FSP and COVID-19: Im­pact on Clin­i­cal Tri­al De­vel­op­ment


In an al­ready chal­leng­ing clin­i­cal tri­al en­vi­ron­ment, the COVID-19 era has ex­ac­er­bat­ed un­cer­tain­ty on an un­prece­dent­ed scale. In a mat­ter of days, bio­phar­ma­ceu­ti­cal com­pa­nies faced the chal­lenges of har­ness­ing all avail­able re­sources and ex­per­tise at warp speed to be­gin de­vel­op­ment of po­ten­tial vac­cines and treat­ments for COVID-19, while al­so keep­ing mis­sion crit­i­cal non-COVID tri­als mov­ing.

The func­tion­al ser­vice provider (FSP) out­sourc­ing mod­el en­ables spon­sors to ef­fi­cient­ly and cost-ef­fec­tive­ly man­age work­force needs across clin­i­cal port­fo­lios. FSP mod­els proved to be a strate­gic as­set dur­ing the coro­n­avirus pan­dem­ic when the abil­i­ty to in­crease re­source flex­i­bil­i­ty and pro­vide tar­get­ed ac­cess to spe­cif­ic ex­per­tise be­came crit­i­cal to clin­i­cal tri­al con­ti­nu­ity.

Staff aug­men­ta­tion FSP mod­els helped many bio­phar­ma com­pa­nies mit­i­gate COVID-19 era chal­lenges, in­clud­ing the abil­i­ty to man­age un­pre­dictable work vol­umes, and ac­cess high­ly skilled pro­fes­sion­als rapid­ly to help doc­u­ment scores of pro­to­col and process de­vi­a­tions. Three main ar­eas where FSP mod­els are mak­ing a sig­nif­i­cant im­pact are clin­i­cal op­er­a­tions, drug safe­ty and bio­sta­tis­tics.

Clin­i­cal op­er­a­tions

The re­quired shift to re­mote work­ing cat­alyzed the im­por­tance of flex­i­bil­i­ty and scal­a­bil­i­ty to meet time­lines and keep clin­i­cal tri­al ac­tiv­i­ties mov­ing. As spon­sors, sites, CROs and reg­u­la­tors all ad­just­ed to work­ing from home, an im­por­tant glob­al chal­lenge cen­tered on how to re­mote­ly mon­i­tor pa­tient da­ta. In­sti­tu­tions that haven’t tra­di­tion­al­ly been open to re­mote re­view of elec­tron­ic med­ical records (EMR) were forced to ac­cept and im­ple­ment re­mote process­es to main­tain clin­i­cal tri­al con­ti­nu­ity. De­spite past re­sis­tance, EMRs are now more wide­ly avail­able for mon­i­tors to re­view re­mote­ly. These suc­cess­es in clin­i­cal op­er­a­tions will ac­ti­vate pos­i­tive change, in­creas­ing ac­cep­tance of re­mote mon­i­tor­ing and source da­ta go­ing for­ward.

For many spon­sors, the abil­i­ty to quick­ly and flex­i­bly shift clin­i­cal re­sources across dif­fer­ent stud­ies or pro­grams is al­so an ef­fec­tive strat­e­gy to de­liv­er re­sults with lim­it­ed re­sources. For ex­am­ple, one Parex­el cus­tomer quick­ly re-de­ployed re­sources with­in an FSP mod­el and ear­ly clin­i­cal de­vel­op­ment CRAs from oth­er clin­i­cal tri­al pro­grams to mon­i­tor a high pri­or­i­ty clin­i­cal study that eval­u­at­ed the safe­ty and ef­fi­ca­cy of an FDA-ap­proved pre­scrip­tion med­i­cine in pa­tients with COVID-19. The ap­proach was ac­cel­er­at­ed with the U.S.-based team and the team was trained in less than a week. The ex­pe­ri­enced mon­i­tors were able to quick­ly piv­ot to a non­tra­di­tion­al mon­i­tor­ing ap­proach, which was con­duct­ed en­tire­ly re­mote­ly and fo­cused on pa­tient safe­ty, pro­to­col com­pli­ance and tar­get­ed source da­ta ver­i­fi­ca­tion of crit­i­cal da­ta points.

