Com­pas­sion­ate Use/Ex­pand­ed Ac­cess pro­grams: Three steps to im­prove their im­ple­men­ta­tion for the ben­e­fit of all

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Com­pas­sion­ate Use or Ex­pand­ed Ac­cess is a treat­ment op­tion for pa­tients in des­per­ate need which can be in­de­pen­dent­ly re­quest­ed by a treat­ing physi­cian, pro­vid­ing ac­cess to lo­cal­ly un­li­censed med­ica­tions when all ap­proved treat­ment op­tions have been ex­haust­ed and en­roll­ment in a clin­i­cal tri­al is not pos­si­ble. There is no doubt about the hu­man val­ue of these pro­grams for pa­tients with no oth­er op­tion, and it’s al­so in­creas­ing­ly clear just how ben­e­fi­cial they can be for the en­tire health care ecosys­tem in ad­dress­ing the un­met med­ical needs of pa­tients. But many stake­hold­ers, from gov­ern­ments, health­care in­sti­tu­tions to phar­ma com­pa­nies, are not set up to make the best use of com­pas­sion­ate use. The time to change that is now.

I have been pas­sion­ate about com­pas­sion­ate use pro­grams for many years, but two re­cent events have crys­tal­lized their im­por­tance for me — in­di­cat­ing that we have reached a piv­otal mo­ment where the full po­ten­tial of these pro­grams is there for all to see, if the col­lec­tive will is there to grasp it.

First, in April, the FDA ap­proved a ther­a­py for a rare dis­ease based sole­ly on re­al-world da­ta ob­tained from pa­tients who were part of a com­pas­sion­ate use pro­gram. This was un­prece­dent­ed and shows just how cru­cial da­ta col­lec­tion in com­pas­sion­ate use has be­come to ac­cel­er­ate ap­proval of much-need­ed ther­a­pies, es­pe­cial­ly in rare dis­eases where there are of­ten none or very few treat­ment op­tions.

Sec­ond, my col­leagues and I in­ves­ti­gat­ed fac­tors as­so­ci­at­ed with com­pas­sion­ate use re­quests re­ceived at No­var­tis over a three-year pe­ri­od. The da­ta pub­lished in the Jour­nal of Amer­i­can Med­ical As­so­ci­a­tion (JA­MA) Health Fo­rum showed that of the 31,711 com­pas­sion­ate use re­quests from 110coun­tries, 87% were from high-in­come coun­tries. An even larg­er pro­por­tion – 94% – came from coun­tries with com­pas­sion­ate use reg­u­la­tions made pub­licly avail­able on the in­ter­net, and al­most all (96%) came from coun­tries with a high lev­el of clin­i­cal tri­al ac­tiv­i­ty. While these da­ta clear­ly re­veal vast dis­par­i­ties at the macro­eco­nom­ic lev­el, I be­lieve they al­so shine a light on the path for­ward — for gov­ern­ments, reg­u­la­tors and phar­ma alike.

As a phar­ma ex­ec­u­tive, I am most­ly fo­cused on what com­pa­nies can do to op­ti­mize their com­pas­sion­ate use pro­grams. I’ve been in­volved in this space for well over a decade, and the evo­lu­tion dur­ing this pe­ri­od has been phe­nom­e­nal. At No­var­tis alone, we now re­ceive on av­er­age about 10,000 re­quests every year, with an ap­proval rate of around 95%. We have gar­nered sig­nif­i­cant ex­pe­ri­ence and un­der­stand­ing over time, which we have used to push the bound­aries, pave the path for­ward and im­prove our pro­grams in the fol­low­ing ways:

Find the will be­fore the way

First, there must be a gen­uine de­sire to im­ple­ment and sup­port com­pas­sion­ate use pro­grams — and it must start at the top. Health­care com­pa­nies have a re­spon­si­bil­i­ty to en­able ac­cess to their in­no­v­a­tive med­i­cines to the pa­tients who need them most. At No­var­tis, we are com­mit­ted to help­ing en­sure that our med­i­cines are ac­ces­si­ble to as many pa­tients as pos­si­ble, ir­re­spec­tive of where they come from. We im­ple­ment com­pas­sion­ate use pro­grams be­cause it’s the right thing to do.

Ow­ing to the na­ture of the reg­u­la­to­ry and re­im­burse­ment process, there is of­ten a gap of sev­er­al months to years be­tween gen­er­a­tion of ro­bust ef­fi­ca­cy and safe­ty da­ta in tri­als and lo­cal mar­ket­ing au­tho­riza­tion with sub­se­quent lo­cal pa­tient ac­cess. Com­pas­sion­ate use pro­grams en­able the pro­vi­sion of cut­ting-edge ther­a­pies to those who des­per­ate­ly need them dur­ing this win­dow. For com­pa­nies, these pro­grams al­so pro­vide op­por­tu­ni­ties for the col­lec­tion of re­al-world da­ta from a broad­er pa­tient pop­u­la­tion be­yond the clin­i­cal tri­al, and an op­por­tu­ni­ty to en­gage with pa­tient com­mu­ni­ties, of­ten in­valu­able in rare dis­eases.

