De-risk­ing the pa­tient jour­ney in cell ther­a­pies: Six key con­sid­er­a­tions

Suc­cess­ful­ly com­plet­ing a cell ther­a­py pro­gram (CAR T, TCR, TIL or oth­er cell con­structs) isn’t with­out in­her­ent risks or un­ex­pect­ed de­lays. The pa­tient’s needs, the physi­cian’s guid­ance, health­care lim­i­ta­tions and lo­gis­ti­cal chal­lenges are on­ly a few of the fac­tors that need to be con­sid­ered. At any step, from vein to vein, uniden­ti­fied risks or unan­tic­i­pat­ed time de­lays can sig­nif­i­cant­ly im­pact the pa­tient’s clin­i­cal jour­ney. To run a time­ly and hur­dle-free cell ther­a­py pro­gram, de-risk­ing strate­gies need to be built in­to the ac­tion plan.

From pa­tient screen­ing, through cell prod­uct in­fu­sion and to long-term fol­low-up, the pa­tient jour­ney has nu­mer­ous risks that can de­rail clin­i­cal progress. As Fortrea is com­mit­ted to fa­cil­i­tat­ing the best pos­si­ble clin­i­cal out­comes, years of sup­port­ing and de­sign­ing dozens of cell ther­a­py pro­grams, in­clud­ing all 6 FDA-ap­proved CAR T-cell ther­a­pies, have led to our iden­ti­fi­ca­tion of six risk nodes along the pa­tient jour­ney. In this pa­per, we present these six risk nodes, as well as de­scribe ac­tion­able mea­sures de­signed to mit­i­gate each of these risks.

6 risk nodes

In this pa­per, we present these six risk nodes, as well as de­scribe ac­tion­able mea­sures de­signed to mit­i­gate each of these risks.

Risk 1: Lim­it­ed ac­cess to clin­i­cal tri­als

How we ad­dress this:
Mak­ing clin­i­cal tri­al par­tic­i­pa­tion more ac­ces­si­ble to all pa­tients is one of our pri­ma­ry goals. By part­ner­ing with the Spon­sor, we make tri­als avail­able and vis­i­ble to po­ten­tial pa­tients in coun­tries par­tic­i­pat­ing in the tri­al but al­so out­side coun­tries in­volved. To im­prove tri­al vis­i­bil­i­ty and en­cour­age par­tic­i­pa­tion, we’ve part­nered with di­rect-to-pa­tient sup­port or­ga­ni­za­tions and pa­tient ad­vo­ca­cy groups. Through these ef­forts, we’re able to high­light clin­i­cal tri­al op­por­tu­ni­ties to pa­tients al­ready di­ag­nosed with the dis­ease of in­ter­est as well as ed­u­cate them on op­tions for bet­ter clin­i­cal out­comes.

Fortrea ex­perts are al­ways keen to part­ner with a Spon­sor and de­sign the tri­al pro­to­col, tak­ing in­to ac­count the voice of the pa­tient and pri­or­i­tiz­ing the pa­tient’s well-be­ing and health. Avail­able da­ta on pa­tient pref­er­ences and the needs of their care­givers are tak­en in­to ac­count to min­i­mize pa­tient bur­den. To make par­tic­i­pa­tion eas­i­er dur­ing the tri­al, we aim to of­fer de­cen­tral­ized tri­al sup­port through tech­nol­o­gy-en­abled so­lu­tions where pos­si­ble.

Ad­di­tion­al­ly, we part­ner with lead­ing es­tab­lished can­cer cen­ters with proven ex­per­tise in cell ther­a­pies to en­sure that clin­i­cal tri­als are apt­ly placed at sites equipped with the ca­pa­bil­i­ties and clin­i­cal know-how to pro­vide every pa­tient with a safe and stress-free ex­pe­ri­ence.

