ABSTRACT
MHLW released a guideline for Risk Management Plan (RMP) in April 2012, in order to manage the risk of pharmaceutical products from the development stage towards post marketing period. The guideline suggests to determine Safety Specification and to develop Pharmacovigilance Plan (PVP) and Risk Minimization Plan aligned to the ICH E2E guideline. However, in some of the RMPs, which had been published online (as of August 2014), conventional (Special) Drug Use Results Surveys are planned as a “universal” PVP regardless of the impact, severity and characteristics of the risks. Our JPMA taskforce (Data Science Expert Committee) summarized report and published in August 2014. In this report, we explained how to evaluate safety events based on evidence level for safety specification and how to develop PVP. Also, we would like to propose KAIZEN activities for RMP improvement as follows: <br>1. In order to clarify the research question, rationale and evidence for safety specification should be evaluated carefully. <br>2. It is essential to be considered in advance how to collect and analyze the safety data for detecting safety specification during clinical development. <br>3. Safety profiles should be discussed thoroughly on DSUR development among stakeholders in order to clarify safety specification at NDA. Research questions for each different risk and missing information should be established according to PECO, which will flow into appropriate PVP planning. <br>4. Continuous PDCA cycling is critical for RMP. The first survey or research will bring you next research question (s). <br>We expect all stakeholders, including clinical development specialists in industry, regulatory authorities, and academia, to have better understating of RMP principle and to manage and implement it more appropriately in a scientific manner.
ABSTRACT
Following the notice of “Guidance of Drug Risk Management Plan (RMP)” by MHLW in 2012, Japanese Society for Pharmacoepidemiology (JSPE) started. “A Task Force to make an acceptable Pharmacovigilance Plan (PVP) in Japan” from May 2013. As an outcome, the force published a check list used to evaluate individual PVP for a specific medicinal product together with the guidance for the use of the check list in “Yakuzai-ekigaku”, Journal of JSPE. During over one year since RMP was implemented, RMPs with PVP (included as a component of RMP) were published for 40 compounds and we tried to evaluate those PVPs using the check list we developed. It turns out that an answer to the first question in the check list “Is the necessity of additional PVP described?” was “No” for all 40 PVPs. More serious problem was that one of a few stereotyped study designs was selected in all of the 40 PVPs. No rationale was given to explain why the selected study design could achieve the study aim associated with the important problems specified in the section of safety specification. We conclude that although RMP has been implemented over one year ago, the conventional study design remains to be used in the actual PVP and the main messages of ICH E2E guideline have not been fully realized.
ABSTRACT
A Task Force team consisting of members from pharmaceutical companies --a central player to develop and implement RMP (Risk Management Plan)-- as well as health care professionals and members from academia was established in JSPE. The Task Force developed guidance for scientific approach to practical and ICH-E2E-compliant Pharmacovigilance Plan (PVP) stated in Japanese Risk Management Plan issued in April 2012 by the Ministry of Health, Labour and Welfare. The guidance contains the following topics.<br>1．Introduction: JSPE's activities and this task force's objectives for pharmacovigilance activities<br>2．How to select Safety Specification (SS) and describe its characteristics<br>・Selection of SS<br>・Characterization of SS<br>・Association with Research Questions (RQ)<br>3．How to define and describe RQ<br>・What is RQ ?<br>・RQ interpretation in other relevant guidelines<br>・Methodology to develop RQ for PVP with examples<br>・Best approach to integrating PVP for whole aspects of safety concern<br>4．How to optimize PVP for specific RQ<br>・Routine PVP or additional PVP ?<br>・Additional PVP design (RQ and study design, RQ structured with PICO or GPP's research objectives, specific aims, and rationale)<br>・Checklist to help develop PVP<br>5．Epilogue:<br>・What can/should be “Drug use investigation” in the context of ICH-E2E-compliant PVP.<br>・Significance of background incidence rate and needs for comparator group<br>・Infrastructure for the future PVP activities<br>6．Appendix: Checklist to help develop PVP activities in RMP<br>The task force team is hoping that this guidance help develop and conduct SS and PVP in accordance with ICH E2E, as stated in Japanese Risk Management Plan Guideline.