Source: http://www.healtheconomicsblog.com/2011/01/new-chapter-of-procedural-rules-of_26.html
Timestamp: 2019-04-22 11:17:35+00:00

Document:
(1) On the basis of the Regulation for Pharmaceutical Benefit Assessments this chapter regulates the procedure of the benefit assessment of pharmaceuticals with new active ingredients eligible for reimbursement pursuant to Section 35a para. 1 and para. 6 of the German Social Code Book V, especially the advice, the requirements for required evidence (dossier) for proof of benefit, the procedure for the hearings and the implementation of the benefit assessment into the Pharmaceutical Guideline.
6. For which the Federal Joint Committee has decided upon a benefit assessment with a time limit, as soon as this time limit has expired.
(3) The provisions of chapter 4 of the Procedural Rules are not affected by these provisions.
at least one new active ingredient, shall be deemed to be pharmaceuticals in terms of clause 1.
 The indication is transferred into another therapeutic area (treatment, diagnosis, prophylaxis).
(1) The benefit of a pharmaceutical is the patient-relevant, therapeutic effect, particularly with regard to an improvement in the state of health, the shortening of the duration of illness, the extension of survival, the reduction of side effects or an improvement in the quality of life.
(2) The additional benefit of a pharmaceutical is a benefit in terms of paragraph 1 that is quantitatively or qualitatively greater than the benefit provided by the appropriate comparative therapy.
5. Assessment of the additional benefit by the Federal Joint Committee.
(3) The subcommittee shall hold discussions on the basis of the report of the working group and shall submit the results of its assessment and a draft decision to the plenary.
(1) The additional benefit must be proven by the pharmaceutical entrepreneur in the dossier pursuant to Section 9. The Federal Joint Committee is under no obligation to officially investigate.
(2) For pharmaceuticals with new active ingredients that are eligible for reimbursement and are pharmacologically-therapeutically comparable to reference price drugs, the additional medical benefit must be proven as a therapeutic improvement in accordance with Section 35 para. 1b clause 1 to 5 of the of the German Social Code Book V. Proof of a therapeutic improvement is rendered based on the summary of product characteristics and based on an assessment of clinical trials according to the international standards of evidence-based medicine. Priority consideration must be given to clinical studies, especially direct comparative studies with other pharmaceuticals of this reference price group with patient-relevant endpoints, especially mortality, morbidity and quality of life.
justification. In addition the pharmaceutical entrepreneur shall demonstrate to what extent the evidence submitted by him as the best available evidence is appropriate for proof of an additional benefit. The recognition of the additional benefit on the basis of materials of a lower level of evidence will require a grade of justification proportional to the deviation of level of evidence I.
(4) The probability and extent of an additional benefit must be presented in the dossier. In doing so, the informative value of the evidence must be indicated. Regarding the probability the extent of certainty regarding the statement on the existence of an additional benefit (certainty of results) has to be explained. The information regarding the informative value of results shall be presented in reference to the number of patients and to the magnitude of the additional benefit as well.
(5) For pharmaceuticals according to paragraph 3, the additional benefit compared to the appropriate comparative therapy is determined as an improvement in influencing patient-relevant endpoints to produce a benefit pursuant to Section 3 para. 1. For proof of the additional benefit randomized, blinded and controlled direct comparative studies shall be preferably considered the methodology of which a corresponding are corresponding to the international standards and to the evidence-based medicine. These studies should have been conducted with populations or under conditions which are representative and relevant for the usual treatment situation and in comparison to an appropriate comparative therapy according to Section 6. If no direct comparative studies for the new pharmaceutical and the appropriate comparative therapy are available or said studies do not allow sufficient conclusions regarding an additional benefit, available clinical studies for the appropriate comparative therapy can be consulted, preferably randomized, blinded and controlled studies, if they are appropriate for an indirect comparison to the new pharmaceutical with the new active ingredients and thus are appropriate for the proof of the additional benefit by indirect comparison. If it is not possible that valid data on patient-relevant endpoints are available at the time of evaluation, the assessment is made based on the best available evidence in consideration of the study quality and the probability of a proven additional benefit is indicated.
