Appendixes
ANNEX IISupplementary provisions
ANNEX II TEMPLATE FOR THE JOINT CLINICAL ASSESSMENT REPORT The report shall follow international standards of evidence-based medicine and take into account, if available, the methodological guidance, adopted by the HTACG pursuant to Article 3(7), point (d), of the HTAR. List of abbreviations The following list presents suggestions for abbreviations. It may be adapted to the report. Abbreviation Meaning ATC Anatomical Therapeutic Chemical ATMP Advanced Therapy Medicinal Product CSR Clinical Study Report EEA European Economic Area EMA European Medicines Agency EU European Union HTA Health Technology Assessment HTACG Member State Coordination Group on Health Technology Assessment HTAR Regulation (EU) 2021/2282 of the European Parliament and of the Council of 15 December 2021 on health technology assessment amending Directive 2011/24/EU HTD Health Technology Developer JCA Joint Clinical Assessment JSC Joint Scientific Consultation PICO A set of parameters for the joint clinical assessment in terms of: Patient Population – Intervention(s) – Comparator(s) – Health Outcomes PRIME Priority Medicines scheme by the European Medicines Agency RCT Randomised Controlled Trial RoB Risk of Bias SmPC Summary of Product Characteristics etc. Table of contents List of tables 1. General information on the JCA This section shall provide: — information on the assessor and co-assessor, — an overview of the procedural steps and their dates, — information on the involvement of patients, clinical experts and other relevant experts, as well as on the input received from patient organisations, healthcare professional organisations and clinical and learned societies. The input from experts and stakeholders shall be provided in Appendix A, — information on previous JSC under the HTAR. 2. Background 2.1. Overview of the medical condition This section shall provide: — a summary of the medical condition, including the symptoms and the burden and natural progression of the medical condition, its prevalence or incidence in the EEA States in which the HTAR is applicable, as available, — a brief description of the target patient population and its characteristics reflected in the assessment scope as set out pursuant to Article 8(6) of the HTAR, — a brief description of the care pathway for the medical condition and whether it varies substantially between the EEA States in which the HTAR is applicable, as well as, if relevant, for different stages and/or subtypes or sub-populations of the medical condition. 2.2. Characterisation of the medicinal product 2.2.1. Characteristics of the medicinal product This section shall describe characteristics of the medicinal product under assessment (‘the medicinal product’) and report the following information: — proprietary name, — active substance(s), — pharmaceutical formulation(s), — therapeutic indication, — marketing authorisation holder, — mechanism of action, — ATC code where already assigned. 2.2.2. Requirements/instructions for use This section shall include a description of the methods of administration, dosing of the medicinal product and duration of treatment. 2.2.3. Regulatory status of the medicinal product This section shall describe the regulatory information on the medicinal product and provide details of the procedural pathway of the medicinal product in the EU, such as orphan medicinal product designation, conditional marketing authorisation with any specific obligations of the conditional marketing authorisation, ATMP or PRIME. It shall also provide details of ongoing or planned early access/compassionate use programs in the EEA. When appropriate links to SmPC shall be inserted for details of other licensed therapeutic indications and to the dossier for further regulatory information. 3. Assessment scope This section shall reproduce the assessment scope as set out pursuant to Article 8(6) of the HTAR. 4. Results The results presented in this section shall follow international standards of evidence-based medicine and take into account, if available, the methodological guidance adopted by the HTACG pursuant to Article 3(7), point (d), of the HTAR. Any deviations shall be described and justified. 4.1. Information retrieval This section shall include: — a description of the information retrieval performed by the HTD, — an assessment of the appropriateness of the sources and the search strategies of the HTD. It shall provide the date of the list of the studies, performed or sponsored by the HTD or by third parties, referred to in Annex I, point (b), of the HTAR, as well as the date of the last searches for the medicinal product and the comparator(s) in bibliographic databases and in study registries and study results registries (clinical trial databases). Detailed information shall be provided in Appendix B. 4.1.1. Resulting list of included studies overall and by PICO This section shall provide in tabular format: — an overview of all included studies and the associated references for these studies overall and by PICO, — the list of studies included by the HTD which were excluded within the assessment, with a justification for their exclusion. 4.2. Characteristics of included studies and RoB 4.2.1. Included studies This section shall provide for the studies included in the assessment: — information on the study design (e.g. on randomisation, blinding, or parallel observation studies, and the key inclusion and exclusion criteria), — information on enrolled study populations (e.g. diagnosis, general severity of medical condition, and line of therapy), — characteristics of the study interventions, — information on the course of the study (e.g. planned and actual follow-up times per outcome), — information on the study duration. 4.2.2. RoB This section shall describe the assessment of RoB at the study level taking into account, if available, the methodological guidance adopted by the HTACG pursuant to Article 3(7), point (d), of the HTAR. 4.3. Study results on relative effectiveness and relative safety The results on relative effectiveness and relative safety shall be presented according to the assessment scope as set out pursuant to Article 8(6) of the HTAR, per PICO. An assessment of the degree of certainty of the relative effectiveness and relative safety, considering the strengths and limitations of the available evidence shall be performed taking into account, if available, the methodological guidance adopted by the HTACG pursuant to Article 3(7), point (d), of the HTAR. 4.3.1. Results for patient population <Z-1> This section shall discuss to which extent the included patient populations and/or comparator(s) per study cover the relevant patient population/comparator(s) according to the assessment scope as set out pursuant to Article 8(6) of the HTAR. For each patient population specified in PICO(s), a separate section shall be provided. Within this section, the results for all PICO(s) addressing this patient population shall be presented in sub-sections. 4.3.1.1. Patient characteristics This section shall present patient characteristics from all studies covering the relevant patient population included in any of PICO(s) addressing this patient population. 4.3.1.2. Evidence synthesis methods This section shall briefly describe, when applicable, the evidence synthesis methods used by the HTD, including the associated strengths and limitations, and any factors arising from these methods and their application which may affect the certainty of the evidence taking into account, if available, the methodological guidance adopted by the HTACG pursuant to Article 3(7), point (d), of the HTAR. 4.3.1.3. Health outcome results for PICO <1> and uncertainties in the results Within the given patient population, results on health outcomes describing relative effectiveness and relative safety shall be described by PICO. The section shall start from describing and justifying the choice of evidence (type of comparison) submitted to address the given PICO <1>. The section shall present an overview of the available outcomes requested in the assessment scope per study. Results on relative effectiveness and relative safety (i.e. the relative effects of the medicinal product versus the comparator) shall include the results from all individual studies, as well as any quantitative syntheses of results, e.g. from meta-analyses. The results of the analyses of each of the presented outcomes shall be described briefly. The description shall address any issues affecting the degree of uncertainty of the relative effects taking into account, if available, the methodological guidance adopted by the HTACG pursuant to Article 3(7), point (d), of the HTAR. For any additional PICO question related to a given patient population, a new sub-section presenting the results in terms of health outcomes for this PICO question shall be added. 4.3.2. Results of the main study from the clinical development programme of the medicinal product (if not addressed by any of PICO(s)) 4.3.2.1. Characteristics of the pivotal study 4.3.2.2. Patient characteristics 4.3.2.3. Health outcome results of the pivotal study and uncertainties in the results 5. References Appendixes Appendix A. Input from experts and stakeholders Appendix B. Assessment of information retrieval Appendix C. Additional study information and data, including uncertainties in the results.