Oth­er un­ex­pect­ed, but pos­i­tive out­comes from al­ter­na­tive ap­proach­es forced teams to re­think the ra­tio­nale be­hind tra­di­tion­al time­lines. Some ac­tiv­i­ties, such as in­ter­nal ap­proval of a pro­to­col, have seen a dra­mat­ic time­line com­pres­sion from months or weeks to lit­er­al­ly hours, which will no doubt ex­tend in­to the post-COVID era.

Drug Safe­ty

With­in drug safe­ty, safe­ty da­ta are still be­ing re­port­ed, but not in the tra­di­tion­al ways. COVID-19 dis­rup­tions at the site lev­el have con­tributed to many in­com­plete and/or in­cor­rect re­ports. Ac­cess to skilled safe­ty spe­cial­ists is es­sen­tial to cor­rect these is­sues and fill im­por­tant gaps with the da­ta. In Parex­el’s case, we pro­vid­ed safe­ty FSP re­sources with deep foun­da­tion­al knowl­edge. We re­lied on more ex­pe­ri­enced team mem­bers for prob­lem solv­ing to meet reg­u­la­to­ry time­lines and en­sure the qual­i­ty of the fil­ings. We al­so tapped in­to in­ter­nal re­sources and used more gen­er­al­ly skilled re­sources to help with case pro­cess­ing and the full-time ef­fort re­quired for doc­u­ment­ing de­vi­a­tion notes to file.

In one case, Parex­el’s safe­ty team was called up­on to as­sist in a (lit­er­al) overnight tran­si­tion over from a trans­ac­tion­al out­sourc­ing re­la­tion­ship to pro­vide busi­ness con­ti­nu­ity. The team was quick to map out worst case sce­nar­ios and de­vel­op al­ter­na­tive strate­gies to en­sure reg­u­la­to­ry time­lines were still met by adding more trained sources as well as in­creas­ing work hours through split-shift sched­ules.

Since drug safe­ty is a tra­di­tion­al­ly an of­fice-based func­tion, an­oth­er ma­jor chal­lenge in­volved en­sur­ing a rapid and sta­ble tran­si­tion to re­mote-based work­ing. While con­ti­nu­ity plans and in­fra­struc­ture re­quire­ments were al­ready in place, ad­di­tion­al quick ac­tions in­clud­ed con­fir­ma­tion of ad­e­quate in­ter­net con­nec­tiv­i­ty as well as as­sur­ance of the ap­pro­pri­ate re­mote work­ing en­vi­ron­ment for em­ploy­ees ac­cus­tomed to of­fice work through fre­quent staff out­reach and pres­sure test­ing op­ti­mal use cas­es for video and au­dio for­mats.

Bio­sta­tis­tics and Sta­tis­ti­cal Pro­gram­ming

COVID-19 caused dis­rup­tions which sig­nif­i­cant­ly im­pact­ed da­ta qual­i­ty and in­tegri­ty, and con­se­quent­ly, the cred­i­bil­i­ty of study re­sults. Sta­tis­ti­cal analy­sis plans can be amend­ed based on how pro­to­col de­vi­a­tions re­lat­ed to COVID-19 will be han­dled for the pre­spec­i­fied analy­ses by ei­ther adding a mod­i­fied full analy­sis set or im­ple­ment­ing sen­si­tiv­i­ty analy­ses. The FDA pro­vid­ed guid­ance in March 2020 on how to ad­dress chal­lenges due to COVID-19 for da­ta qual­i­ty and in­tegri­ty due to miss­ing da­ta, lack of con­sis­ten­cy, and in­creased vari­abil­i­ty.

For spon­sors, the biggest sta­tis­ti­cal con­sid­er­a­tion is to ad­dress miss­ing in­for­ma­tion that aris­es from changes in study vis­it sched­ules, missed vis­its, or pa­tient dis­con­tin­u­a­tion due to COVID-19. The FDA guide­line in­di­cates spe­cif­ic in­for­ma­tion in the case re­port form (CRF) that ex­plains the ba­sis of how the miss­ing da­ta and the re­la­tion­ship to COVID-19 should be cap­tured and sum­ma­rized in the clin­i­cal study re­port to help the spon­sor and the FDA.

