Communication of Nonefficacy Benefits of New Drugs Approved on the Basis of Noninferiority Trials Alone

Abstract

About one-third of new therapeutics are tested in head-tohead, active-controlled trials prior to licensure. 1 Some of these trials test noninferiority hypotheses, which by design allow for some potential loss of efficacy in exchange for potential nonefficacy benefits. The literature specifies several hypothetical nonefficacy benefits that new interventions approved based on noninferiority trials may offer, including decreased adverse events, less invasiveness, more convenient formulation, and reduced cost. 2-5 However, empirical evidence of actual b e n e f i t s i s l a c k i ng. We sought to characterize the nonefficacy benefits of new molecular entities (NMEs) approved based on noninferiority trials.

Noninferiority trials in clinical practice

“…Żywności i Leków (Food and Drug Administration -FDA) [20] podała wytyczne określające, kiedy projekt badania nie mniejszej skuteczności musi być zastosowany w celu ustalenia skuteczności nowego leku, zwykle dlatego że stosowanie placebo lub "brak leczenia" nie byłyby etyczne. Inne wytyczne dotyczące badań nie mniejszej skuteczności obejmują instrukcje dotyczące interwencji z bardziej korzystnymi profilami bezpieczeństwa lub wygodniejszym dawkowaniem, mniejszym obciążeniem pacjenta, mniejszymi kosztami lub innymi korzyściami, dla których pacjenci i klinicyści mogą zaakceptować zmniejszoną skuteczność jako kompromis [21].…”

Perspectives of US Adults on Antimicrobial Trials With Noninferiority Designs

“…New medical interventions are usually studied in trials evaluating improved efficacy vs current standards of care (superiority hypotheses). Increasingly, new medical interventions are studied using noninferiority (NI) hypotheses . It is statistically impossible to evaluate whether 2 interventions are identical; therefore, NI trials allow acceptable amounts of prechosen worse efficacy with new interventions compared with older, effective interventions, termed the NI margin , for patients with effective therapeutic options.…”

“…Increasingly, new medical interventions are studied using noninferiority (NI) hypotheses. 1 , 2 , 3 It is statistically impossible to evaluate whether 2 interventions are identical; therefore, NI trials allow acceptable amounts of prechosen worse efficacy with new interventions compared with older, effective interventions, termed the NI margin , for patients with effective therapeutic options. NI is ethical when potentially worse efficacy is traded off for other hypothesized advantages (nonefficacy benefits).…”

Communicating, and Justifying, Nonefficacy Benefits for New Drugs Approved on the Basis of Noninferiority Trials

“…In this issue of JAMA Internal Medicine , Doshi and colleagues bring attention to the FDA’s approval of new drugs on the basis of noninferiority-designed trials, which occurred among nearly 10% of approvals since 2011 . The authors examined how these nonefficacy benefits were communicated at the time of first approval through product sponsors’ (ie, pharmaceutical companies) and the FDA’s press releases and through the FDA’s Drug Trials Snapshots .…”