Risk 2: Strin­gent pa­tient el­i­gi­bil­i­ty cri­te­ria and pro­to­col bar­ri­ers

How we ad­dress this:
Pa­tient el­i­gi­bil­i­ty cri­te­ria has a di­rect im­pact on pa­tient en­roll­ment. Get­ting the bal­ance right on how strin­gent en­roll­ment needs to be re­quires care­ful at­ten­tion to its de­sign – too strin­gent, and en­roll­ment is im­pact­ed; too le­nient and reg­u­la­to­ry re­quire­ments are not like­ly to be met. Based on the needs of the spon­sor, our team of med­ical con­sul­tants and ex­pe­ri­enced pro­to­col writ­ers can de­sign pro­to­cols with fea­si­ble pa­tient en­roll­ment cri­te­ria while ful­ly up­hold­ing reg­u­la­to­ry re­quire­ments and goals of the tri­al.

While Fortrea’s ex­pert team al­ways tries to be in­volved in pro­to­col de­sign and fi­nal­iza­tion, we re­view in­clu­sion-ex­clu­sion cri­te­ria and iden­ti­fy po­ten­tial en­roll­ment bar­ri­ers, such as mol­e­c­u­lar geno­typ­ing, screen­ing for spe­cif­ic tu­mor-as­so­ci­at­ed anti­gens or pa­tient age re­stric­tions. We al­so care­ful­ly ex­am­ine the pro­to­col lan­guage as this can po­ten­tial­ly pose re­stric­tions or ex­pand time­lines, for ex­am­ple, lim­it­ing where lab tests can be per­formed. Adding el­e­ments of flex­i­bil­i­ty to clin­i­cal tri­al pro­to­cols be­fore fi­nal­iz­ing them elim­i­nates ar­ti­fi­cial­ly im­posed bar­ri­ers, re­duces num­ber of pro­to­col de­vi­a­tions and sig­nif­i­cant­ly im­proves pa­tient en­roll­ment and pa­tient tri­al ex­pe­ri­ence.

Be­fore a tri­al be­gins, we en­sure that the site is ready and ful­ly set up to ex­e­cute the cell ther­a­py clin­i­cal tri­al pro­to­col. Dur­ing the tri­al, we as­sist sites with op­er­a­tional­iz­ing these pro­to­cols most op­ti­mal­ly, of­ten pro­vid­ing guid­ance to help mit­i­gate risks or de­lays. All mem­bers of the mul­ti­dis­ci­pli­nary site team are trained in tri­al pro­ce­dures, the apheretic cen­ter is prop­er­ly qual­i­fied, and cell ther­a­py lo­gis­tic path­way is es­tab­lished and val­i­dat­ed by the Fortrea team.

Ad­di­tion­al­ly, our med­ical team is close­ly in­volved in pro­duc­ing ed­u­ca­tion­al ma­te­ri­als to pro­vide pa­tients and their fam­i­lies/care­givers with up-to-date in­for­ma­tion re­gard­ing the tri­al process, time­lines, and po­ten­tial side ef­fects and com­pli­ca­tions. These in­for­ma­tion sheets and videos are made avail­able to the pa­tients along with the in­formed con­sent forms.

Risk 3: De­lays with clin­i­cal pro­ce­dures (such as aphere­sis)

How we ad­dress this:
Once pa­tients are iden­ti­fied at the clin­i­cal tri­al sites, an ac­tive dis­cus­sion be­tween the site, the spon­sor and the Fortrea clin­i­cal team be­gins. De­tails re­gard­ing the pa­tient’s cur­rent sta­tus and avail­abil­i­ty, screen­ing, progress with sign­ing con­sent forms, tim­ing of tri­al pro­ce­dures such as cell col­lec­tion and so on are tracked and re­port­ed to the spon­sor’s teams some­times in re­al time in­stead of week­ly meet­ings. Ques­tions aris­ing at the tri­al site re­gard­ing pa­tient as­sess­ment or pro­ce­dure sched­ul­ing are prompt­ly an­swered by Fortrea’s med­ical mon­i­tor and clin­i­cal team.