7. V Associative observations, pathophysiological considerations, descriptive presentations, individual case reports, opinions of acknowledged experts not backed up by studies, consensus conferences and reports of expert committees.
6. The benefit of the pharmaceutical to be assessed is smaller than the benefit of the appropriate comparative therapy.
(1) An appropriate comparative therapy is the therapy whose benefit is compared to the benefit of a pharmaceutical with new active ingredients for the benefit assessment in accordance with Section 35a of the of the German Social Code Book V.
(2) The appropriate comparative therapy must regularly be determined according to benchmarks resulting from the international standards of evidence-based medicine. Among several alternatives, the more economical therapy must be chosen, preferably a therapy that is subject to a reference price.
1. In cases where the application of a pharmaceutical is eligible as a comparative therapy as a rule the pharmaceutical must be authorized for the therapeutic indication.
2. In cases where a non-pharmaceutical treatment is eligible as a comparative therapy this treatment must be suitable to be applied within the framework of the statutory health insurance.
3. As comparative therapies those applications of pharmaceuticals or non-pharmaceutical treatments should be chosen whose patient-relevant benefit has already been confirmed by the Federal Joint Committee.
4. The comparative therapy shall be part of the appropriate therapy in the therapeutic area according to the generally acknowledged state of medical knowledge.
5. In case of several alternative therapies the more economic one should be chosen, preferably a therapy for which a reference price has been set.
(4) For pharmaceuticals of a single substance category, in consideration of para. 3 the same appropriate comparative therapy must be used in order to ensure a uniform assessment. The appropriate comparative therapy must also be suitable for assessments of pharmaceuticals launched prior to January 1, 2011, prompted by the Federal Joint Committee pursuant to Section 35a para. 6 of the of the German Social Code Book V.
request of an advice the form according to annex I (request form) shall be used. In the request form (annex I) the questions to be discussed during the advice shall be submitted in German. The pharmaceutical entrepreneur shall submit to the Federal Joint Committee the materials and information that are significant for the compilation of the dossier for the benefit assessment and that are available at that point in time in German or in English. The consultation is conducted within eight weeks after submission of the materials. If the pharmaceutical entrepreneur does not submit the materials needed for the advice the Federal Joint Committee may refrain from an advice. The advice is performed by the office of the Federal Joint Committee unless a different decision is made. The advice may take place before the start of the phase III studies and with the participation of the Federal Institute for Drugs and Medical Devices or the Paul Ehrlich Institute.
(2) The information sent as part of the advice must be treated confidentially. The pharmaceutical entrepreneur will receive a transcript of the advice. The Federal Joint Committee can conclude agreements with the pharmaceutical entrepreneur in this respect. The information given by the Federal Joint Committee during an advice on topics according to para. 1 clause 1 is non-binding.
(3) For benefit assessments pursuant to Section 16, an advice must be offered before the Federal Joint Committee requests the pharmaceutical entrepreneur to submit a dossier. The advice will be given in German.
(4) For the advice fees will be collected. Details on the amount of the fees are set in the fee regulation.
1. At the time of the initial launch, for pharmaceuticals with new active ingredients that are launched for the first time from January 1, 2011 on. The inclusion of the pharmaceutical into the big German Specialty-list (so called. „Lauer-Taxe“) is deemed as the relevant time for the first marketing of the pharmaceutical.
2. Within four weeks from authorization of the new therapeutic indication, for pharmaceuticals that receive a new therapeutic indication pursuant to Section 2 para. 2, if a benefit assessment in accordance with these Procedural Rules was conducted for the pharmaceutical, or within four weeks of the notification of the pharmaceutical entrepreneur regarding approval of a variation of type II according to Annex II No. 2 Letter (a) of Commission Regulation (EC) No 1234/2008.
6. Three months after request by the Federal Joint Committee for pharmaceuticals according to §§ 12-15.
6. The requirement for a quality-assured application.
(2) For the compilation of the materials the dossier template in annex II shall be used. The data pursuant to para. 1 and 4 to 8 shall be structured and submitted according the requirements given in modules 1 to 5. Modules 1 to 4 contain the basics supporting the assessment and these modules will be completely published on the website of the Federal Joint Committee. Documents containing business and trade secrets have to be indicated by the pharmaceutical entrepreneur in module 5.
