The key to faster, more im­pact­ful re­search? Put pa­tients in the dri­ver’s seat

Pa­tient-dri­ven re­search is crit­i­cal for im­prov­ing out­comes in rare dis­eases.  Ev­i­dence from 5 years of fund­ing and sup­port­ing pa­tient-led or­ga­ni­za­tions shows why.

Most ma­jor bio­med­ical ad­vances are in­cre­men­tal, with drug de­vel­op­ment cost­ing hun­dreds of mil­lions and be­ing built on decades of foun­da­tion­al re­search. But it doesn’t have to take that long to de­liv­er im­pact, and many lives de­pend on ac­cel­er­at­ing this process. CZI’s Rare As One Net­work is an in­cu­ba­tor-style pro­gram with a re­pro­ducible mod­el that lever­ages the pow­er of pa­tients to achieve am­bi­tious sci­en­tif­ic goals.

Pa­tients are dis­tinct­ly mo­ti­vat­ed and pos­sess in­valu­able knowl­edge about the chal­lenges and op­por­tu­ni­ties with­in their con­di­tions. While a pa­tient-dri­ven re­search mod­el is im­por­tant for any dis­ease area, we’ve ap­plied it to rare dis­eases, where progress is stymied be­cause of the small pa­tient pop­u­la­tions in any giv­en dis­ease. Col­lec­tive­ly, rare dis­eases are any­thing but rare.  Over 400 mil­lion peo­ple glob­al­ly live with one of an es­ti­mat­ed 7,000-10,000 rare dis­eases, the vast ma­jor­i­ty of which are poor­ly un­der­stood. Un­for­tu­nate­ly, few­er than 5 per­cent of rare dis­eases have ap­proved treat­ments, and one-third of chil­dren with a rare dis­ease will die be­fore the age of 5. Rare dis­eases vary great­ly, but they are poised to ben­e­fit from many com­mon so­lu­tions, and bi­o­log­i­cal in­sights gleaned from a rare dis­ease of­ten ap­ply to com­mon dis­eases.

We fund­ed 30 pa­tient-led or­ga­ni­za­tions over three years to de­vel­op and/or ex­pand their re­search net­works, con­vene their com­mu­ni­ties, iden­ti­fy shared re­search pri­or­i­ties, and work to­geth­er as part of a learn­ing net­work. De­spite their small sizes, bud­gets, and ca­pac­i­ties, these or­ga­ni­za­tions far sur­passed our ex­pec­ta­tions.

When look­ing at the progress from our first fund­ed co­hort, three com­mon themes emerged that may ac­count for how this ap­proach over­comes typ­i­cal bar­ri­ers in sci­en­tif­ic re­search. Pa­tient com­mu­ni­ties can:

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1. Ad­vance foun­da­tion­al knowl­edge and bio­med­ical break­throughs
2. En­hance pa­tient rep­re­sen­ta­tion in re­search
3. Break down si­los and dri­ve col­lab­o­ra­tion

1. Ad­vance foun­da­tion­al knowl­edge and bio­med­ical break­throughs

Pa­tient-guid­ed part­ner­ships are high­ly pro­duc­tive at gen­er­at­ing new sci­en­tif­ic knowl­edge. In three years, the 30 grantees in our first fund­ing cy­cle en­gaged over 3,000 new re­searchers, pro­duc­ing over 182 pub­li­ca­tions. Along with these aca­d­e­m­ic out­puts, 25 out of 30 of the groups built clin­i­cal reg­istries and nat­ur­al his­to­ry stud­ies that are es­sen­tial as­sets for gen­er­at­ing fu­ture sci­en­tif­ic break­throughs.

Take, for ex­am­ple, TAN­GO2 de­fi­cien­cy dis­or­der—a rare dis­ease iden­ti­fied in 2018 and char­ac­ter­ized by de­vel­op­men­tal de­lay, in­tel­lec­tu­al dis­abil­i­ty, and re­cur­rent episodes of car­diac ar­rhyth­mias that can lead to se­vere meta­bol­ic crises. In 2019, the TAN­GO2 Re­search Foun­da­tion formed a col­lab­o­ra­tion with Bay­lor Col­lege of Med­i­cine and Texas Chil­dren’s Hos­pi­tal to launch a piv­otal nat­ur­al his­to­ry study to bet­ter un­der­stand the dis­ease.  Act­ing on ob­ser­va­tions from par­ents that their chil­dren’s symp­toms seemed to im­prove when tak­ing dai­ly mul­ti­vi­t­a­mins, the foun­da­tion en­sured da­ta were cap­tured to in­ves­ti­gate this pos­si­ble as­so­ci­a­tion. This led them to fund two ex­per­i­men­tal stud­ies that, just six years af­ter dis­ease dis­cov­ery, in 2022, ul­ti­mate­ly showed that vi­t­a­min B sup­ple­men­ta­tion could pre­vent fa­tal­i­ties re­lat­ed to TAN­GO2 de­fi­cien­cy-re­lat­ed meta­bol­ic crises. The re­sults of the stud­ies led a group of physi­cians to quick­ly pub­lish con­sen­sus guide­lines rec­om­mend­ing that all pa­tients with con­firmed TAN­GO2 de­fi­cien­cy take  dai­ly mul­ti­vi­t­a­min or B-com­plex sup­ple­ments. While not a cure, this crit­i­cal de­vel­op­ment has pro­vid­ed life-sav­ing im­prove­ments in pa­tient care and has set the stage for fur­ther break­throughs.

