­tients

For more than 60 years, the tra­di­tion­al clin­i­cal tri­al mod­el has re­lied on a dis­parate net­work of in­de­pen­dent in­ves­ti­ga­tor sites to find, en­roll, and ma­tric­u­late pa­tients through a study to de­ter­mine drug ef­fi­ca­cy and safe­ty. To par­tic­i­pate, each of these sites must es­tab­lish their own process­es, peo­ple, and tech­nol­o­gy to ac­com­mo­date clin­i­cal tri­als, which cre­ates a sig­nif­i­cant bar­ri­er to en­try. As a re­sult, less than three per­cent¹ of all health­care providers par­tic­i­pate as clin­i­cal tri­al in­ves­ti­ga­tors.

Once up and run­ning, this ex­clu­sive num­ber of in­ves­ti­ga­tors has the abil­i­ty to re­cruit pa­tients in­to clin­i­cal tri­als, how­ev­er, as you’d ex­pect, these re­cruit­ment ef­forts tend to be lim­it­ed to pa­tients from their prac­tice or those who live in the vicin­i­ty. So, what hap­pens if you’re not lucky enough to live near a re­search site?

Un­for­tu­nate­ly, for more than 90% of pa­tients², it means you would be ex­clud­ed from par­tic­i­pat­ing, and this ex­clu­sion comes at a cost. And enor­mous con­se­quences.

The Con­se­quences of Ex­clu­sion

Eco­nom­ic and so­cial con­se­quences

It’s well doc­u­ment­ed now that more than 80% of tri­als fail to com­plete on time³ and the num­ber-one cause for these de­lays is the speed of pa­tient en­roll­ment. Every day a drug is de­layed from com­mer­cial­iza­tion rep­re­sents $600k to $8M of lost com­mer­cial rev­enue for drug spon­sors.

Not on­ly do these de­lays rep­re­sent an op­por­tu­ni­ty cost, but they al­so de­lay the time it takes to bring vi­able prod­ucts and po­ten­tial­ly life-sav­ing ther­a­pies to the pa­tients who need them most.

Ex­clu­sion al­so means that cer­tain pop­u­la­tions do not get ac­cess. To­day, the per­cent­age of peo­ple of col­or who par­tic­i­pate in tri­als is on­ly about one third rep­re­sen­ta­tive of the U.S. pop­u­la­tions. Which means the pop­u­la­tion on whom the drug was test­ed is not nec­es­sar­i­ly rep­re­sen­ta­tive of the pop­u­la­tion of pa­tients tak­ing the drug. This is a sig­nif­i­cant prob­lem giv­en that 20% of ap­proved drugs per­form dif­fer­ent­ly by race ⁴.

Per­son­al con­se­quences

Be­yond the macro eco­nom­ic and so­cial con­se­quences, ex­clu­sion as a re­sult of the tra­di­tion­al site-based ap­proach leads to con­se­quences that hit clos­er to home for many of us.

Think about it: do you have a loved one with a med­ical con­di­tion, but has nev­er been in­vit­ed to join a clin­i­cal tri­al? How many of those whom you care deeply about have a con­di­tion that make them el­i­gi­ble for one of the more than 100,000 ac­tive stud­ies that are list­ed on Clin­i­cal­Tri­als.gov to­day? And how many of those tri­als have they been ap­proached to par­tic­i­pate in?

The ethics of ex­clu­sion hit home for me and my fam­i­ly. Not too long ago, a fam­i­ly mem­ber was di­ag­nosed with Amy­otroph­ic lat­er­al scle­ro­sis (ALS). Know­ing I was in the clin­i­cal re­search in­dus­try, he and his wife came to me in des­per­a­tion to help find a clin­i­cal tri­al that might help turn the course of this ter­ri­ble dis­ease. While I poured through the more than 200 ALS tri­als list­ed on Clin­i­cal­Tri­als.gov that were ac­tive­ly en­rolling, none were avail­able any­where close to him, and he didn’t feel con­fi­dent that he could make the long jour­ney to par­tic­i­pate giv­en his con­di­tion. Sad­ly, this fam­i­ly mem­ber went through the full, ag­o­niz­ing dis­ease pro­gres­sion, and is not with us to­day.

I know this ex­pe­ri­ence is not unique to my fam­i­ly, and this is­sue doesn’t nec­es­sar­i­ly have to be about life and death. There are too many ex­am­ples to count about the ways ac­cess to clin­i­cal tri­als could have helped peo­ple – across all con­di­tions – while en­abling faster, safer, and more ef­fi­cient re­search. I am sure you can cite an ex­am­ple or two in your own life where ac­cess would have or could make an enor­mous dif­fer­ence to­day.

