Topics Held the "FY2021 Workshop for Persons Responsible for Product Information Outline Management and Persons Responsible for Practice".
On March 29, 2022, the "FY2021 Workshop for Persons Responsible for Product Information Outline Management and Practice Managers" was held in an online format. Approximately 600 people participated in the event, mainly those in charge of product information overview management and practical affairs at member companies, as well as those in charge of material review at their own companies.
The following is a report on the outline of this training session.
The venue
1. opening remarks
Mitsuhiro Kondo, Chair, Product Information Outline Review Committee, Pharmaceutical Manufacturers Association of Japan (PMAJ)
At the outset, he expressed his gratitude to the member companies for their cooperation in complying with the Guidelines for the Preparation of Product Information Summaries for Prescription Drugs (hereinafter referred to as "the Guidelines") and to the more than 600 people who attended today's workshop.
In this training session, he introduced and explained the following issues that have been frequently pointed out as Class II issues in the past three review meetings: (1) subgroup analysis, (2) false, exaggerated, or misleading expressions, (3) emphasis on safety, and (4) assurance of safety. He also introduced and explained the following points, which are often pointed out in Class II at the past three review meetings: (1) subgroup analysis, (2) false, exaggerated, or misleading expressions, and (3) emphasis on safety.
He also introduced Mr. Yasushi Komiyama, Vice-Chairman of the Product Information Outline Review Committee of the Pharmaceutical Manufacturers Association of Japan (PMAJ), who will deliver a special lecture. Mr. Komiyama is a leading expert in the field of statistics for drug development and is also the chairman of the Data Science Committee of the Drug Evaluation Committee.
In the field of drug development, the GCP Renovation is currently under discussion, and the style of drug development is changing drastically, including the revitalization of discussions on the use of real world data (RWD) such as registries, and discussions in the Diet on the urgent approval system. He concluded by saying that it is the responsibility of companies that market pharmaceuticals to provide medical professionals with correct and appropriate information, data, and results of pharmaceuticals, and that this training session was planned to ensure that the information provided to medical professionals is correctly disseminated.
Sharing of cases pointed out at the Product Information Summary Review Meeting
This training session was planned to promote understanding of the preparation guidelines, and included case studies of items that were frequently pointed out as "Class II" at the past (113th, 114th, and 115th) review meetings. Below is the training program of the day.
Explanation (1)
Subgroup Analysis
Katsuto Murase, Member, Product Information Outline Review Committee, The Pharmaceutical Society of Japan
The following is the training program of the day.
Specify the items to be introduced in the analysis plan, etc.
Explanation (2)
False, exaggerated, or misleading statements" "False, exaggerated, or misleading statements
Toshihiko Saeki, Member of Product Information Outline Review Committee, Pharmaceutical Society of Japan
The following topics were covered during the training: "Use of the word 'maximum,'" "Use of the word 'assurance,'" "Considerations for comments by medical professionals," and "Points to keep in mind when using the word 'excellent.
Explanation (3)
Emphasis and assurance of safety" and "Specific side effects
Yoshiki Kuroda, Member of Product Information Outline Review Committee, Pharmaceutical Association of Japan
Examples of emphasizing and assuring safety" "Points to keep in mind when introducing specific adverse reactions"
3. special lecture
Explanation of Preparation Guideline from Statistical Perspective
Yasushi Komiyama Vice-Chairman, Product Information Outline Review Committee, The Pharmaceutical Society of Japan
At the beginning of the lecture, he informed the audience that the purpose of this presentation was to "deepen understanding of the rules regarding statistics in the preparation guidelines" and that he wanted the audience to understand "the necessity of statistical rules and how not complying with such rules may cause misunderstanding among medical professionals.
He was then asked by the audience about the purpose of creating the materials, and he stated, "Communicating without misunderstanding what effects and what risks can be expected when the drug is used on the patient in front of you should lead to the proper use of the drug, and the sales volume is a consequence of that. He stated that the volume of sales is a consequence of this.
In his speech, he talked about the rules of statistics, saying that various data are taken in clinical trials/clinical studies, but these data are "cut data" under certain conditions, and statistical analysis has been used to interpret these data, but there is a misperception that "statistical analysis (especially P-values) endorses what we want to say. He explained that there is a widespread misconception that "statistical analysis (especially P-values) endorses what we want to say. He also explained that without correcting this erroneous perception, medical professionals receiving the information would not be able to properly judge "how reliable the information is." Therefore, he introduced that the rules of statistics were established as one of the guidelines to move this situation in the right direction.
The following five concepts stipulated in the rules for preparation guidelines were then explained. The following is an overview.
(1) Presentation of the results of statistical analysis
The "ASA Statement on Statistical Significance and P-values" published by the American Statistical Association (ASA) was introduced. It remains extremely important to "describe statistical analysis methods and their results" in validative analyses, including in the future, and these are currently applied to results other than validative analyses as well, but once it becomes known that the presentation of uninterpretable P-values is meaningless, it will be less important to specify the analysis methods for uninterpretable P-values. However, once it becomes known that the presentation of uninterpretable P-values is meaningless, it will be understood that it is not so important to specify the analysis method for uninterpretable P-values.
