State of the art in benefit-risk analysis: medicines.

Benefit-risk assessment in medicine has been a valuable tool in the regulation of medicines since the 1960s. Benefit-risk assessment takes place in multiple stages during a medicine's life-cycle and can be conducted in a variety of ways, using methods ranging from qualitative to quantitative. Each benefit-risk assessment method is subject to its own specific strengths and limitations. Despite its widespread and long-time use, benefit-risk assessment in medicine is subject to debate and suffers from a number of limitations and is currently still under development. This state of the art review paper will discuss the various aspects and approaches to benefit-risk assessment in medicine in a chronological pathway. The review will discuss all types of benefit-risk assessment a medicinal product will undergo during its lifecycle, from Phase I clinical trials to post-marketing surveillance and health technology assessment for inclusion in public formularies. The benefit-risk profile of a drug is dynamic and differs for different indications and patient groups. In the end of this review we conclude benefit-risk analysis in medicine is a developed practice that is subject to continuous improvement and modernisation. Improvement not only in methodology, but also in cooperation between organizations can improve benefit-risk assessment.

[1]  Jing Jing Li,et al.  Using effectiveness and cost-effectiveness to make drug coverage decisions: a comparison of Britain, Australia, and Canada. , 2009, JAMA.

[2]  K. Alexander,et al.  Representation of elderly persons and women in published randomized trials of acute coronary syndromes. , 2001, JAMA.

[3]  M. Drummond,et al.  Key principles for the improved conduct of health technology assessments for resource allocation decisions , 2008, International Journal of Technology Assessment in Health Care.

[4]  A. Fourrier-Réglat,et al.  The EU-ADR project: preliminary results and perspective. , 2009, Studies in health technology and informatics.

[5]  Nancy J Devlin,et al.  "Yes", "No" or "Yes, but"? Multinomial modelling of NICE decision-making. , 2006, Health policy.

[6]  J Raftery,et al.  NICE: faster access to modern treatments? Analysis of guidance on health technologies , 2001, BMJ : British Medical Journal.

[7]  B. Djulbegovic,et al.  Pharmaceutical industry sponsorship and research outcome and quality: systematic review , 2003, BMJ : British Medical Journal.

[8]  A. Gafni,et al.  Economists’ dream or nightmare? Maximizing health gains from available resources using the NICE guidelines , 2007, Health Economics, Policy and Law.

[9]  T. Fleming,et al.  Surrogate end points, health outcomes, and the drug-approval process for the treatment of risk factors for cardiovascular disease. , 1999, JAMA.

[10]  Zhengwu Lu,et al.  Technical challenges in designing post-marketing eCRFs to address clinical safety and pharmacovigilance needs. , 2010, Contemporary clinical trials.

[11]  Jerry Avorn,et al.  Evaluating drug effects in the post-Vioxx world: there must be a better way. , 2006, Circulation.

[12]  I. Edwards,et al.  Adverse drug reactions: definitions, diagnosis, and management , 2000, The Lancet.

[13]  J. Botting.  The History of Thalidomide. , 2002, Drug news & perspectives.

[14]  Robert H. Brook,et al.  Efficacy, Effectiveness, Variations, and Quality , 1991 .

[15]  B. Bégaud,et al.  Improving pharmacovigilance in Europe , 2010, BMJ : British Medical Journal.

[16]  P. Honig.  Benefit and Risk Assessment in Drug Development and Utilization: A Role for Clinical Pharmacology , 2007, Clinical pharmacology and therapeutics.

[17]  L Liberti,et al.  Measuring Benefit and Balancing Risk: Strategies for the Benefit–Risk Assessment of New Medicines in a Risk‐Averse Environment , 2009, Clinical pharmacology and therapeutics.

[18]  John Doyle,et al.  A review of quantitative risk-benefit methodologies for assessing drug safety and efficacy-report of the ISPOR risk-benefit management working group. , 2010, Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research.

[19]  Z. Bankowski,et al.  Council for International Organizations of Medical Sciences , 1991 .

[20]  L. Garrison.  Regulatory Benefit-Risk Assessment and Comparative Effectiveness Research , 2012, PharmacoEconomics.

[21]  Steven Pearson,et al.  Relative efficacy of drugs: an emerging issue between regulatory agencies and third-party payers , 2010, Nature Reviews Drug Discovery.

[22]  S. Feldman,et al.  What Is the Best Approach to Reducing Birth Defects Associated with Isotretinoin? , 2006, PLoS medicine.

[23]  M. Egger,et al.  Risk of cardiovascular events and rofecoxib: cumulative meta-analysis , 2004, The Lancet.

[24]  Louis P Garrison,et al.  Assessing a structured, quantitative health outcomes approach to drug risk-benefit analysis. , 2007, Health affairs.