We en­sure that flex­i­bil­i­ties avail­able in the pro­to­col are ful­ly ex­er­cised to get the pa­tients through the process with­out un­nec­es­sary de­lays and bar­ri­ers. If un­ex­pect­ed de­lays are an­tic­i­pat­ed, the ded­i­cat­ed Fortrea team im­me­di­ate­ly no­ti­fies the spon­sor so con­tin­gency plans can be ex­e­cut­ed to ad­dress risks and en­sure the pa­tient can be suc­cess­ful­ly treat­ed. Mean­while, the at­tend­ing physi­cian man­ages the pa­tient’s health so el­i­gi­bil­i­ty cri­te­ria can still be main­tained.

Risk 4: De­lays with man­u­fac­tur­ing and ar­rival of cell ther­a­py

How we ad­dress this:
Our Fortrea lo­gis­tics co­or­di­na­tor re­mains in reg­u­lar con­tact with the man­u­fac­tur­er and lo­gis­tic ven­dors, re­ceiv­ing up­dates on sched­ules, back­logs or de­lays. In ad­di­tion to the per­son­al com­mu­ni­ca­tion by the co­or­di­na­tor, our part­ner­ship with Trak­Cel of­fers a tech­no­log­i­cal ad­van­tage in stay­ing up­dat­ed. Every pack­age hold­ing the pa­tient’s cells is geo-tagged and tracked through the ship­ping and man­u­fac­tur­ing cy­cles, its sta­tus up­dat­ing every 15 sec­onds.

If de­lays are no­ticed or qual­i­ty con­cerns be­come ap­par­ent, the spon­sors and the clin­i­cal sites are im­me­di­ate­ly no­ti­fied so that physi­cians can start dis­cussing pos­si­ble bridg­ing ther­a­pies, as al­lowed by the tri­al pro­to­col, for pa­tients be­fore cell ther­a­py prod­uct be­comes ready for in­fu­sion.

As we sup­port on­go­ing cell ther­a­py clin­i­cal tri­als, we’re al­so gath­er­ing re­al-world ev­i­dence about qual­i­ty at­trib­ut­es and op­ti­mum lo­gis­ti­cal prac­tices so we’re con­tin­u­al­ly able to of­fer rec­om­men­da­tions to re­fine man­u­fac­tur­ing process­es.

Risk 5: Com­pli­ca­tions re­lat­ed to cell ad­min­is­tra­tion and tox­i­c­i­ties

How we ad­dress this:
We se­lect sites and prin­ci­pal in­ves­ti­ga­tors with field ex­pe­ri­ence in ad­min­is­ter­ing cell ther­a­pies. Fa­mil­iar­i­ty with cell ther­a­pies and po­ten­tial com­pli­ca­tions makes ob­serv­ing and man­ag­ing ad­verse events more re­li­able.

Pa­tients are made aware of po­ten­tial com­pli­ca­tions such as cy­tokine re­lease syn­drome (CRS), neu­ro­tox­i­c­i­ty and in­fec­tions through ed­u­ca­tion­al ma­te­ri­als pro­vid­ed dur­ing in­formed con­sent. Ad­di­tion­al­ly, to sup­port tri­al sites, we can al­so pro­vide guid­ance to mon­i­tor, re­port and man­age pos­si­ble side ef­fects or health com­pli­ca­tions. Many pro­to­cols of­fer spe­cif­ic treat­ment al­go­rithms for com­mon­ly ob­served side ef­fects, along with cri­te­ria for ad­min­is­ter­ing stan­dard med­ica­tions to man­age them.

Ad­di­tion­al­ly, be­fore the start of a clin­i­cal tri­al, our team en­sures that clin­i­cal sites have the nec­es­sary sup­ply of med­ica­tions stocked in their phar­ma­cy to im­me­di­ate­ly man­age pa­tient com­pli­ca­tions. If nec­es­sary, we al­so pro­vide rec­om­men­da­tions for al­ter­na­tive sources of med­ica­tions so there are no short­ages or de­lays.