Regarding the two aspects of confidence intervals (accuracy of statistical estimation and correspondence to statistical testing), he stated that in stating confidence intervals in validity of less than 10 cases, the width of the confidence interval is wide for a small number of cases, which would indicate that it gives little information.
(2) Description of verification items (regarding positive and negative results)
He explained the weight of the word "validation" (the strongest method of proof = validation), and stated that only P-values obtained in validative analysis can be interpreted in relation to "what we want to say" and that other P-values cannot be interpreted in any way by themselves, which is why it is important to clearly state which results are from validative analysis. Therefore, it is important to clearly state which results are the results of the validation analysis.
(3) Preliminary rules
He explained again using the 2019 training slides.
(4) Covariates, etc.
In his explanation, he introduced that analysis to convey what background factors make patients respond differently (or more likely) should be important information for physicians when choosing a treatment plan.
In the past, the methods of complementation of missing values were often used, such as LOCF, or tabulation and analysis ignoring missing values, but recently, various complementation methods have been used, such as estimating changes over time using data for the entire group (MMRM), or changing the complementation method according to the reason for missing values (multiple imputation), etc. He also introduced the importance of clearly stating the completion method, since different results may be obtained depending on the completion method.
(5) Concept of subgroup analysis
He introduced the "Proposal for Reviewing the Way of Advertisement of Ethical Drugs," stating that not all results of subgroup analysis are unreliable, but the essence of the problem lies in making some claims based on analysis results that have not been pre-specified and may have been obtained only by chance, or giving the impression of such claims without explicitly stating them. He stated that the essence of the problem is to make some claim or to give an impression without explicitly making that claim.
At the end of the special lecture, he introduced that the current rules for statistics are not perfect, and that he is considering revising the guidelines to bring them closer to what they should be and to be able to accommodate new methods, etc. He also referred to the review committee reports and other documents. He concluded by stating the need to follow up on audit trends by referring to audit meeting reports and other information.
4. closing remarks
N. Tanaka, Executive Director of the Pharmaceutical Manufacturers Association of Japan (PMAJ)
In closing, he expressed his gratitude to the nearly 600 participants who attended the workshop due to the high level of interest in the daily review and preparation of product information summaries, and to the fact that there were no major problems that would lead to changes or revisions in the preparation guidelines, although there were some minor issues in the monitoring project under the Guidelines for Activities to Provide Marketing Information. He also expressed his gratitude to the participants for their participation.
He also requested the participants to continue their efforts to promote the "3 no's" (do not make inappropriate materials, do not pass inappropriate materials through internal screening, and do not use correct materials inappropriately), and commented that it would be better to refer to "materials and promotional materials" instead of "sales promotion materials" as a question regarding each company's own materials. We commented that it would be better to use the term "materials and promotional materials" rather than "promotional materials.
In the first place, the Pharmaceutical Manufacturers Association Code of Practice defines "promotion" not as so-called "sales promotion" but as "providing, collecting, and communicating pharmaceutical information to medical professionals and promoting the appropriate use and dissemination of ethical drugs based on such information," and furthermore, the pharmaceutical industry has been working on the "promotion of pharmaceuticals in the 21st century" since 1993, when the He explained that since the "Roundtable Conference on the State of Pharmaceuticals in the 21st Century" in 1993, the term "sales promotion (sales promotion)" is no longer used because it has the image of prescribing pharmaceuticals to patients who do not need to take them, thereby increasing sales.
He introduced the proposal made at the "MR Forum" held on August 26, 2021, to change the name of MRs to "proper use promoters" instead of "pharmaceutical information officers." Based on this idea, the name of "materials and promotional materials" was changed to "proper use promotion materials," the company's product information sessions to "proper use promotion briefings," and company lectures to "proper use promotion meetings. He also suggested that the industry itself change the names of its own product briefings to "materials for promoting proper use" and its own lectures to "lectures for promoting proper use" in order to promote proper use in the true sense.
Finally, he explained that although the guidelines are naturally rules to be followed by member companies of the Pharmaceutical Manufacturers Association of Japan (PMAJ), they are not perfect, and the reason for this is that they may need to be revised as science and technology advance. He also introduced the statement in the "1.1 Scope" of the Pharmaceutical Manufacturers Association of Japan Code of Practice that "Member companies shall always base their decisions on whether their actions are in accordance with the intent of the Pharmaceutical Manufacturers Association of Japan Code, regardless of whether or not they are specifically mentioned in the Code" and added that "regardless of whether or not they are specifically mentioned in the guidelines, they shall always base their decisions on whether or not their actions are in accordance with the intent of the guidelines. He concluded the meeting by asking for the continued understanding and cooperation of all member companies.
( Masahiko Kimura, Product Information Outline Review Committee)