Recently, a long-term health concern has been identified in young Japanese women. These women have a high percentage of body fat despite a normal shape index indicator such as BMI. This condition is called marked obesity, and shows relative low lean body mass. Using an analogous determination, we investigated low percentage of muscle quantity (LM) in the extremities of young Japanese women (n=156) . The cross-sectional areas of muscle, subcutaneous fat, and bone were measured in the upper arm and thigh using ultrasonography. Extremity shape index (CSA_t/L) was defined as the total extremity cross-sectional area (CSA_t) divided by the length of the limb (L), Percent muscle in each extremity (% MA) was calculated from the ratio of muscle CSA to whole limb CSA. LM was defined as the percentage of muscle in the upper arm or thigh less than 1 SD below average and the limb shape index less than 1 SD above average. Nine of 91 subjects displayed LM for the upper arm. A similar proportion of subjects showed LM for the thigh (15/156) . The muscle mass and strength in the upper arm or thigh were compared between the subjects with LM and non-LM subjects with a similar shape index of extremity. There was a tendency towards lower muscle mass and muscle strength in the subjects with LM. From the same comparison, the subjects with LM showed a greater load on extremity muscles to sustain the body weight (i.e., body weight per unit of upper arm or thigh muscle CSA) . To mitigate the deleterious health consequences of low percent muscle quantity it is recommended that young Japanese women who display such a condition should participate in a resistance-training program.

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:
1. In order to clarify the research question, rationale and evidence for safety specification should be evaluated carefully.
2. It is essential to be considered in advance how to collect and analyze the safety data for detecting safety specification during clinical development.
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.
4. Continuous PDCA cycling is critical for RMP. The first survey or research will bring you next research question (s).
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.