Top Five Rules for Suc­cess in De­cen­tral­ized Tri­als

The glob­al coro­n­avirus pan­dem­ic cat­a­pult­ed the emerg­ing field of de­cen­tral­ized clin­i­cal tri­als (DCTs) to the fore­front of clin­i­cal re­search in a mat­ter of months. With new ap­proach­es like home nurs­ing, tele­health, di­rect-to-pa­tient (DTP) drug ship­ments, and mo­bile sen­sors, DCTs are mak­ing it eas­i­er for pa­tients to par­tic­i­pate in tri­als, es­pe­cial­ly for those who live far away, are too sick to trav­el, or are too busy.

Parex­el’s DCT ex­pe­ri­ence spans more than 100 ful­ly de­cen­tral­ized or hy­brid tri­als, and more than 250 tri­als with DTP drug ship­ments. Pa­tients’ needs and in­sights are cen­tral to how we de­sign and con­duct tri­als, so we talked with Parex­el DCT ex­perts to find out what they have learned. Here are their top five rules for a suc­cess­ful DCT:

1. An­tic­i­pate and mit­i­gate DCT-spe­cif­ic risks.
   Tra­di­tion­al tri­als car­ry plen­ty of risks: Miss­ing or er­ro­neous da­ta, im­prop­er drug han­dling, and ac­ci­den­tal un­blind­ing, to name a few. With DCTs, these risks may be more ob­vi­ous—and that en­ables study de­sign­ers to mit­i­gate them through care­ful plan­ning.
   For ex­am­ple, a pa­tient in a clin­i­cal tri­al al­ways has the right to with­draw from the study for any rea­son. But some ther­a­pies can’t be stopped im­me­di­ate­ly: pa­tients need to take in­creas­ing­ly low­er (titrat­ed) dos­es and ta­per off the treat­ment grad­u­al­ly for safe­ty rea­sons. In a tra­di­tion­al site-based tri­al, the titra­tion process is ex­plained and han­dled by site staff. In a DCT, we pre­pare a study-spe­cif­ic titra­tion kit that is dis­trib­uted to pa­tients at the start of the study. If they with­draw at any time, the in­struc­tions and med­ica­tion dos­es are pre-pack­aged and ready to go.“Smarter” process­es can al­so help de­liv­er in­ves­tiga­tive med­i­c­i­nal prod­ucts (IMPs). In a DCT, if we know that we must con­trol the tem­per­a­ture of an IMP from site to stor­age in a pa­tient’s home, we build lay­ered sys­tems, in­clud­ing spe­cial­ly trained couri­ers to trans­port it in a tem­per­a­ture-con­trolled en­vi­ron­ment with a mon­i­tor that pro­vides con­tin­u­ous read­outs. If an IMP drops be­low or goes above the spec­i­fied range, the couri­er does not de­liv­er it.
2. Think through every as­pect of DTP lo­gis­tics.
   Spon­sors tend to fo­cus on IMP de­liv­ery when they think about DTP lo­gis­tics, but there is a lot more to it. Ef­fec­tive DTP op­er­a­tions al­so in­volve study sup­port ma­te­ri­als (such as pa­tient in­struc­tions), de­vices, con­sum­ables, sam­ple col­lec­tion, the re­turn and rec­on­cil­i­a­tion of un­used IMP, and pack­ag­ing ma­te­ri­als, among oth­er things. Suc­cess­ful DTP lo­gis­tics re­quire at­ten­tion to de­tail and an over­all view of the IMP sup­ply and stor­age chain.
   Parex­el re­cent­ly con­duct­ed a tri­al where we sup­plied pa­tients with study-spe­cif­ic ‘smart’ re­frig­er­a­tors that reg­is­tered ac­tiv­i­ty. Since some pa­tients could not eas­i­ly ac­com­mo­date an ex­tra re­frig­er­a­tor in their home or apart­ment, we checked each par­tic­i­pant’s size and space re­quire­ments. This is the lev­el of de­tail that is nec­es­sary, yet easy to over­look, when de­vis­ing a DTP de­liv­ery sys­tem.
3. Em­brace the ex­per­tise and mo­ti­va­tion of pa­tients and their care­givers.
