Good Clinical Trials by removing defensive interpretation of Good Clinical Practice guidelines

Jonas M. den Heijer, Jules A. A. C. Heuberger, Hemme Hijma, Annelieke C. Kruithof, Jeroen van Smeden, Geert Jan Groeneveld, Jacobus Burggraaf, Adam Cohen

The International Conference on Harmonization–Good Clinical Practice (ICH‐GCP) guidelines are implemented worldwide, to ensure the well‐being of trial participants and the quality of trials. However, we and others believe these guidelines are often defensively interpreted, contributing to the spiraling costs of trials and actually have a counterproductive effect on participant safety and trial integrity. These effects are unintended and the result of the complex environment in which trials are currently performed. Most trials have a multitude of stakeholders, some with commercial interests, others with scientific aims, and regulators and ethics committees. The results of many trials are used for market approval and therefore by itself have enormous stakes attached. The environment is risk‐averse, and this has led to increased regulation, but above all the most stringent interpretation of these rules. This has generated a market, where billion‐dollar contract research organizations (CROs) offer to provide support services to adhere to this defensive interpretation. The current best practice has made trials expensive and evaluation of older less commercially attractive treatments, for instance, the repurposing of existing treatments by others than pharmaceutical firms, difficult or impossible, with some notable exceptions like the Oxford Recovery trial that specifically states that they do not conform to the letter, but rather to the principles of GCP.

In this article, we share our investigations of the existing rules as applied to our context of a nonprofit clinical research unit connected to a major university medical centre, in which approximately 40–50 early phase studies in patients (50%) and healthy participants are performed per year ( We assessed the ICH‐GCP‐R2 guidelines point‐by‐point. Peculiarities from practice are primarily driven by a defensive interpretation of the chapters (4) Investigator, (5) Sponsor and (8) Essential documents. These peculiarities are shortly discussed per ICH‐GCP‐R2 chapter, and more importantly, suggestions are provided on how to interpret the guidelines more effectively. The original ICH‐GCP‐R2 text is cited. All suggestions aim to reduce redundant bureaucracy and improve both participant safety and a reliable trial. Many short examples are given in the Supporting Information, that may be relatable to other researchers, illustrative of the counterproductive current practice.

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