Definitions

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1. Definitions
In force from:
11.01.2016

Post-authorisation safety study (Article 3a (1) of AoP)

Post-authorisation safety study of a medicinal product for human use shall mean any study relating to an authorised medicinal product for human use conducted with the aim of identifying, characterising or quantifying a safety hazard, confirming the safety profile of the medicinal product, or of measuring the effectiveness of risk management measures.

Non-interventional post-authorisation study (Article 3a (2) of AoP)

Non-interventional post-authorisation safety study of a medicinal product for human use shall mean any study in which an authorised medicinal product for human use is prescribed in the usual manner in accordance with the terms of the marketing authorisation and in which the assignment of the patient to a particular therapeutic strategy is not decided in advance by a study protocol but falls within current practice and the prescription of the medicine by the attending physician is clearly separated from the decision to include the patient in the study, while no additional diagnostic or monitoring procedures are applied to the patients and epidemiological methods are used for the analysis of collected data; non-interventional post-authorisation studies include epidemiological, pharmacoeconomic and research studies.

Non-interventional post-authorization safety study

It is a subset of post-authorisation safety studies covered by this guideline. The term “noninterventional post-authorisation safety study” is reserved only for a study that meets all the following conditions:

  1. The study is conducted with the aim of identifying, characterising or quantifying a safety hazard, confirming the safety profile of the medicinal product, or of measuring the effectiveness of risk management measures.
  2. The studies shall not be performed where the act of conducting the study promotes the use of a medicinal product.
  3. Payments to healthcare professionals for participating in non-interventional postauthorisation safety studies shall be restricted to the compensation for time and expenses incurred.
  4. Only authorised medicinal products in accordance with the terms of the marketing authorisation are used in the study.
  5. Medicinal products in the study are used in accordance with the current effective SmPC. Any changes to the SmPC or other regulatory actions regarding the safe use of the products must be immediately taken into consideration in the performed studies.
  6. Medicinal products used in the study have to be already marketed in the Czech Republic and available in the usual distribution network.
  7. Medicinal products in the study are prescribed and dispensed in the usual way, i.e. prescribed by a physician and dispensed by a pharmacist based on a prescription. No promotional samples can be used.
  8. Medicinal products in the study shall not be provided for free or at discount compared to their current availability in the market. This also applies to the additional payments in pharmacy.
  9. The selection of patients assigned in the study shall not be affected in advance and must depend solely on the decision of the attending physician as a part of the current practice. The participating physician should comply with the approved protocol of the study and the approved SmPC during the study.
  10. No additional diagnostic or monitoring procedures shall be applied to the patients and epidemiological methods are used for the analysis of collected data. All diagnostic and therapeutic procedures that are applied to the patients included in the study shall be reimbursed in the usual manner, i.e. without any support from the organizer of the study. Some exceptions are situations where diagnostic procedures recommended in the SmPC are not sufficiently performed in current practice and these procedures are necessary for drug safety monitoring.

Studies that do not meet all 10 conditions may not be described as “non-interventional postauthorisation safety studies”. In case that MAH submits the documentation to a study that cannot be described as non-interventional safety study, SÚKL will inform the MAH that it is necessary to change the type of study to a marketing study, PAES (post-authorisation efficacy study), other type of the study or a clinical trial.

In a study, which is described as a retrospective study, only such data may be used, that have been recorded on data media (including paper) before the first contact between the organizer of the study, or its representative, and the physician.

Study protocol (research plan)

All PASS must have a written study protocol before the study commences. The study should follow a scientifically sound study protocol developed by individuals with appropriate scientific background and experience. Strongly recommended and appropriate format and content of the protocol are provided in the document titled Guidance for the format and content of the protocol of non-interventional postauthorisation safety studies (https://www.ema.europa.eu/docs/en_GB/document_library/Other/2012/10/WC500133174.pdf).