2. En­hance pa­tient rep­re­sen­ta­tion in re­search

Pa­tient di­ver­si­ty in re­search is of­ten lack­ing, de­spite be­ing vi­tal to ac­cu­rate­ly un­der­stand­ing the dis­ease and de­vel­op­ing treat­ments to serve all pa­tients. While more work still needs to be done, pa­tient or­ga­ni­za­tions are play­ing a crit­i­cal role in ad­dress­ing this gap and in work­ing to en­gage un­der­rep­re­sent­ed pop­u­la­tions.

The re­cruit­ment of rep­re­sen­ta­tive pa­tient pop­u­la­tions in­creas­es the like­li­hood that dif­fer­ences in drug me­tab­o­lism, side ef­fects, and out­comes will be caught ear­li­er in the re­search process, sav­ing time and re­sources, and en­sur­ing that treat­ments are ef­fec­tive for all. As lan­guage can be a ma­jor bar­ri­er to pa­tient re­cruit­ment and en­gage­ment, many RAO grantees are trans­lat­ing ma­te­ri­als for pa­tients and work­ing to en­sure that the voic­es of those im­pact­ed are rep­re­sent­ed.

For ex­am­ple, the Her­man­sky-Pud­lak Syn­drome (HPS) Net­work par­tic­i­pat­ed in a Pa­tient-Fo­cused Drug De­vel­op­ment (PFDD) meet­ing led by the FDA’s Cen­ter for Drug Eval­u­a­tion and Re­search where they worked to en­sure that the to­tal­i­ty of the pa­tient voice was rep­re­sent­ed and that all pa­tient ex­pe­ri­ences, needs, and pri­or­i­ties were mean­ing­ful­ly in­cor­po­rat­ed in­to drug de­vel­op­ment and eval­u­a­tion. Be­cause HPS oc­curs with a high­er fre­quen­cy in Puer­to Ri­co due to a founder ef­fect, the HPS Net­work en­gaged a large por­tion of the pop­u­la­tion in the meet­ing. To en­able par­tic­i­pa­tion, they pre-record­ed pa­tient in­put to mit­i­gate con­nec­tiv­i­ty is­sues on the is­land, trans­lat­ed the meet­ing in­to Span­ish—mak­ing it the first ever mul­ti-lin­gual PFDD—and then pub­lished a med­ical­ly trans­lat­ed Voice of the Pa­tient Re­port.

By in­ten­tion­al­ly cen­ter­ing pa­tient rep­re­sen­ta­tion, these or­ga­ni­za­tions sig­nif­i­cant­ly de-risk the de­vel­op­ment of new treat­ments, im­prove the over­all re­li­a­bil­i­ty of re­search, and en­sure all pa­tients im­pact­ed by the dis­ease can ben­e­fit.

3. Break down si­los and dri­ve col­lab­o­ra­tion

While we were con­fi­dent fund­ing pa­tient groups would lead to im­pact, we did not an­tic­i­pate the ex­tent to which our fund­ed co­hort would op­ti­mize shared learn­ings, re­sources and op­por­tu­ni­ties for col­lab­o­ra­tion.

As a re­sult of be­ing mem­bers of CZI’s RAO Net­work, grantees fo­cused on neu­ro­log­i­cal glyco­gen stor­age dis­or­ders— Glut1 De­fi­cien­cy Foun­da­tion, APBD Re­search Foun­da­tion, and Chelsea’s Hope—were able to con­nect. This kicked off a for­mal col­lab­o­ra­tion with a com­mon sci­ence ad­vi­sor to ex­plore sci­en­tif­ic syn­er­gies, in­creas­ing the pace of dis­cov­ery and re­sult­ing in a pub­li­ca­tion on emerg­ing ther­a­peu­tics in glyco­gen stor­age dis­eases, au­thored by rep­re­sen­ta­tives from two of the foun­da­tions and their ad­vi­sor.

The im­pact of the ‘net­work ef­fect’ was so pro­nounced that we de­cid­ed to specif­i­cal­ly em­pha­size syn­er­gies across chan­nelopathies, cil­iopathies, and in­her­it­ed meta­bol­ic dis­or­ders in our most re­cent fund­ing co­hort. With the ad­di­tion of 30 new grantees work­ing in these ar­eas, our Net­work is now near­ly 100 strong.

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The fu­ture of sci­en­tif­ic dis­cov­ery and erad­i­ca­tion of dis­ease is de­pen­dent on col­lab­o­ra­tion with pa­tients. Learn more about how pa­tient-led in­no­va­tion can dri­ve more ef­fi­cient, im­pact­ful and trans­la­tion­al bio­med­ical dis­cov­er­ies– and the val­ue of part­ner­ship with pa­tients to ac­cel­er­ate treat­ments and cures—in our im­pact re­port.