The nuances and scope of noninferiority trials

Abstract: Advancements in pharmacology and medicine have led to the establishment of the best efficacy drugs for most clinical conditions (standard of care) is already established; thus, the chance of emergence of newer drugs with exceeding efficacy is much less. But the new drugs developed may have other preferable features such as easy administration and lesser adverse effects. Noninferiority (NI) trials are designed to test whether the new drug’s diminished efficacy is within an acceptable limit, or not clinically, compared to the “standard of care” drug. If the new drug proves to be noninferior clinically, then it can become a preferred choice for the particular medical condition, provided the drug offers its other claimed benefits. NI trials are distinct from superiority and equivalence trials. Furthermore, a failed superiority trial/conventional parallel group trial cannot be used to claim equivalence or NI. One of the main reasons on choosing the NI design is that placebo cannot be used, as a standard of care drug is already available, and it would be unethical to deprive the trial participants. Most of the NI trials are performed in oncology, the cardiovascular system, and infectious diseases. NI trials have important concerns and specific issues regarding their design, conduct, and analysis like the choice of the active comparator and NI margin. NI trials make conclusions with confidence intervals instead of P values, and it is crucial to interpret them properly. NI trials should be carefully designed and carried out to avoid false conclusions of NI and accepting a drug with considerably less efficacy which is clinically unethical and hazardous. However, a well-designed and properly executed NI trial can discern alternative therapies with preferred attributes.