Basic information that shall be included in each PASS protocol (according to Annex III of the Commission Implementing Regulation No. 520/2012):

    • Title page (informative title including a commonly used term indicating the study design and the medicinal product substance or drug class concerned, subtitle with a version identifier and dates of the last version)
    • Marketing authorisation holder
    • Responsible parties (author of the protocol, collaborating physicians and investigators, list of collaborating institutions and other relevant study sites)
    • Abstract – stand-alone summary of the study protocol
    • Amendments and updates to the study protocol
    • Milestones and timetable of the study stating the following milestones: start of data collection, end of data collection, final study report
    • Rationale and background
    • Research question and objectives
    • Research methods
    • Protection of human subjects
    • Management and reporting of adverse reactions/ events
    • Plan for disseminating and communicating study results
    • References

The format and content are obligatory for the imposed studies and strongly recommended for studies performed voluntarily by the marketing authorisation holder.

SÚKL will publish protocol abstracts of studies conducted in the Czech Republic. In case that the study is conducted also in other Member States, it is possible to submit the protocol in English; otherwise the protocol is presented in Czech. The abstract of the protocol must be always submitted also in Czech.

Recommended format of the abstract (according to Annex III of the Commission Implementing Regulation No. 520/2012):

  • Title with subtitles including version and date of the protocol, name and affiliation of main author
  • Rationale and background
  • Research question and objectives
  • Study design
  • Subjects and study size, setting
  • Variables
  • Data sources
  • Discussion
  • Milestones

Progress reports

A progress report may be requested by SÚKL at any time during the study conduct, particularly in situations requiring information regarding safety concern arising from the study.

Final study report

The marketing authorisation holder shall submit the final study report to SÚKL within 12 months of the end of data collection. If the study has not been conducted or was discontinued, the MAH shall submit a document replacing the final study report and provide the reasons for termination of the study. Strongly recommended and appropriate format and content of the final study report are provided in the document titled Guidance for the format and content of the final study report of non-interventional post-authorisation safety studies (https://www.ema.europa.eu/docs/en_GB/document_library/Regulatory_and_procedural_guideline/20 13/01/WC500137939.pdf).

Basic information that shall be included in each PASS final study report (according to Annex III of the Commission Implementing Regulation No. 520/2012):

    • Title page (informative title including a commonly used term indicating the study design and the medicinal product substance or drug class concerned,, subtitles with date of final report and name and affiliation of the main author)
    • Abstract – stand-alone summary of the final study report
    • Marketing authorisation holder and investigators (names, titles, degrees, addresses and affiliations of the principal investigator and all co-investigators and list of collaborating institutions and relevant study sites)
    • Milestones and timetable of the study (planned and actual dates)
    • Rationale and background Research question and objectives
    • Amendments and updates to the protocol
    • Research methods
    • Results
    • Discussion and conclusion
    • References

The format and content are obligatory for the imposed studies and strongly recommended for studies performed voluntarily by the marketing authorisation holder.

If the results of the study are used for a scientific publication, it is recommended to familiarize SÚKL with the final manuscript of the paper.

SÚKL will publish abstracts of the final study reports of the studies conducted in the Czech Republic. In case that the study is conducted also in other Member States, it is possible to submit the final study report in English; otherwise the final study report is presented in Czech. The abstract of the final study report must be always submitted also in Czech.

Recommended format of the abstract of the final study report (according to Annex III of the Commission Implementing Regulation No. 520/2012):

  • Title, with subtitles including date of the abstract and name and affiliation of main author
  • Keywords (not more than five keywords indicating the main study characteristics)
  • Rationale and background
  • Research question and objectives
  • Study design
  • Setting
  • Subjects and study size, including dropouts
  • Variables and data sources
  • Results
  • Discussion (including, where relevant, an evaluation of the impact of study results on the riskbenefit balance of the product )
  • Marketing authorisation holder
  • Names and affiliations of the principal investigators