Topics Briefing session on the revision of the "Guidelines for the Preparation of Product Information Summaries for Ethical Drugs" was held
On October 13, 2023, a web briefing on the revision of the "Guidelines for the Preparation of Product Information Summaries, etc. for Ethical Drugs (hereinafter referred to as "Guidelines")" was held. Approximately 1,800 participants, including pharmaceutical association member companies, non-member companies, and advertising agencies, showed a high level of interest in the revision of the Guidelines, which are voluntary standards of the Pharmaceutical Manufacturers Association of Japan regarding the preparation of promotional materials, and enthusiasm for the creation of appropriate materials. The following is a summary of the meeting.
The venue
Table 1 Program of the Briefing Session on the Revision of the Guidelines for the Preparation of Product Information Summaries for Ethical Drugs
1. opening remarks
At the opening of the meeting, Mr. Mitsuhiro Kondo, Chairperson of the Prescription Drug Product Information Outline Review Committee of the Pharmaceutical Manufacturers Association of Japan (PMAJ), thanked the approximately 1,800 people from member companies, non-member companies, and advertising agencies who had registered for this briefing session.
He also introduced the purpose of the revision of the guidelines, the period during which the revised guidelines will be disseminated, their operation, and the content of today's briefing.
In order to ensure the proper use of pharmaceutical products, the appropriateness of the information provided is of utmost importance. If the standards for appropriateness differ from company to company, or if the information is presented inaccurately, the medical professionals receiving the information will not be able to make accurate judgments or evaluations, which will ultimately be to the detriment of patients. To prevent this from happening, it is important to have materials that provide appropriate information. The guidelines are designed to enable each company to create appropriate materials based on certain standards.
The basis for providing accurate information is the materials prepared by each company, and we have urged them to continue to prepare appropriate materials in accordance with the Guidelines for the Preparation of Materials.
Revision of the Guidelines for the Preparation of Product Information Summaries for Prescription Drugs (Preparation Guidelines)
The Pharmaceutical Manufacturers Association of Japan (PMAJ) Prescription Drug Product Information Review Committee gave an explanation of the revision of the preparation guidelines.
Explanation (1) General Revision
Member Masahiko Kimura explained the revision in general.
The revision was made to revise "contents that may cause misunderstanding" for medical professionals and to make the contents "more accurately conveyed" to them.
The main changes are as follows: "Clarification of the concept when preparing product information summaries," "Changes to more accurately inform healthcare professionals about clinical trials," "Partial changes when citing diagnostic and treatment guidelines prepared by academic societies as sources to promote proper use," "Partial exclusion of daily activity and quality of life from reference information," and "Changes to the content of the review committee report to make it better known to healthcare professionals. The revisions include the following: "Partial exclusion of the reference information on daily activity and QOL"; and "Changes and improvements to the information that has been made known in the review committee reports.
The Pharmaceutical Manufacturers' Association of Japan (PMAJ) Prescription Drug Product Information Outline Review Committee
Mr. Masahiko Kimura, Member
He asked the participants to understand that they should prepare materials in compliance with the revised guidelines, although there will be a period of time for dissemination of the information as described below.
| The event concluded with a speech by Mr. Takafumi Adachi, Director of Public Relations. | The revision shall be effective October 1, 2023 (with a 9-month period of dissemination) |
| The event concluded with a speech by Mr. Takafumi Adachi, Director of Public Relations. | Effective July 1, 2024 New materials: on or after July 1, 2024; existing materials: at the time of material revision on or after July 2024 |
Explanation (2) Basic notes and data
Committee Member Hideaki Kami explained the main points of the revision as follows.
| The event concluded with a speech by Mr. Takafumi Adachi, Director of Public Relations. | Addition that if the CQs and statements in the guideline include statements outside the scope of approval for the company's own drug, those CQs and statements cannot be cited, as the CQs and statements are to be written in their original language. |
| The event concluded with a speech by Mr. Takafumi Adachi, Director of Public Relations. | Addition that if the guideline includes a statement that is outside the approved scope of the company's drug product, it should not be included in the guideline. |
| The event concluded with a speech by Mr. Takafumi Adachi, Director of Public Relations. | Even if a guideline includes a statement that is not approved for the company's drug, if the electronic package insert includes a statement such as "see the most recent guideline" in the Indications and Dosage & Administration section and it is clear that the statement in the specific guideline was evaluated at the time of approval of the drug, then the guideline may not be cited. Addition of the fact that the drug can be used only for those parts of the drug that were evaluated at the time of approval. |
The Japan Pharmaceutical Manufacturers Association (JPMA) Prescription Drug Product Information Outline Review Committee
Mr. Hideaki Ue, Member
| The event concluded with a speech by Mr. Takafumi Adachi, Director of Public Relations. | Addition of commentary on "text indicating efficacy results," which is to be written in the same or larger font size as the text indicating efficacy results, when describing safety. |
| The event concluded with a speech by Mr. Takafumi Adachi, Director of Public Relations. | Addition of the fact that clear and generalized definitions of evaluation indices and evaluation scores do not fall under the category of reference information. |
| The event concluded with a speech by Mr. Takafumi Adachi, Director of Public Relations. | Addition of the requirement that when the results of subgroup analysis are presented, they should be described together with the results of the analysis of the overall population, if the analysis of the overall population is conducted. |
Explanation (3) General/Specific Item Product Information Overview
Commissioner Hiroe Takeuchi explained the main points of the revision as follows.
