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Looking for safety but overlooking efficacy: Non-inferiority trials of anti-diabetics

      Testing new interventions against placebo when effective treatments are already available is considered unethical [
      • World Medical Association
      The Declaration of Helsinki.
      ] and dangerous for patients [
      • Garattini S.
      • Bertele' V.
      • Banzi R.
      Placebo? No thanks, it might be bad for me!.
      ], so testing non-inferiority which aims at demonstrating that a new intervention is not unacceptably worse than standard clinical practice should be equally unethical [
      • Garattini S.
      • Bertele' V.
      Non-inferiority trials are unethical because they disregard patients' interests.
      ,
      • Bertele' V.
      • Banzi R.
      • Gluud C.
      • Garattini S.
      EMA's reflection on placebo does not reflect patients' interests.
      ]. The understanding is that part of the benefit can be given up in exchange for less important advantages – such as better tolerability, convenience, etc. – which are claimed though often not proved. Going one step further, i.e. exploring even whether a treatment is non-inferior to placebo – meaning not unacceptably worse than doing nothing - should be inconceivable from both the ethical and the clinical points of view. Nevertheless, the approach has gained ground, for example in the area of diabetes.

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