Pa­tients of­ten de­mand ex­per­i­men­tal drugs that prove in­ef­fec­tive — re­port

A new pa­per by a team of FDA of­fi­cials finds that on­ly about 30% of drugs re­quest­ed for ex­pand­ed ac­cess go on to be ap­proved by the agency.

“Ex­pand­ed ac­cess pro­vides just that: ac­cess. There is no guar­an­tee that the prod­uct sought will be ef­fec­tive and/or safe, much less that it will be ef­fec­tive and/or safe for the par­tic­u­lar pa­tient,” the au­thors write.

Back­ground

In re­cent years, the de­bate over pa­tient ac­cess to un­ap­proved drugs has risen to the na­tion­al stage. So called “right-to-try” laws, al­so known as right-to-ask laws, seek to by­pass FDA to pro­vide ac­cess to un­ap­proved drugs and have been en­act­ed in 37 states. In Au­gust, the US Sen­ate passed a bill that would ex­pand right-to-try na­tion­wide, though the House has yet to con­sid­er the bill.

The de­bate fo­cus­es on a pa­tient’s right to ac­cess un­ap­proved drugs to treat se­ri­ous or life-threat­en­ing dis­eases out­side of a clin­i­cal tri­al. Pro­po­nents of right-to-try have ar­gued that FDA is a bar­ri­er to pa­tient ac­cess, while FDA has coun­tered that it ap­proves near­ly all re­quests for ac­cess it re­ceives.

Un­der FDA’s ex­pand­ed ac­cess pro­gram, physi­cians can re­quest ac­cess to a drug for in­di­vid­ual pa­tients or a group of pa­tients un­der an ex­pand­ed ac­cess in­ves­ti­ga­tion­al new drug ap­pli­ca­tion (IND) or via a new pro­to­col un­der an ex­ist­ing IND.

While FDA main­tains that clin­i­cal tri­als are the best op­tion for pa­tients to get ac­cess to un­ap­proved drugs, the agency ac­knowl­edges that it’s not al­ways pos­si­ble for a pa­tient to en­roll in a clin­i­cal tri­al.

FDA has al­so said that in most cas­es phar­ma­ceu­ti­cal com­pa­nies de­ny re­quests for ex­pand­ed ac­cess, of­ten cit­ing sup­ply or safe­ty con­cerns. Right-to-try pro­po­nents have coun­tered that drug­mak­ers turn down such re­quests out of fear that ad­verse events that oc­cur be­cause of ex­pand­ed ac­cess use could de­rail their de­vel­op­ment pro­grams or open the com­pa­ny up to oth­er li­a­bil­i­ty is­sues.

Ex­pand­ed Ac­cess and Ap­proval

Ac­cord­ing to the au­thors, FDA re­ceived 6,054 unique ex­pand­ed ac­cess re­quests be­tween FY2010 and FY2014. Af­ter ex­clud­ing ex­pand­ed ac­cess re­quests for mul­ti­ple pa­tients and clean­ing the re­sults for du­pli­cate and “non­sub­mit­ted” INDs, the au­thors were left with 5,394 unique re­quests, 5,298 of which were al­lowed to pro­ceed.

Of those, the au­thors were able to iden­ti­fy 408 unique drugs and fixed-dose com­bi­na­tions.

By 30 Sep­tem­ber 2015, 122 (30%) of those drugs had been ap­proved by the agency for at least one in­di­ca­tion, though not nec­es­sar­i­ly for the in­di­ca­tions sought in ex­pand­ed ac­cess re­quests.

Six of the top ten most-re­quest­ed drugs went on to be ap­proved, though the pa­per does not men­tion the names of those drugs be­cause of con­fi­den­tial­i­ty rea­sons.

Look­ing at it from an­oth­er di­rec­tion, 3,365 of the 5,298 re­quests were for drugs that lat­er went on to be ap­proved, with a hand­ful of drugs ac­count­ing for a large pro­por­tion of those re­quests.

The au­thors al­so found lit­tle ev­i­dence to sup­port the ar­gu­ment that ad­verse events that oc­cur as a re­sult of ex­pand­ed ac­cess treat­ment can jeop­ar­dize a drug de­vel­op­ment pro­gram.

“Over the last decade, span­ning al­most 11,000 ex­pand­ed ac­cess re­quests, there were on­ly 2 in­stances in which a clin­i­cal hold was placed on com­mer­cial drug de­vel­op­ment due to ad­verse events oc­cur­ring un­der ex­pand­ed ac­cess. In both in­stances the de­vel­op­ment of the drugs con­tin­ued af­ter these is­sues were ad­dressed and the holds were lift­ed,” the au­thors write.

And the au­thors cast doubt on the ar­gu­ment that li­a­bil­i­ty con­cerns keep drug­mak­ers from pro­vid­ing ex­pand­ed ac­cess to their prod­ucts. A search of three le­gal data­bas­es, Google Schol­ar and HeinOn­line turned up no re­sults for prod­uct li­a­bil­i­ty suits against drug­mak­ers for per­son­al in­juries as a re­sult of ex­pand­ed ac­cess treat­ment.


First pub­lished here. Reg­u­la­to­ry Fo­cus is the flag­ship on­line pub­li­ca­tion of the Reg­u­la­to­ry Af­fairs Pro­fes­sion­als So­ci­ety (RAPS), the largest glob­al or­ga­ni­za­tion of and for those in­volved with the reg­u­la­tion of health­care and re­lat­ed prod­ucts, in­clud­ing med­ical de­vices, phar­ma­ceu­ti­cals, bi­o­log­ics and nu­tri­tion­al prod­ucts. Email news@raps.org for more in­for­ma­tion.

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