Algorithm for the proper preparation of a periodic safety report

The algorithm for the proper preparation of the PSA can be presented in the form of 17 recommendations as follows.

1. It is necessary to track in advance the timing of the preparation of the PSAR and plan the work schedule in such a way that the compilers have enough time to collect the material, process it and prepare it, regardless of whether the preparation of the periodic safety report is carried out by the company’s own department of the a full range of pharmacovigilance services to order. The authors recommend starting preparation a few days before the closing of the reporting period (the timing depends on the qualifications of the compiler, his workload and the volume and complexity of the material being processed).
2. The qualifications of the PSUR compiler should ensure that they understand the current regulatory requirements, know all the information necessary to include in the PSR and how to work with this information.
3. To prepare and familiarize yourself with the main sections of the FOB, a standard form can be used that is publicly available on the Yandex disk (login: M20171123, password: 20171123).
4. When familiarizing with the standard form, the compiler must check its compliance with the current regulatory requirements — the legislation of the Russian Federation and the EAEU.
5. At the stage of preparation of the PSAR, PSR (periodic safety report) to order, if necessary, the standard form must be changed or supplemented by the PSAR compiler to bring it in line with the regulatory requirements that were relevant at the time of its preparation. The recommended procedure for this work for Word: on Windows — by substituting links in Review mode, for MacOS — by inserting comments in Insert mode.
6. Different regulatory legal acts can be used for different EAEU member states. At the time of this article preparation, for the Russian Federation these are the EAEU NPF Rules [2] and the Order of Roszdravnadzor No. 1071.
7. It is necessary to check that the design, section titles, their order of presentation and content correspond to the relevant regulatory requirements (which may differ in different countries), filling in the variable part in this template with your data, marked in italics.
8. General formal requirements for the design of the POB when submitting a document in Word format (* .rtf, * .doc, * .docx):

— paper sheet size: A4;

— margins (for vertical orientation of the sheet): left — 3 cm, right — 1.5 cm, top and bottom — 2 cm;

— font: Times New Roman;

— font size: 12 pt;

— numbering: each page is numbered starting from the first;

— headers and footers: a header or footer is required, with a brief reflection of the content;

— abbreviations: decipher at their first mention;

— references: given in accordance with the current edition of the Uniform Requirements

for manuscripts submitted to biomedical journals of the International Committee of Medical Journal Editors [6].

9. To achieve the goal of preparing the PSAR (periodic safety report), it is necessary to establish the compliance of the medicinal product safety information during the reporting period with the previously available information and, if necessary, make a decision based on the new data to amend the registration documentation.
10. It is necessary to fill in all sections of the standard POP form, using the official terminology of pharmacovigilance in Russian and universal methods of conducting an integrated analysis with the establishment of the degree of risk for all indications registered for this drug, in order to determine the final ratio of «benefit — risk», ensuring transparency of acceptance solutions, allowing to take into account quantitative and qualitative data and having the ability to integrate mathematical methods of calculation and implementation of models, as well as the availability of detailed guidelines for use, for example, the PrOACT-URL method, which is a structural assessment method that includes the provisions of decision theory (principles, processes, tools ) including 8 sequential steps: assessment of the problem, assessment of goals, alternatives, consequences, benefits, uncertainties, ratios of risks among themselves and related decisions [1].
11. When indicating the total number of patients exposed to the drug according to its use on the market, the established daily dose of the drug (DDD, Defined Daily Dose) is used, which is the calculated average maintenance daily dose of the drug used for the main indication in adults weighing 70 kg. The established daily dose of a drug is a technical unit of measurement that is not the same as the recommended daily dose, which depends on the severity, the nature of the course of the disease, the patient’s body weight, etc. It is defined only for the most widely used combination drugs that have been assigned an Anatomical Therapeutic Classification (ATC) code. This part of the report should be thoroughly checked if the preparation of the periodic safety report is outsourced by a full-service pharmacovigilance firm.
12. The generalized tabular data for PHB should be prepared in accordance with the terminological classifier of the Medical Dictionary for Regulatory Activities (MedDRA) of the current version.
13. The classification as Serious Adverse Reactions and Unexpected Adverse Reactions should be consistent with the methodology used to assess individual reported adverse reactions using the severity and foreseeability criteria established by law.
14. A search in the scientific and medical literature for publications containing important information on the safety of drug use should include information in the Medline®, eLibrary and EMBASE® databases for the reporting period.
15. The detection of medicinal product safety signals during the preparation of a periodic safety report should be carried out by analyzing the electronic database of individual messages on adverse reactions maintained by the DRU, formed on the basis of individual messages received from the spontaneous reporting system and published medical literature and other sources of information.
16. When assessing the effectiveness of risk mitigation measures, it is necessary to take into account the possible stay under additional monitoring, requests from the PS and the Risk Management Plan by the Ministry of Health of the Russian Federation for the previous and reporting period, monitoring the safety of the medicinal product as part of routine pharmacovigilance — the availability of information about the drug for doctors and patients ; the adequacy of information on possible risks when using the drug, as well as measures to minimize them in the Instructions for medical use and leaflet; limiting the excessive use of the drug by the size of the package.
17. The conclusion of the PSAR on the “benefit — risk” ratio is made on the basis of the results of a comprehensive analysis of information about the benefits and risks, as well as new and accumulated (cumulative) data on the safety of medicinal product use, carried out by the DRU. The conclusion should contain information about the presence or absence of grounds for additional measures to minimize risks when using the drug or making changes to the information on its safety profile.