Topics Workshop for Persons Responsible for Product Information Overview Management and Practice Management in FY2021" was held.
On March 29, 2022, the "FY2021 Training Course for Persons Responsible for Product Information Overview Management and Practical Responsible Persons" was held in an online format. Approximately 600 people participated on the day, 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 companies.
The following is a report on the outline of this training session.
The venue
1. opening remarks
Mitsuhiro Kondo, Chairperson, JPMA Review Board of Ethical Drug Product Information Brochure
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 workshop, the following issues were introduced and explained: (1) subgroup analysis, (2) false, exaggerated, or misleading expressions, (3) emphasis on safety, and (4) assurance, etc., which were frequently pointed out as Class II issues in the past three review meetings. Explanation will be given on (1) subgroup analysis, (2) false, exaggerated, or misleading statements, and (3) emphasis on safety and assurance, etc., so please refer to the presentation as a reference for your daily review.
He also introduced Mr. Yasushi Komiyama, Vice Chairperson of the JPMA Review Board of Ethical Drug Product Information Brochure, who will deliver a special lecture. He is also Chairperson of the Data Science Subcommittee of the Drug Evaluation Committee, and is a leading expert in the field of statistics for drug development.
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 Review Board of Ethical Drug Product Information Brochure
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, JPMA Review Board of Ethical Drug Product Information Brochure
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
JPMA Review Board of Ethical Drug Product Information Brochure Toshihiko Saeki, Member
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
Yuki Kuroda, Member, Review Board of Ethical Drug Product Information Brochure, JPMA
Examples of emphasizing and assuring safety" "Points to keep in mind when introducing specific adverse reactions"
3. special lecture
Explanation of the Guidelines for Preparation from a Statistical Perspective
Yasushi Komiyama, JPMA Review Board of Ethical Drug Product Information Brochure, Vice Chairperson
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 an important piece of information for physicians when selecting 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
JPMA Managing Director Norio Tanaka
In closing, he thanked the nearly 600 participants who attended this workshop for their daily Review Board of Ethical Drug Product Information Brochure and their high level of interest in it, and also for the fact that there were no major problems that would lead to changes or revisions of the preparation guidelines, although some minor points were raised in the monitoring project under the Guidelines for Marketing Information Provision Activities. 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" rather than "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 JPMA Code of Practice defines "promotion" not as so-called "sales promotion," but as "the provision, collection, and communication of pharmaceutical information to medical professionals and the promotion of the appropriate use and dissemination of ethical drugs based on such information. 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 the company's 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 rules that JPMA member companies should naturally follow, 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 JPMA Code of Practice "1.1 Scope", which states that "Member companies shall always base their decisions on whether their T-row behavior is in accordance with the intent of the JPMA Code, regardless of whether or not it is specifically mentioned in the JPMA Code". He concluded the meeting by asking for the continued understanding and cooperation of all member companies.
( Masahiko Kimura, Review Board of Ethical Drug Product Information Brochure)