(3) Even if the pharmaceutical entrepreneur contradicts the publication of documents in module 5 referring to Section 10 he shall ensure that all information regarding the methodology and results of the studies is completely submitted for publication in the dossier in modules 1 to 4 according to the requirements of para. 2 clause 2. If the dossier does not fulfill these requirements proof of the additional benefit can be deemed as not having been made.
trial protocols and the assessment report of the regulatory agency, as well as all studies transmitted to the regulatory agency. Furthermore, all results, study reports and trial protocols for studies on the pharmaceutical are transmitted that were sponsored by the pharmaceutical entrepreneur, as well as all available information on ongoing or canceled studies involving the pharmaceutical, which were sponsored by the pharmaceutical entrepreneur or in which said entrepreneur participated financially in some other way, and corresponding information on third-party studies, if these are available.
(5) The dossier should also include the marketing authorization number, the date of marketing authorization, the marketing authorization holder, the central pharmaceutical number (PZN), the assignment to the anatomical-therapeutic-chemical (ATC) classification and the name of the pharmaceutical.
(6) For the appropriate comparative therapy, the pharmaceutical entrepreneur transmits all available results of clinical trials in the dossier, including study protocols that are appropriate for making findings on the additional benefit of the pharmaceutical to be assessed. If no clinical studies are available for a direct comparison with the pharmaceutical to be assessed or if they do not allow any sufficient conclusions regarding additional benefit, indirect comparisons can be submitted in the dossier.
(7) The pharmaceutical entrepreneur must indicate the costs for statutory health insurance measured by the pharmacy retail price and the costs actually incurred by the health funds. The costs must be indicated both for the pharmaceutical to be assessed and for the appropriate comparative therapy. Relevant are the direct costs for statutory health insurance over a certain time period. If the pharmaceuticals are used in accordance with the summary of product characteristics or the package leaflet and there are regularly differences in the necessary utilization of medical care or in the prescription of other services between the drug to be assessed and the appropriate comparative therapy, the associated cost differences must be considered for determining the costs actually incurred by the health funds.
(8) The dossier shall contain in module 1 a summary of the essential conclusions which shall be the basis for an agreement pursuant to Section 130b of the German Social Code Book V.
(1) The dossier is published on the website of the Federal Joint Committee simultaneously with the benefit assessment according to Section 18 para. 4, unless this is precluded by business and trade secrets, the protection of intellectual property or data privacy. The publication shall include the fundamentals on which the assessment is based.
(2) The pharmaceutical entrepreneur shall indicate business and trade secrets in the dossier; this does not affect Section 9 para 2 and 3. This indication must not be in conflict with the obligation to disclose study results.
(3) The Federal Joint Committee can settle the details based on agreements with the relevant trade associations of the pharmaceutical industry and with the pharmaceutical entrepreneurs.
(1) Das Dossier ist spätestens zu den in § 8 bestimmten Zeitpunkten zu übermitteln. The Federal Joint Committee must only take documents submitted in due time into consideration. Documents from the regulatory agencies that were not yet available to the pharmaceutical entrepreneur at the time relevant for submission must be considered as long as the benefit assessment is not delayed as a result.
(2) The pharmaceutical entrepreneur may also transmit the dossier to the Federal Joint Committee before the times mentioned in Section 8. If the pharmaceutical entrepreneur submits the dossier to the Federal Joint Committee three weeks before the respective time, the office of the Federal Joint Committee will conduct a formal preliminary examination of the dossier for completeness validation. If the dossier is incomplete, the office of the Federal Joint Committee shall inform the pharmaceutical entrepreneur typically within two weeks what additional information is necessary. This does not affect the examination of the dossier in terms of content.
(3) The Federal Joint Committee shall request from the respective pharmaceutical entrepreneur the timely and complete submission of the dossier. The Federal Joint Committee may also request from the pharmaceutical entrepreneur the timely submission of a complete dossier after an advice pursuant to Section 7.