Our Eth­i­cal Oblig­a­tion: En­able Uni­ver­sal Ac­cess

As a board mem­ber of the As­so­ci­a­tion of Clin­i­cal Re­search Or­ga­ni­za­tion (ACRO), I was hon­ored to par­tic­i­pate in the or­ga­ni­za­tion’s 20^th an­niver­sary cel­e­bra­tion a cou­ple weeks ago where I was touched by a pro­found state­ment by Dr. Janet Wood­cock, for­mer Food and Drug Ad­min­is­tra­tion (FDA) Com­mis­sion­er, who de­clared, “Ac­cess to clin­i­cal re­search is a right for any pa­tient.”

Of course, ac­cess should be a right for any pa­tient; how­ev­er, if we con­tin­ue to my­opi­cal­ly fo­cus on a tra­di­tion­al site-based ap­proach to pa­tient re­cruit­ment we will nev­er get there.

To­day, we live in a world where we have the ca­pa­bil­i­ty to reach any­one, any­where uti­liz­ing de­cen­tral­ized clin­i­cal tri­al tech­niques and more ag­ile clin­i­cal tri­al de­signs, and we have an eth­i­cal oblig­a­tion to im­ple­ment them. There are no ex­cus­es. We all must em­brace and lever­age de­cen­tral­iza­tion to en­able uni­ver­sal ac­cess for any­one.

A Mul­ti­tude of Op­tions: Ag­ile Ap­proach­es

For­tu­nate­ly, you don’t nec­es­sar­i­ly have to let go of your tra­di­tion­al sites com­plete­ly. In­stead, as a pi­o­neer in de­cen­tral­ized ap­proach­es, Sci­ence 37 has de­vel­oped an op­er­at­ing sys­tem (OS) to pro­vide a mul­ti­tude of op­tions and will help to as­sess your pro­to­cols to iden­ti­fy ways to en­able de­cen­tral­iza­tion.

That can man­i­fest by adding the Sci­ence 37 OS as a vir­tu­al site or Met­a­site™ to sup­ple­ment a tra­di­tion­al brick-and-mor­tar site net­work. In this case, you just elim­i­nate the bot­tom 10% of your sites, and re­place it with a sin­gle, vir­tu­al site tar­get­ing the more than 90% of the pop­u­la­tion who don’t live near your oth­er brick and mor­tar site lo­ca­tions.  When Sci­ence 37 acts as a vir­tu­al site among a tra­di­tion­al brick and mor­tar net­work, it is – at min­i­mum – the high­est en­rolling site and we of­ten rep­re­sent 50%-85% of the en­tire par­tic­i­pant vol­ume.

The Sci­ence 37 OS can be de­ployed to find and en­roll pa­tients from any­where, with study-spe­cif­ic pro­ce­dures con­duct­ed via telemed­i­cine, in-home nurs­es, or even lo­cal com­mu­ni­ty providers. When study-spe­cif­ic pro­ce­dures re­quire spe­cial­ized train­ing, tra­di­tion­al clin­i­cal tri­al sites may be used to per­form these pro­ce­dures, but pa­tient bur­den can be dra­mat­i­cal­ly re­duced to en­able fol­low up via telemed­i­cine, in-home nurs­es, or lo­cal providers.

There are count­less ag­ile de­signs in­cor­po­rat­ing de­cen­tral­ized clin­i­cal tri­al tech­niques to make clin­i­cal re­search sig­nif­i­cant­ly faster, eas­i­er, and more rep­re­sen­ta­tive. To date, the Sci­ence 37 OS has achieved up 15x faster en­roll­ment, sav­ing cru­cial time in bring­ing drugs to mar­ket. It has al­so yield­ed up to 28% greater pa­tient re­ten­tion, which has ex­tra­or­di­nary ben­e­fit for long dur­ing and long-term fol­low up stud­ies. And our OS has been proven to im­prove di­ver­si­ty by up to 3x rel­a­tive to tra­di­tion­al stud­ies.

A Call-to-Ac­tion

It’s in­cum­bent on all of us to un­equiv­o­cal­ly ad­vo­cate for more eq­ui­table ac­cess to clin­i­cal re­search and clin­i­cal tri­als par­tic­i­pa­tion. We can do it now with more ag­ile ap­proach­es and we must do it now. It’s our eth­i­cal oblig­a­tion to pa­tients, providers and to each oth­er.

Ref­er­ences:

¹https://aca­d­e­m­ic.oup.com/jn­ci/ar­ti­cle/111/3/245/5307078?lo­gin=false
²https://www.ncbi.nlm.nih.gov/pmc/ar­ti­cles/PMC7342339/
³https://ja­manet­work.com/jour­nals/ja­ma/ar­ti­cle-ab­stract/2762311#:~:text=Based%20on%20da­ta%20for%2063,es­ti­mat­ed%20to%20be%20%241336%20mil­lion
⁴https://www.sci­encedi­rect.com/sci­ence/ar­ti­cle/pii/S245186541630093X