1. Presentation based on Turner, J.R., New Drug Development, and Turner, J.R., Drug Cardiac Safety. Copyright © 2007, 2008 respectively, John Wiley & Sons, Inc., All Rights Reserved. Presentation to FDA Advisory Committees July 30 th 2007 J. Rick Turner, PhD Chairman and Associate Professor, Department of Clinical Research Campbell University School of Pharmacy and President, Turner Medical Communications LLC Views expressed are those of the author and Turner Medical Communications LLC and not necessarily those of Campbell University.

2. Presentation based on Turner, J.R., New Drug Development, and Turner, J.R., Drug Cardiac Safety. Copyright © 2007, 2008 respectively, John Wiley & Sons, Inc., All Rights Reserved. The Benefit-risk Balance No drug is immune from possibility of unwanted responses, and a drug’s safety profile must therefore be evaluated in conjunction with its efficacy/effectiveness. Benefit-risk assessments are critical components of: Regulatory decisions affecting many patients. Clinical decisions affecting individual patients.

3. Presentation based on Turner, J.R., New Drug Development, and Turner, J.R., Drug Cardiac Safety. Copyright © 2007, 2008 respectively, John Wiley & Sons, Inc., All Rights Reserved. Inman and Weber (1986) “Risk-benefit judgements are complex…Irresponsible reporting by the lay press frequently leads to political pressure to restrict or ban drugs…The continued use of many valuable drugs must depend on the ability of the monitoring and regulatory agency to withstand criticism. Their policy on the whole is to warn about dangers rather than ban drugs because of them.” Inman, W.H.W. and Weber, J.C.P, 1986, The United Kingdom. In Inman, W.H.W. (Ed), Monitoring for Drug Safety, 2 nd Edition. Lancaster, UK: MTP Press/Kluwer Academic Publishers Group, p. 39. (13-47)

4. Presentation based on Turner, J.R., New Drug Development, and Turner, J.R., Drug Cardiac Safety. Copyright © 2007, 2008 respectively, John Wiley & Sons, Inc., All Rights Reserved. FDA Guidance for Industry: RiskMAPs (2005) “ FDA views risk management as an iterative process encompassing the assessment of risks and benefits, the minimization of risks, and the maximization of benefits.” FDA Guidance for Industry, March 2005: Development and Use of Risk Minimization Action Plans.

5. Presentation based on Turner, J.R., New Drug Development, and Turner, J.R., Drug Cardiac Safety. Copyright © 2007, 2008 respectively, John Wiley & Sons, Inc., All Rights Reserved. Institute of Medicine (2007) “The role of the regulator is not to impede the development of innovative medicines, but to ensure that needed drugs are available to patients and that risk-benefit information is accurate and widely available.” Institute of Medicine of the National Academies, 2007, The Future of Drug Safety: Protecting and Promoting the Health of the Public. Washington DC: The National Academies Press, p. 146-7.