1. The medical additional benefit pursuant to Section 35a para. 1 clause 3 No. 2 and 3 of the German Social Code Book V is deemed to be proved by the marketing authorization; evidence according to Section 5 para. 1 to 6 need not be submitted. This does not affect Section 5 para. 7. The extent of the additional benefit shall be demonstrated for the number of patients and patient groups for whom a therapeutically relevant additional benefit exists.
2. If the turnover of the orphan drug made with statutory health insurance measured in retail pharmacy prices including value added tax within the last 12 months exceeds 50 million Euros the pharmaceutical entrepreneur shall transmit evidence pursuant to Section 5 para. 1 to 6 within 3 months after the request of the Federal Joint Committee and with this evidence he shall demonstrate the additional benefit compared to the appropriate comparative therapy. The turnover shall be calculated on the basis of the information pursuant to Section 84 para. 5 clause 4 of the German Social Code Book V.
(1) Following the request of its members or of the organisations and institutions mentionend in Section 139b para. 1 clause 2 of the German Social Code Book V due to new scientific findings the Federal Joint Committee may decide on a further benefit assessment no earlier than one year after the decision regarding the benefit assessment pursuant to Section 20 for a pharmaceutical which has been assessed according to the requirements of this chapter. This is also valid whenn the therapeutic area of the pharmaceutical has been restricted by the competent regulatory agency. Section 16 para. 2 applies accordingly.
(2) Together with the delivery of the decision the pharmaceutical entrepreneur shall be informed on the reasons for the benefit assessment.
(1) The pharmaceutical entrepreneur can apply for a further assessment at the Federal Joint Commitee no earlier than one year after publication of the decision pursuant to Section 20, in case that he demonstrates the need for a further assessment due to new scientific findings.
(2) The Federal Joint Committee decides on the application within 3 months. If the Federal Joint Committee came to the conclusion that the application is justified it shall request the pharmaceutical entrepreneur to transmit the necessary evidence according to the requirements of this chapter. The dossier shall be submitted by the pharmaceutical entrepreneur to the Federal Joint Committee within 3 months after the delivery of the decision.
of the pharmaceutical according to the requirements of this chapter (especially sections 11 and 13) if it can be expected that this pharmaceutical will cause only insignificant expenditures for statutory health insurance. The assessment of the insignificance is made on the basis of information on the expected costs for the sick funds in the meaning of Section 9 para. 8 as well as the expected turnover of the pharmaceutical with statutory health insurance. As long as the expected expenditures do not exceed an amount of 1.000.000 Euros within 12 calendar months these are classified as insignificant.
(2) The pharmaceutical entrepreneur shall demonstrate the reasons for the waiver application according to para. 1. For the assessement of the insignificance of the expenditures he shall submit sufficient information for the Federal Joint Committee.
(3) The Federal Joint Committee decides on the application within 8 weeks.
(4) In case the turnover of the pharmaceutical with statutory health insurance at pharmacy retail prices exceeds 1.000.000 Euros within 12 calendar months the pharmaceutical entrepreneur shall transmit evidence pursuant to Section 5 para. 1 to 6 within 3 months after the request by the Federal Joint Committee and with this evidence he shall demonstrate the additional benefit compared to the appropriate comparative therapy. The turnover shall be calculated on the basis of the information according to Section 84 para. 5 clause 4 of the German Social Code Book V.
(1) For already authorized and marketed pharmaceuticals the Federal Joint Committee may decide on the conduct of a benefit assessment according to the requirements of this chapter, following a request of its members or of the organisations and institutions mentioned in Section 139b para. 1 clause 2 of the German Social Code Book V. As a priority these pharmaceuticals will be assessed which are important for the supply or which compete with pharmaceuticals for which a decision according to Section 20 exists.
(2) The dossier shall be submitted to the Federal Joint Committee by the pharmaceutical entrepreneur within three months after delivery of the decision.
(2) The Federal Joint Committee decides whether to conduct the benefit assessment on its own or to commission the Institute for Quality and Efficiency in Health Care (IQWiG) or a third party.
2. The finalised benefit assessment shall be transferred to the Federal Joint Committee two working days before the expiry of the relevant date for publication according to Section 18 para. 4.