| The event concluded with a speech by Mr. Takafumi Adachi, Director of Public Relations. | (2) The development history of the drug is not the status of its approval overseas, but rather the fact that an application for approval is pending overseas or that a study for an unapproved disease in Japan that is being conducted overseas cannot be described. |
| The event concluded with a speech by Mr. Takafumi Adachi, Director of Public Relations. | Response when clinical results that include unapproved indications or effects or dosage and administration are described in the characteristics (sex) |
| The event concluded with a speech by Mr. Takafumi Adachi, Director of Public Relations. | Addition of notes on how to describe the results of each clinical trial and that they are not regarded as characteristics when only the results of each clinical trial are described together. |
| The event concluded with a speech by Mr. Takafumi Adachi, Director of Public Relations. | Addition of the requirement to describe the results of validation analysis or nominal P-values in a way that they can be clearly understood, and explanation of the results of validation analysis and nominal P-values. |
| The event concluded with a speech by Mr. Takafumi Adachi, Director of Public Relations. | Addition of a response to cases where there are no serious adverse reactions in the description of characteristics |
The Pharmaceutical Association of Japan (PAK) Prescription Drug Product Information Outline Review Committee
Hiroe Takeuchi, Member
| The event concluded with a speech by Mr. Takafumi Adachi, Director of Public Relations. | Addition of commentary on the results of studies in which the drug was fairly compared to the control drug. |
| The event concluded with a speech by Mr. Takafumi Adachi, Director of Public Relations. | Modification of the description in the opening note in the original appraisal document. |
| The event concluded with a speech by Mr. Takafumi Adachi, Director of Public Relations. | Addition of clear description of validation analysis items in the study design |
| The event concluded with a speech by Mr. Takafumi Adachi, Director of Public Relations. | Addition of a response to the termination of the validation procedure in the Gate Keeping Strategy and the closed validation procedure, etc. |
| The event concluded with a speech by Mr. Takafumi Adachi, Director of Public Relations. | Addition of actions to be taken when specific adverse reactions/adverse events are to be confirmed in advance. |
| The event concluded with a speech by Mr. Takafumi Adachi, Director of Public Relations. | Modification of relevant information in the version of specific items. |
| The event concluded with a speech by Mr. Takafumi Adachi, Director of Public Relations. | Modification of measures to be taken when there is no safety statement in the original article. |
Explanation (4) Advertisements and other materials to be published in specialized magazines (paper)
Committee Member Naoaki Okimura explained the main points of the revision as follows
| The event concluded with a speech by Mr. Takafumi Adachi, Director of Public Relations. | Addition of description of GS1 barcode |
| The event concluded with a speech by Mr. Takafumi Adachi, Director of Public Relations. | Addition of "urgently approved drugs" and "conditionally approved drugs" to regulatory categories |
| The event concluded with a speech by Mr. Takafumi Adachi, Director of Public Relations. | Change to the requirement that side effects to be listed in the DI for normal advertisements should be listed for serious side effects and only major side effects should be listed for other side effects if not all of them can be listed |
| The event concluded with a speech by Mr. Takafumi Adachi, Director of Public Relations. | Move part of the explanation of "Advertisements mainly by product name only" to the main text. |
| The event concluded with a speech by Mr. Takafumi Adachi, Director of Public Relations. | When clinical trials are described in advertisements in the form of articles or in the recordings of lectures and research meetings hosted or co-hosted by the company, "Please refer to page XX for information on precautions, including warnings and contraindications," etc., at the top of the first page introducing the clinical results in a larger font size than the main text" is added. |
The Japan Pharmaceutical Manufacturers Association (JPMA) Prescription Drug Product Information Outline Review Committee
Naoaki Okimura Member
| The event concluded with a speech by Mr. Takafumi Adachi, Director of Public Relations. | Addition of "In headlines and titles, do not use expressions that are false or exaggerate efficacy or emphasize or guarantee safety" in advertisements in the form of articles and in the collection of records of lectures and research meetings hosted or co-hosted by the company |
| The event concluded with a speech by Mr. Takafumi Adachi, Director of Public Relations. | Addition of "When describing study results, describe them in accordance with the study design" in the presentation contents. |
| The event concluded with a speech by Mr. Takafumi Adachi, Director of Public Relations. | Addition of the following to slide sets provided for the purpose of lectures to medical professionals at company-sponsored or co-sponsored lecture meetings: "If there are any conflicts of interest with the company, they should be described along with bibliographic information. |
| The event concluded with a speech by Mr. Takafumi Adachi, Director of Public Relations. | Addition of the following to the presenter's comments in the record of lectures and seminars hosted or co-hosted by the company: "Avoid definitive expressions such as impressions based on treatment experience or impressions not based on data, and do not emphasize or guarantee efficacy or safety. |
| The event concluded with a speech by Mr. Takafumi Adachi, Director of Public Relations. | Addition of "Literature on the efficacy of the company's drugs should not include review articles, reviews, articles, contributions, etc." in the literature annex. |
3. on the scientific aspects of the preparation procedure
Mr. Yasushi Komiyama, Vice-Chairman of the Pharmaceutical Manufacturers Association of Japan (PMAJ), provided the following explanations to ensure a correct understanding of the preparation procedure.
