Need a place­bo con­trol group for your next can­cer drug study? On­ly in cer­tain cir­cum­stances, says FDA

Giv­en the eth­i­cal chal­lenges of us­ing a place­bo in ran­dom­ized con­trolled clin­i­cal tri­als for ther­a­pies to treat hema­to­log­ic ma­lig­nan­cy and on­co­log­ic dis­ease, the FDA rec­om­mends that a spon­sor use a place­bo-con­trolled de­sign on­ly in se­lect cir­cum­stances, ac­cord­ing to new draft guid­ance re­leased Thurs­day.

Such cir­cum­stances in­clude “where sur­veil­lance is stan­dard of care,” or with spe­cif­ic tri­al “de­sign fea­tures (e.g. if the tri­al us­es an add-on de­sign, when the end­point in­tend­ed to sup­port a la­bel­ing claim has a high de­gree of sub­jec­tiv­i­ty, such as pa­tient re­port­ed out­comes).”

And when con­sid­er­ing the use of a place­bo con­trol, the FDA says spon­sors should pro­vide a ra­tio­nale for the tri­al de­sign and a de­tailed de­scrip­tion in the pro­to­col and sta­tis­ti­cal analy­sis plan of the pro­pos­al for blind­ing and un­blind­ing.

“If a spon­sor in­tends to main­tain the treat­ment blind when dis­ease re­curs or pro­gress­es or a sus­pect­ed ad­verse event oc­curs, the in­formed con­sent doc­u­ment should spec­i­fy the risks and po­ten­tial dis­ad­van­tages of this ap­proach, and the pro­to­col should in­clude jus­ti­fi­ca­tion for the po­ten­tial added risk,” the three-page draft says.

The FDA al­so rec­om­mends that spon­sors un­blind a pa­tient “at the time of doc­u­ment­ed dis­ease re­cur­rence or pro­gres­sion to en­sure op­ti­mal pa­tient man­age­ment.”

Con­tin­ued blind­ing at the time of dis­ease pro­gres­sion or oc­cur­rence of se­ri­ous ad­verse events presents ad­di­tion­al chal­lenges, the FDA says.

For ex­am­ple, in a blind­ed im­munother­a­py tri­al, a pa­tient who de­vel­ops ad­verse events on the con­trol arm may re­ceive un­nec­es­sary treat­ments (e.g., im­muno­sup­pres­sive drug prod­ucts in­clud­ing a high dose of glu­co­cor­ti­coids, cy­clophos­phamide, in­ter­leukin-6 an­tag­o­nist, or in­flix­imab) for man­age­ment of ad­verse events in­cor­rect­ly at­trib­uted to the in­ves­ti­ga­tion­al drug prod­uct.

Main­tain­ing the blind af­ter dis­ease pro­gres­sion could al­so af­fect a pa­tient’s sub­se­quent ther­a­py.

The FDA al­so rec­om­mends un­blind­ing the pa­tient and in­ves­ti­ga­tor “when the pa­tient has an ad­verse event sus­pect­ed to be re­lat­ed to the in­ves­ti­ga­tion­al drug prod­uct and for which man­age­ment of the ad­verse event with one or more drug prod­ucts with sub­stan­tial tox­i­c­i­ty or in­va­sive pro­ce­dures is be­ing con­sid­ered. In such cas­es of un­blind­ing, the pa­tient should not be re­moved from the tri­al.”

In terms of the prac­ti­cal and eth­i­cal con­cerns re­lat­ed to us­ing place­bos in some on­col­o­gy tri­als, the FDA notes that in many cas­es, be­cause of the tox­i­c­i­ty of the ac­tive treat­ment, pa­tients and in­ves­ti­ga­tors may know if they are re­ceiv­ing a place­bo 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.

Author

Zachary Brennan

managing editor, RAPS

John Hood [file photo]

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UP­DAT­ED: Sci­en­tist-CEO ac­cused of im­prop­er­ly us­ing con­fi­den­tial in­fo from uni­corn Alec­tor

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On June 18, 2019, we initiated a confidential arbitration proceeding against Dr. Asa Abeliovich, our former consulting co-founder, related to alleged breaches of his consulting agreement and the improper use of our confidential information that he learned during the course of rendering services to us as our consulting Chief Scientific Officer/Chief Innovation Officer. We are in the early stage of this arbitration proceeding and are unable to assess or provide any assurances regarding its possible outcome.

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