I be­lieve one of the main rea­sons for our high rate of com­pas­sion­ate use ap­provals is be­cause there’s an un­der­pin­ning phi­los­o­phy where the de­fault is to say ‘yes’, un­less there’s a jus­ti­fied med­ical or sci­en­tif­ic ra­tio­nale not to. Hav­ing this pa­tient-cen­tric mind­set in place and the will­ing­ness to de­ploy re­sources in this area is es­sen­tial.

In­still a ro­bust com­pa­ny pol­i­cy en­abled by an end-to-end re­quest sys­tem

A com­mit­ment to com­pas­sion­ate use means hav­ing the poli­cies, end-to-end process­es, and sys­tems in place to man­age re­quests in a prompt, fair and ef­fi­cient man­ner. The US 21st Cen­tu­ry Cures Act has since 2017 re­quired that phar­ma com­pa­nies de­vel­op­ing in­ves­ti­ga­tion­al drugs (in­clud­ing bi­o­log­ics) make their poli­cies re­gard­ing eval­u­at­ing and re­spond­ing to re­quests read­i­ly and pub­licly avail­able, e.g. on com­pa­ny web­sites.

A cen­tral­ized pol­i­cy and gov­er­nance pro­vide a sol­id foun­da­tion. We have a ded­i­cat­ed group in place act­ing as a Cen­ter of Ex­cel­lence, which has holis­tic over­sight and en­sures all el­e­ments are in place. This al­so in­cludes in­cor­po­rat­ing ad­e­quate guardrails in­to the process, the han­dling of ex­cep­tions, ad­dress­ing ini­tial pe­di­atric use and dos­ing ques­tions (e.g. man­aged with our in­te­grat­ed safe­ty as­sess­ment board), and the use of an ex­ter­nal in­de­pen­dent bioethics ad­vi­so­ry com­mit­tee (IBAC) for se­lect­ed eth­i­cal chal­lenges re­lat­ed to com­pas­sion­ate use.

With the in­creas­ing use of ge­net­ic test­ing and evo­lu­tion of tar­get­ed ther­a­pies, it is im­por­tant to con­sid­er how in­di­vid­ual pa­tient re­quests will be han­dled, es­pe­cial­ly for in­di­ca­tions where the com­pa­ny has no ac­tive or on­go­ing de­vel­op­ment pro­gram.

It’s al­so es­sen­tial to build a user-friend­ly com­pas­sion­ate use re­quest sys­tem — any dif­fi­cul­ties ac­cess­ing or us­ing the sys­tem, or lim­i­ta­tions to who can use it, are like­ly to de­ter treat­ing physi­cians and hin­der the re­ceipt of re­quests.

We launched an on­line re­quest sys­tem in De­cem­ber 2019 to stream­line re­quest man­age­ment. It’s sim­ple and can be used by physi­cians any­where in the world. Treat­ing physi­cians can sub­mit and han­dle a re­quest through any desk­top or mo­bile de­vice. In gen­er­al, it en­ables a speedy turn­around time — most re­view out­comes are pro­vid­ed with­in five work­ing days, en­sur­ing the pa­tient and treat­ing physi­cian do not lose a lot of time.

Part­ner with oth­ers and share your find­ings

We be­lieve open­ness and part­ner­ships are vi­tal pieces of the puz­zle. The da­ta from our JA­MA analy­sis was lim­it­ed to the ex­pe­ri­ence of a sin­gle com­pa­ny, and re­sults may dif­fer across oth­er or­ga­ni­za­tions. In light of this, we would wel­come sim­i­lar da­ta analy­sis from our in­dus­try peers and reg­u­la­tors to help in­form and en­rich the over­all knowl­edge base in this space.

There are on­go­ing best-prac­tice col­lab­o­ra­tions be­tween mul­ti­ple stake­hold­ers — in­clud­ing phar­ma com­pa­nies, pa­tient groups, reg­u­la­tors, gov­ern­ments, health­care pro­fes­sion­als, ven­dors and acad­e­mia — to en­sure that pa­tient ac­cess needs in com­pas­sion­ate use are ad­dressed holis­ti­cal­ly. It is im­por­tant to be a part of these con­ver­sa­tions and col­lab­o­ra­tions to en­sure di­verse per­spec­tives and ex­pe­ri­ences are con­sid­ered in the de­vel­op­ment of so­lu­tions to help ad­dress pa­tient ac­cess needs glob­al­ly.

There has been so much progress al­ready, but there’s still a lot that could be done to im­prove the im­ple­men­ta­tion of com­pas­sion­ate use pro­grams around the world. The best way for­ward is to­geth­er, for the ul­ti­mate ben­e­fit of pa­tients.

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