   Con­ven­tion­al wis­dom in the phar­ma­ceu­ti­cal in­dus­try was: “We need to re­strict in­for­ma­tion about the in­ner work­ings of clin­i­cal tri­als, or it will con­fuse and dis­cour­age pa­tients.” At Parex­el, we’ve found just the op­po­site. Pa­tients and care­givers—es­pe­cial­ly those with chron­ic and rare dis­eases—are of­ten ex­perts in their con­di­tion. And they ea­ger­ly as­sume re­spon­si­bil­i­ties in DCTs.For ex­am­ple, di­a­betes pa­tients know how to in­ject them­selves, and kids who have grown up with di­a­betes are adept with elec­tron­ics and de­vices. Pa­tients with rare and or­phan dis­eases, par­tic­u­lar­ly those who live far from aca­d­e­m­ic re­search cen­ters, are deeply knowl­edge­able and mo­ti­vat­ed.
   Since COVID-19 hit in late 2019, pa­tients in clin­i­cal tri­als have adapt­ed to new de­vices and tele­health vis­its in what The Lancet re­cent­ly called a “fast, ef­fec­tive read­just­ment.” The re­sults demon­strate that giv­ing pa­tients and care­givers more re­spon­si­bil­i­ty pro­vides enor­mous ben­e­fits.
   DCT tri­al de­sign­ers can learn a lot by ask­ing pa­tients, care­givers, and ad­vo­ca­cy groups the right ques­tions. Does the treat­ment be­ing test­ed ad­dress a rel­e­vant pa­tient need? Can it be ad­min­is­tered in a non-site set­ting? For this pa­tient pop­u­la­tion, is a DCT the right ap­proach?
4. Ad­just pro­to­cols for bet­ter com­pli­ance at home.
   If your goal is 100% pa­tient com­pli­ance for a DCT, and you have re­strict­ed time win­dows for the ac­tiv­i­ties in your pro­to­col, you are not like­ly to suc­ceed.
   For ex­am­ple, we re­cent­ly worked with a spon­sor to tweak the pro­to­col de­sign of a DCT be­cause it was un­re­al­is­tic. The study spec­i­fied that pa­tients record their blood pres­sure twice per day with­in two 90-minute win­dows over six months. How­ev­er, pa­tients with young chil­dren to care for, mo­bil­i­ty prob­lems, or chron­ic pain would have dif­fi­cul­ty do­ing that. So in­stead of keep­ing a rigid time­frame and see­ing, say, 50% com­pli­ance, we broad­ened the time win­dows and achieved 80%.
5. Ask your pa­tients to de­fine pa­tient-friend­ly.
   Of­ten tri­al plan­ners the­o­rize in meet­ings about what would work best for pa­tients, but on­ly pa­tients know. To bring that knowl­edge to plan­ning, talk with pa­tients, care­givers, and sites, and so­lic­it prac­ti­cal feed­back about what they need.
   For ex­am­ple, some pa­tients do not find home nurs­ing vis­its con­ve­nient or de­sir­able. In cer­tain cul­tures, chron­ic or se­ri­ous ill­ness or dis­abil­i­ty is taboo, a sign of weak­ness, or even a trig­ger for harsh judg­ment and shun­ning by the com­mu­ni­ty, so hav­ing nurs­es vis­it the pa­tient at home risks their pri­va­cy. Oth­ers may feel em­bar­rassed by con­strained eco­nom­ic cir­cum­stances such as sev­er­al gen­er­a­tions or many in­di­vid­u­als liv­ing in one home. Or by a psy­cho­log­i­cal dis­or­der such as hoard­ing. If re­search shows that your tar­get pa­tient pop­u­la­tion doesn’t want home nurs­ing, con­sid­er lo­cal com­mu­ni­ty cen­ters or even ho­tels for nurs­ing vis­its.

Parex­el DCT ex­perts who con­tributed to this ar­ti­cle:

Gui­do Ep­ple
In­no­va­tion Am­bas­sador and Head of Clin­i­cal Tri­al Sup­plies & Lo­gis­tics Prod­uct Man­age­ment

Alexan­dra Holzum
As­so­ciate Di­rec­tor, In­te­grat­ed So­lu­tions, Clin­i­cal Tri­al Sup­plies & Lo­gis­tics

Ju­lia Lake­land
So­lu­tions Ar­chi­tect and Pro­gram Di­rec­tor

Sarah Pilk­ing­ton
As­so­ciate Di­rec­tor, Pa­tient In­no­va­tion Cen­ter

Ada Wowk
Di­rec­tor, Pa­tient In­no­va­tion Cen­ter