| The event concluded with a speech by Mr. Takafumi Adachi, Director of Public Relations. | Explanation of the meaning of the P-value and the principles set forth by the American Statistical Association (ASA) statement on the misuse of the P-value. |
| The event concluded with a speech by Mr. Takafumi Adachi, Director of Public Relations. | The logic of the test is backward reasoning, not logic that can show that there is no difference. |
| The event concluded with a speech by Mr. Takafumi Adachi, Director of Public Relations. | Small P-values, such as P=0.01, are not strong evidence. |
| The event concluded with a speech by Mr. Takafumi Adachi, Director of Public Relations. | P-values from validative analysis and nominal P-values |
| The event concluded with a speech by Mr. Takafumi Adachi, Director of Public Relations. | Validation framework |
| The event concluded with a speech by Mr. Takafumi Adachi, Director of Public Relations. | 2. how to enhance evidence based on internal and external consistency |
The Pharmaceutical Manufacturers Association of Japan (PMAJ) Prescription Drug Product Information Outline Review Committee
Yasushi Komiyama Vice-Chairman
| The event concluded with a speech by Mr. Takafumi Adachi, Director of Public Relations. | Note on P-values in Multiple Comparison Methods |
| The event concluded with a speech by Mr. Takafumi Adachi, Director of Public Relations. | Regarding the two purposes of subgroup analysis, (1) exploratory study of factors affecting efficacy and safety, and (2) study of efficacy/safety in a population of particular interest |
4. on sales information activities and informational materials
Mr. Michiaki Furue, Advertising Guidance Officer of the Monitoring Guidance and Narcotics Control Division of the Ministry of Health, Labour and Welfare, said that the large number of participants in this briefing session showed a high level of interest in the revised guidelines and a high awareness of the need to comply with the revised guidelines. He also mentioned that the Division had been contacted in advance and consulted on the details of the revision.
The Monitoring and Guidance and Narcotics Control Division's "Monitoring of Activities to Provide Sales Information on Ethical Drugs" is not only based on the "Pharmaceuticals and Medical Devices Act," the "Standards for Proper Advertising of Drugs, etc.," and the "Guidelines for the Provision of Sales Information," but also on the "Guidelines for the Provision of Sales Information. He also introduced that this project is being promoted by examining inappropriate cases with reference not only to the "Guidelines for Provision of Marketing Information" but also to the "Guidelines for Preparation of Guidelines.
He also briefly introduced the monitoring project for FY2022. his impression through the FY2022 project is that many companies have improved their internal systems, and the number of cases of violation in the promotional materials themselves has decreased. However, even when product information summaries and other materials are properly prepared in accordance with the preparation guidelines, inappropriate promotions are still reported in the course of actual use.
Michiaki Furue, Advertising Guidance Officer, Monitoring and Guidance and Narcotics Control Division, Pharmaceutical Affairs Bureau, Ministry of Health, Labour and Welfare
He concluded with the following words: "I hope that everyone will first have a clear understanding of what has been introduced today and prepare product information summaries, etc., in accordance with the revised preparation guidelines, so that the examination departments can conduct appropriate examinations and use the information appropriately in their information provision activities.
5. closing remarks
In closing, Mr. Yoshiyuki Ishida, Executive Director of the Pharmaceutical Manufacturers Association of Japan (PMAJ), expressed his gratitude to the many people who participated in the meeting and to those who worked so hard on this revision.
My own understanding from reading the works of behavioral economists and cognitive psychologists is that humans are easily mislead. Medical professionals and pharmaceutical companies may be equally prone to misleading. The concept of this revision is to eliminate misleading and communicate more accurately. Even if materials are properly prepared, there is a possibility that they may be misleading. The point that needs to be emphasized is not only to create appropriate materials, but also to establish a method to properly explain the information. I mentioned that I would like to contribute to good medical care by providing appropriate information and promotional activities not only to medical representatives (MRs) and medical science liaisons (MSLs) but also to medical professionals.
Mr. Yoshiyuki Ishida, Executive Director, Pharmaceutical Manufacturers Association of Japan
In closing, he said, "I would like you to first understand the revised preparation guideline and prepare appropriate materials, and beyond that, I would like you to think about how to properly utilize those materials and how to ensure that they are accurately understood. I believe that by doing so, the quality of information provision in the pharmaceutical industry will be enhanced," he concluded.
( Masahiko Kimura, Member of the Association for Prescription Pharmaceutical Product Information Summary Review Committee)