Risk 6: Sus­tained par­tic­i­pa­tion in long-term fol­low-up

How we ad­dress this:
Due to the rel­a­tive nov­el­ty of cell ther­a­pies, long-term fol­low-up process­es may not nec­es­sar­i­ly have gold stan­dard prac­tices. How­ev­er, through our ex­pe­ri­ence, we’re able to ob­serve strate­gies that boost pa­tient com­pli­ance and can make rec­om­men­da­tions to spon­sors based on cur­rent or past best prac­tices that have been suc­cess­ful.

Through tele-vis­its that pro­vide vir­tu­al health mon­i­tor­ing or through our mo­bile clin­i­cal ser­vices, where nurs­es or physi­cians go to a pa­tient’s home to mon­i­tor health and col­lect sam­ples, we aim to min­i­mize pa­tient bur­den and costs as­so­ci­at­ed with long-term fol­low-ups, there­by hop­ing to im­prove sus­tained par­tic­i­pa­tion. We’re al­so able to lo­cal­ize pa­tient sam­ple test­ing by tap­ping in­to our glob­al net­work of clin­i­cal lab­o­ra­to­ries. Fortrea’s so­lu­tion en­sures the key da­ta such as per­sis­tence of cells in­fused or de­layed ad­verse events re­lat­ed to cell/gene ther­a­py are col­lect­ed dur­ing the long-term fol­low-up part of the tri­al.

Fi­nal­ly, to pave the path for fu­ture cell ther­a­py pro­grams, we’re con­tin­u­al­ly en­gaged in di­a­logue with reg­u­la­to­ry bod­ies to de­vel­op well-de­fined strate­gies that can sup­port the suc­cess of ex­tend­ed long-term fol­low-ups.


At Fortrea, we val­ue the per­spec­tives of the dif­fer­ent stake­hold­ers in­volved in ad­min­is­ter­ing cell ther­a­pies, plac­ing the pa­tient ex­pe­ri­ence at the high­est pri­or­i­ty. We un­der­stand how spon­sors and clin­i­cal tri­al sites need to have de-risk­ing mea­sures in place so that pa­tients don’t need to wait any longer to re­ceive life-chang­ing ther­a­pies. Hav­ing seen the cell ther­a­py field evolve and hav­ing had the op­por­tu­ni­ty to play a sig­nif­i­cant role in its de­vel­op­ment by sup­port­ing all 6 FDA-ap­proved CAR T-cell ther­a­pies, we’re able to iden­ti­fy, an­tic­i­pate and even take pre­emp­tive steps to min­i­mize risks.

Reach out to our cell and gene ther­a­py team to start a con­ver­sa­tion about how we can of­fer sup­port to de-risk and ac­cel­er­ate your pro­gram.

About Fortrea

Fortrea is a lead­ing glob­al provider of clin­i­cal de­vel­op­ment and pa­tient ac­cess so­lu­tions to the life sci­ences in­dus­try. We part­ner with emerg­ing and large bio­phar­ma­ceu­ti­cal, biotech­nol­o­gy, med­ical de­vice and di­ag­nos­tic com­pa­nies to dri­ve health­care in­no­va­tion that ac­cel­er­ates life-chang­ing ther­a­pies to pa­tients. Fortrea pro­vides phase I-IV clin­i­cal tri­al man­age­ment, clin­i­cal phar­ma­col­o­gy, con­sult­ing ser­vices, dif­fer­en­ti­at­ed tech­nol­o­gy en­abled tri­al so­lu­tions and post-ap­proval ser­vices.

Fortrea’s so­lu­tions lever­age three decades of ex­pe­ri­ence span­ning more than 20 ther­a­peu­tic ar­eas, a pas­sion for sci­en­tif­ic rig­or, ex­cep­tion­al in­sights and a strong in­ves­ti­ga­tor site net­work. Our tal­ent­ed and di­verse team work­ing in more than 90 coun­tries is scaled to de­liv­er fo­cused and ag­ile so­lu­tions to cus­tomers glob­al­ly.