Procedures and methods of benefit assessments for medicines in Germany

The Federal Joint Committee (FJC; Gemeinsamer Bundesausschuss,G-BA) defines the health-care elements that are to be reimbursedby sickness funds. To define a directive, the FJC can commissionbenefit assessments, which provide an overview of the scientificevidence regarding the efficacy and benefits of an intervention.This paper describes the operational implementation of the legalrequirements with regard to the benefit assessments of medicines.Such benefit assessments are sometimes referred to as "isolatedbenefit assessments,” to distinguish them from benefitassessments as part of a full economic evaluation. The FJC has the freedom to commission these assessments from anyagency; however, to date the majority have commissioned the Institutefor Quality and Efficiency in Health Care (IQWiG). Nevertheless,the content of this paper applies integrally to any institute commissionedfor such assessments. In this report, "the institute”'is used when the text refers to any of these institutes. The legal framework for benefit assessments is laid out in the GermanSocial Code Book version V (http://www. sozialgesetzbuch.de),Sects. 35b (§ 1), 139a (§ 4-6) and Sect. 139b(§ 3). It is specified that: The institute must guarantee high transparency. The institute must provide appropriate participation of relevantparties for the commission-related development of assessments, andopportunity for comment on all important segments of the assessmentprocedure. The institute has to report on the progress and results of the workat regular intervals. The institute is held to giving the commission to external experts. Based on the legal framework, the institute must guarantee a highprocedural transparency. Transparency of the whole process shouldbe achieved, which is evidenced by clear reporting of proceduresand criteria in all phases undertaken in the benefit assessment.The most important means of enhancing transparency are: 1. To implement a scoping process to support the development ofthe research question. 2. To separate the work of the external experts performing the evidenceassessment from that of the institute formulating recommendations.Therefore, the preliminary report as produced by external expertsneeds to be public, and published separately from any subsequentamendments or (draft-)reports made by the institute, which includesthe institute's recommendations. 3. To implement open peer review by publishing both the commentsof the reviewers and their names. Based on the legal framework, the institute must provide for adequateparticipation of relevant parties. These include organisations representingthe interests of patients; experts of medical, pharmaceutical andhealth economic science and practice; the professional organisationsof pharmacists and pharmaceutical companies; and experts on alternativetherapies. Patients and health care professionals bring in new insightswith respect to research priorities, treatment and outcomes. The relevant parties should be identified and contacted wheneverthe global scope of the assessment has been drafted. Subsequently,the relevant parties should be involved in defining the researchquestion, developing the protocol and commenting on the preliminaryreport. To implement the involvement of relevant parties in definingthe research question a scoping process is suggested. For the otherphases, written comments followed by an oral discussion should beused. Finally, the relevant parties should have the right to appealthe final decision on judicial grounds. None of these steps meanthat the institute would lose any part of its scientific independence. From the relevant sections of the legal framework with respect tothe assessment methods, it can be concluded that: 1. The institute must ensure that the assessment is made in accordancewith internationally recognised standards of evidence-based medicine(EBM). 2. The assessment is conducted in comparison with other medicinesand treatment forms under consideration of the additional therapeuticbenefit for the patients. 3. The minimum criteria for assessing patient benefit are improvementsin the state of health, shortening the duration of illness, extensionof the duration of life, reduction of side effects and improvementsin quality of life.EBM refers to the application of the best available evidence toanswer a research question, which can inform questions about the careof patients. The optimal design, even for effectiveness questions,is not always the randomised, controlled trial (RCT) but dependson the research question and the outcomes of interest. To increasetransparency for each question, the levels of evidence examinedshould be made explicit. There is no empirical evidence to supportthe use of cutoff points with respect to the number of studies beforemaking recommendations. To get the best available evidence for theresearch question(s), all relevant evidence should be consideredfor each question, and the best available evidence should be usedto answer the question. Separate levels of evidence may have tobe used for each outcome. There are many ways in which bias can be introduced in systematicreviews. Some types of bias can be prevented, other types can onlybe reported and, for some, the influence of the bias can be investigated.Reviews must show that potential sources of bias have been dealtwith adequately. Methods used by other agencies that perform benefit assessmentsare useful to interpret the term 'international standards' to whichthe institute must comply. The National Institute for Health andClinical Excellence (NICE) is a good example in this respect. NICEshows that it is possible to have transparent procedures for benefitassessments but that this requires detailed documentation. NICEhas implemented an open procedure with respect to the comments ofreviewers, which makes the procedure transparent. Although the Institutefor Quality and Efficiency in Health Care (IQWiG) in Germany invitescomments on their protocol and preliminary report by posting themon their website, and comments are made public, the individual commentsare not evaluated openly, and therefore it remains uncertain whetheror not they lead to changes in the reports. The participation ofrelevant parties in the assessment process as implemented by NICE guaranteesa process that is transparent to all relevant parties. Transparency of the whole process is assured by clear reporting ofprocedures and criteria in all phases undertaken in the benefitassessment. In a scoping process, a draft scope is commented onfirst in writing and subsequently in the form of a scoping workshop.In this way, all relevant aspects can be heard and included in thefinal scope. The protocol is then developed, followed by evidenceassessment. The methods used should be completely reported to showreaders that the assessment has been performed with scientific rigourand that bias has been prevented where possible. All relevant partiesshould have the opportunity to comment on the draft protocol andthe draft preliminary report. Each comment should be evaluated asto whether or not it will lead to changes, and both the comments andthe evaluation should be made public to ensure transparency of thisprocess. The same procedure should be used for the peer-review phase.Based on the final report of the evidence assessment, the instituteforms recommendations and the FJC appraises the evidence. During the writing of the final report, a separation between the evidenceassessment and the evidenceappraisal phase should be implemented.Ideally, this separation should be legally enforced to prevent anyconfusion about conflict of interests. Such a process guarantees a feasible combination of the legal requirementsfor transparency and involvement of relevant parties with internationalstandards of EBM to ensure that the benefit assessments of medicinesin Germany are performed according to the highest standards.