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Phase IV research: innovation in need of ethics
  1. Ghislaine J M W van Thiel,
  2. Johannes J M van Delden
  1. University Medical Center Utrecht
    Julius Center for Health Sciences and Primary Care, Utrecht, The Netherlands
  1. Ghislaine van Thiel, University Medical Center Utrecht, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlands; g.j.m.w.vanthiel{at}umcutrecht.nl

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Worries about safety of approved drugs have pushed post registration research (phase IV) to become the fastest growing drug research phase. Until recently, phase IV studies were mainly conducted for marketing purposes and run much like a phase III trial—at institutions with experienced investigators and a list of inclusion and exclusion criteria. Innovative phase IV studies involve ordinary physicians in research naïve communities. This brings ethical issues familiar to medical research into clinical practice. As a consequence, individual physicians are challenged to protect scientific integrity and to secure the ethical conduct of research. Several ethical issues need to be addressed in the process of developing a scientifically sound and ethically high principled practice of phase IV research.

PHASE IV

Essential to phase IV research is the focus on how drugs work in the real world. The research goal may be to explore a specific pharmacological effect, to establish the incidence of adverse reactions, or to determine the effects of long-term administration of a drug. They may also be designed to establish a new clinical indication for a drug.1 Subjects may or may not be randomised, and the studies typically involve large numbers of patient-subjects and physicians.

Doubts concerning the scientific rigor and clinical value have put postmarketing research in a poor light. However, high quality phase IV research is badly needed to further pharmaceutical science. First, because it can provide reliable data on the effectiveness, safety and optimal use of a drug in treated populations.2 3 In pre-registration clinical trials (phase I–III), a pharmaceutical product is studied under unrealistic circumstances. Under-representation of women and elderly are common and the concomitant use of medicines is usually extremely restrictive in these trials.4 Second, phase IV can provide much needed data for evidence-based …

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