Takeda's Statement on Recurrence Prevention and Disciplinary Action for the Issues Related to the Candesartan Antihypertensive Survival Evaluation in Japan (CASE-J)

October 03, 2014

Osaka, Japan, October 3, 2014 – Takeda Pharmaceutical Company Limited (“Takeda”) has previously  openly addressed through announcements and press conferences that, regarding the CASE-J study, an investigator-initiated sponsored research (IISR) related to the Takeda's hypertension medicine Blopress® (generic name: candesartan cilexetil), certain inappropriate promotional activities utilizing the results of this research were found to have occurred. The Company has also been open about the results of the third-party investigation by the law firm Jones Day that identified that there were multiple incidents of involvement and encouragement on the part of employees of Takeda during the CASE-J study that were inappropriate in the sense that they could arouse suspicion regarding the independency and neutrality of the IISR. However, there were no indications that data falsification or manipulation of the study occurred, nor were there any indications that there was any involvement thereto by Takeda employees.

Takeda has deliberated on measures to prevent recurrences of events such as this, a number of which have already been implemented, and it will continue to act comprehensively on these issues. Takeda's Compliance Committee, which included external legal counsel, has decided upon internal disciplinary action against the appropriate individuals based on their position and their responsibilities at both the time of occurrence and throughout the continuation of each event in question as well as the extent of the individual's involvement therein.

The measures for preventing recurrence (including those that have already been implemented) and internal disciplinary action that have been determined are specified as below.

I. Measures to prevent recurrences
1.Strengthening of the compliance promotion system
1)     Establishment of stricter review and management systems related to promotional materials
Effective April 2014, a unit responsible for compliance promotion was established within the Pharmaceutical Marketing Division. This unit is committed to enforcing thorough compliance and will conduct reviews on promotional materials as well. Furthermore, the review system has been strengthened by the addition of new members to the internal review function who are able to represent the legal perspective and the medical perspective. Additionally, the scope of materials for review has been expanded to include the secondary usage of materials (reusing of materials that were reviewed and approved in the past), and a process has been established to ensure the proper disposal of old materials.

2)     Promotion of the Japan Pharmaceutical Manufacturers Association's (JPMA) Code of Practice (COP)

In June 2013, Takeda established the internal “Guideline to promote JPMA’s COP” and, under the leadership of the Legal Department, has been promoting understanding of the contents of the COP and strict compliance through continuing education.

For the items above, Takeda will continue to comprehensively pursue even more effective operational procedures and review systems, as well as conduct continuing education.

2.  Strengthening of measures to report adverse events

A structure was implemented which streamlines both the gathering and reporting of safety information in IISR and contract research as well as the collecting and compiling of information regarding all adverse events that occurred during clinical studies. The safety information of Takeda’s products and all related events are to be immediately reported to the Safety Management Department within the Company. For that purpose, the guideline has been streamlined, and employees have been thoroughly informed of and educated on this.

3.  Guaranteeing transparency when supporting research such as IISR
1)      Noninvolvement of the Marketing Division in IISR
In addition to the education currently being conducted regarding the noninvolvement of its Medical Representatives in IISR, Takeda has been conducting comprehensive continuing education to the Marketing Division to ensure noninvolvement in IISR based on the “Pharmaceutical Marketing Division Conduct Guidelines” issued in June 2014.
2)    Development and adherence to a procedure manual for IISR

In order to verify the scientific significance of IISR and conduct strict reviews of matters related to conflict of interests (COI), the Medical Affairs Division, established within the Japan Development Center, will transition to a method that utilizes legal contracts when supporting IISR. These contracts clearly identify and specify the roles of the investigators and Takeda respectively as well as the noninvolvement of the Marketing Division. These contracts also clearly state how to appropriately manage COI issues in order to enhance transparency.

For the items above, Takeda will continue to implement its support based on the legal contracts, and will promote appropriate support to research activities by third party researchers, based on its guidelines regarding IISR.

4.  Stricter handling of donations

Effective May of this year, Takeda has strengthened the organizational structure and operational regulations for its Committee which assesses and reviews the appropriateness of donations, through which it will continue to rigorously eliminate conflict of interests and legal risks.

II. Disciplinary Action
1.Relevant directors

For related directors, depending on their individual scope of responsibility, a reduction of monthly remuneration within the range of 5% to 20% will be imposed for three months.

2.Relevant employees

Relevant employees will be formally reprimanded.

Through these measures, each and every one of Takeda’s employees will become more strongly conscious of Takeda’s mission to “strive towards better health for people worldwide through leading innovation in medicine,” and, at the same time, the thorough permeation of our Core Values of Takeda-ism (Integrity: Fairness, Honesty and Perseverance) will be further promoted throughout the company. Our united efforts are aimed not only regaining the trust that we have lost, but also earning an even higher level of trust from our stakeholders as well as society, and maintaining that trust steadfastly.

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