Main­tain­ing con­sis­ten­cy in as­sess­ment meth­ods should be bal­anced against the need to min­i­mize miss­ing da­ta and vari­abil­i­ty in the da­ta. The de­ci­sion to use dif­fer­ent meth­ods should be jus­ti­fied in study doc­u­men­ta­tion.

As a part of best prac­tices, Parex­el bio­sta­tis­ti­cians fol­low guide­lines to amend SAPs that may in­clude var­i­ous sen­si­tiv­i­ty analy­ses by an­a­lyz­ing pre vs. post COVID-19 da­ta sep­a­rate­ly.

The Im­por­tance of Cul­ture Map­ping

Be­fore COVID up­end­ed clin­i­cal tri­als all over the world, FSP out­sourc­ing was al­ready on the rise. The dis­cus­sion shift­ed to how to ac­cess the right tal­ent and main­tain project con­ti­nu­ity. Spon­sors of­ten strug­gle to find the right peo­ple – not on­ly with the right do­main ex­per­tise, but al­so to find tal­ent­ed peo­ple who can be quick­ly trained on their SOPs and al­so fit in­to their spe­cif­ic com­pa­ny’s cul­ture.

To find the best match, we use a method­ol­o­gy we call the Parex­el FSP Cul­ture Map™ process, de­signed to match both the skill set and the cul­tur­al fit of can­di­date to the bio­phar­ma cus­tomer. Honed by years of re­cruit­ment and place­ment ex­pe­ri­ence, it’s a method­ol­o­gy that looks be­yond a can­di­date’s pro­fes­sion­al skills and back­ground to eval­u­ate how their per­son­al­i­ty, adapt­abil­i­ty and soft skills will fit in a spe­cif­ic cus­tomer’s en­vi­ron­ment. In some cas­es, it can go down to the per­son­al­i­ty at the project lev­el. It may be im­por­tant to con­sid­er who the project lead is, or who the can­di­date may in­ter­act with the most. Find­ing the right tal­ent through cul­ture map­ping helps in­crease re­ten­tion and de­crease dis­rup­tion from staff turnover.

Staff re­ten­tion is ma­jor con­cern of any out­sourc­ing ini­tia­tive. Train­ing is a sig­nif­i­cant in­vest­ment and for many clin­i­cal roles it can take a full six months to en­sure staff mem­bers are pro­fi­cient in the cus­tomer sys­tems and process­es. A range of ini­tia­tives, from for­mal men­tor­ships, ca­reer de­vel­op­ment ap­proach­es and staff sup­port pro­grams pro­vide tan­gi­ble ex­am­ples of suc­cess­ful re­ten­tion ef­forts.

Look­ing for­ward, there are sev­er­al plau­si­ble lega­cies of COVID-19 on out­sourc­ing be­hav­ior. The glob­al trend of re­mote work­ing has proven suc­cess­ful in clin­i­cal tri­al man­age­ment and prod­uct life­cy­cle sup­port and will con­tin­ue to ac­cel­er­ate. As COVID-19 pro­vid­ed a dire re­minder of the pow­er of un­cer­tain­ty, more com­pre­hen­sive up­front plan­ning be­tween FSP providers and bio­phar­ma com­pa­nies is an­oth­er near-term pos­i­tive out­come. Fi­nal­ly, to­day’s un­pre­dictable en­vi­ron­ment re­quires new lev­els of nim­ble­ness from all stake­hold­ers to en­able bet­ter pre­pared­ness for any event. As more or­ga­ni­za­tions now have the lux­u­ry of time to look ahead, key ques­tions for spon­sors are whether they can ac­cess tar­get­ed re­sources and ex­per­tise and op­er­ate with ex­e­cu­tion choice and flex­i­bil­i­ty un­der new and ever-chang­ing cir­cum­stances.

For ad­di­tion­al in­sights, click here to watch a re­cent round­table dis­cus­sion on this top­ic.