FDA fi­nal­izes guid­ance on adap­tive tri­al de­signs

The FDA last week fi­nal­ized guid­ance on adap­tive clin­i­cal tri­al de­signs for drugs and bi­o­log­ics.

The 33-page guid­ance, which fi­nal­izes a draft ver­sion re­leased for com­ment in Sep­tem­ber 2018 and re­places an ear­li­er guid­ance from 2010, sets out the FDA’s rec­om­men­da­tions on adap­tive tri­al de­sign prin­ci­ples and the in­for­ma­tion the FDA will re­view from adap­tive stud­ies sub­mit­ted as part of in­ves­ti­ga­tion­al new drug ap­pli­ca­tions (INDs), new drug ap­pli­ca­tions (NDAs), bi­o­log­ics li­cense ap­pli­ca­tions (BLAs) and sup­ple­men­tal ap­pli­ca­tions.

While the fi­nal guid­ance is large­ly the same as the draft ver­sion, the FDA says it has re­vised the guid­ance to clar­i­fy its rec­om­men­da­tions for Bayesian adap­tive de­signs and its ex­pec­ta­tions for the ex­tent of pre­spec­i­fi­ca­tion re­quired for gov­ern­ing adap­ta­tions to stud­ies in ad­di­tion to mi­nor ed­i­to­r­i­al changes.

The fi­nal guid­ance al­so refers spon­sors to re­view the FDA’s Sep­tem­ber 2019 draft guid­ance on com­plex in­no­v­a­tive tri­al de­signs for more in­for­ma­tion on tri­al de­sign pro­pos­als that use Bayesian in­fer­ence.

Ad­di­tion­al­ly, while the FDA rec­om­mends that spon­sors pre­spec­i­fy rules gov­ern­ing tri­al adap­ta­tions, the agency ac­knowl­edges that “mon­i­tor­ing com­mit­tee rec­om­men­da­tions might oc­ca­sion­al­ly de­vi­ate from the an­tic­i­pat­ed al­go­rithm based on the to­tal­i­ty of the da­ta.” The agency al­so says that if spon­sors de­sire flex­i­bil­i­ty ad­just­ing these de­vi­a­tions to their pre­spec­i­fied plan, they “should ac­knowl­edge the pos­si­bil­i­ty of de­vi­a­tions from the an­tic­i­pat­ed al­go­rithm, out­line fac­tors that may lead to such de­vi­a­tions, and pro­pose test­ing and es­ti­ma­tion meth­ods that do not re­ly on strict ad­her­ence to the al­go­rithm.”

In the Fed­er­al Reg­is­ter no­tice an­nounc­ing the fi­nal guid­ance, the FDA says it ex­pects to see ap­prox­i­mate­ly 240 doc­u­ment­ed plans for clin­i­cal tri­als with an adap­tive de­sign and analy­sis plan from 40 spon­sors an­nu­al­ly.

The FDA al­so says it ex­pects to re­ceive about 20 mar­ket­ing ap­pli­ca­tions for drugs and bi­o­log­ics from 15 spon­sors that re­ly on da­ta from an adap­tive study each year.


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Di­ag­nos­tic champ Roche buys its way in­to the RET ti­tle fight with Eli Lil­ly, pay­ing $775M in cash to Blue­print

When Roche spelled out its original $1 billion deal — $45 million of that upfront — with Blueprint to discover targeted therapies against immunokinases, the biotech partner’s RET program was still preclinical. Four years later, pralsetinib is on the cusp of potential approval and the Swiss pharma giant is putting in much more to get in on the commercial game.

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Trans­port Sim­u­la­tion Test­ing for Your Ther­a­py is the Best Way to As­sure FDA Ex­pe­dit­ed Pro­gram Ap­proval

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