(1) The benefit assessment examines if an additional benefit compared to the appropriate comparative therapy has been proven for the pharmaceutical, what additional benefit has been proven, to what extent and for which patient groups, how the available evidence must be rated and with what probability each proof has been rendered. The benefit assessment is conducted on the basis of the dossier.
(2) The benefit assessment examines the validity and completeness of the information in the dossier. The materials are assessed with regard to their planning, implementation and evaluation quality in terms of their informative value for the probability and extent of an additional benefit and regarding their information on therapy costs. The benefit assessment also contains a summary of the essential conclusions as a rating of the information in the dossier according to Section 9 para. 1. The benchmark for the assessment is the generally acknowledged state of medical knowledge. Basis of the assessment are the international standards of evidence-based medicine and health economics.
(3) For the initial evaluation pursuant to Section 35a of the of the German Social Code Book V at the time of market launch, the assessment of a pharmaceutical with new active ingredients must be based on marketing authorization studies. If these marketing authorization studies are insufficient, the Federal Joint Committee can demand additional proof.
in consideration of the study quality and the probability of a proven additional benefit is indicated. If valid data on patient-relevant endpoints are necessary to prove an additional benefit, a deadline can be determined by the Federal Joint Committee by which the data should be submitted at the latest.
(5) The benefit assessment must be completed no later than three months after the date that is relevant pursuant to Section 8 and be published on the internet.
(1) By publishing the benefit assessment on the website of the Federal Joint Committee the experts of medical and pharmaceutical science and practice as well as the leading organisations of the pharmaceutical companies created for the representation of their economic interests, the concerned pharmaceutical companies, the representatives of the pharmacists and the leading overarching associations of the medical societies of the special therapies on the federal level will have the opportunity to comment in writing on the benefit assessment of the pharmaceutical by using the templates in annex III. The commenting period will be 3 weeks.
2. Give comments on the possibilities of the decision making of the benefit assessment pursuant to Section 92 para. 1 clause 2 no. 6 of the German Social Code Book V according to the principles laid down in these Procedural Rules.
(3) The written and oral comments pursuant to para. 1 and 2 will be considered in the decision on the decision making on the benefit assessment according to Section 92 para. 1 clause 2 no. 6 of the German Social Code Book V. For the evaluation of the comments chapter 1 Section 10 para. 3 of the Procedural Rules shall apply.
(1) The Federal Joint Committee decides on the benefit assessment within three months from publication. The decision will be published on the internet. It shall be part of the Pharmaceutical Guideline pursuant to Section 92 para. 1 clause 2 no. 6 of the German Social Code Book V and is published in the Federal Gazette. Section 94 para. 1 of the German Social Code Book V does not apply.
(2) For all pharmaceuticals with this active ingredient, the decision forms the basis for negotiations regarding reimbursement amounts pursuant to Section 130b of the of the German Social Code Book V and for the stipulation of requirements pertaining to the suitability, quality and economic efficiency of the prescription as well as for recognition as a practice specialty or for the assignment of pharmaceuticals without additional benefit to a reference price group in accordance with Section 35 of the of the German Social Code Book V.
2. On the number of patients respectively on the differentiation of patient groups eligible for the treatment.
4. On the therapy costs also compared to the appropriate comparative therapy.
1. Pharmaceuticals with a new active ingredient which are pharmacologically-therapeutically comparable to reference price drugs according to Section 35 para. 1 clause 2 no. 2 of the German Social Code Book V for which a reference price group exists are assigned to this reference price group by the decision.
Social Code Book V is possible the Federal Joint Committee states this in the decision according to Section 35 para. 3 of the German Social Code Book V.
3. In all other cases the Federal Joint Committee examines whether the creation of a reference price group in accordance with Section 35 para. 1 clause 2 no. 3 of the German Social Code Book V and Chapter 4 Section 20 of the Procedural Rules is possible.
If the benefit assessment comes to the conclusion that an additional benefit for the pharmaceutical is proven according to the generally acknowledged state of medical knowledge, the Federal Joint Committee will state this in its decision pursuant to Section 35a para. 3 of the German Social Code Book V in the Pharmaceutical Guideline together with information on the extent of the additional benefit.
Thanks a lot ! very useful hint for my current project.
Wondering if others will follow the German regulator?

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