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CHWERPUNKT

ecision making in Germany: Is healthconomic evaluation as a supporting tool aleeping beauty?osten-Nutzen-Bewertung zur Unterstützung derntscheidungsfindung in Deutschland: im Dornröschenschlaf?

ndreas Gerber-Grotea,∗, Frank Gerd Sandmanna, Min Zhoua,orinna ten Thorena, Anja Schwalma, Carolin Weigela,hristiane Balga, Alexander Menscha, Sarah Mostardta,strid Seidl a, Stefan K. Lhachimia,b

Institute for Quality and Efficiency in Health Care (IQWiG), Cologne, GermanyResearch Group for Evidence Based Public Health, Leibniz Institute for Prevention Research andpidemiology, Bremen, Germany & Institute for Public Health and Nursing Research, University of Bremen,remen, Germany (as of April 1st, 2014)

ubmitted/eingegangen 7 April 2014; revised/überarbeitet 25 June 2014; accepted/akzeptiert 25 June 2014

KEYWORDSHealth economicevaluation;Germany;IQWiG;efficiency frontier;reimbursement;decision making

Summary For many years, the legal situation within the statutory health insurance (SHI) sys-tem in Germany has allowed for health economic evaluations. There are various reasons whyhealth economic evaluations have played virtually no role in decision making until now: to beginwith, a method for the evaluation of the relation between benefits and costs which needed to bein accordance with the legal requirements had to be developed, the outcome of which was theefficiency frontier approach. Subsequent health care reforms have led to changing objectivesand strategies. Currently, price negotiations of newly launched drugs are based on an early ben-efit assessment of dossiers submitted by pharmaceutical manufacturers. Other reasons mightbe the presently very comfortable financial situation of the statutory health insurance system

as well as a historically grown societal fear and discomfort towards what is perceived to be arationing of medicinal products. For the time being, it remains open how long the German healthcare system can afford to continue neglecting the benefits of health economic evaluations fordrug and non-drug interventions, and when it will be time to wake this sleeping beauty.

∗ Corresponding author: PD Dr. med. Andreas Gerber-Grote, Dipl.-Theol. (ev.), MA, MSc, Ressortleiter Gesundheitökonomie / Head ofDepartment Health Economics, Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen (IQWiG) / Institute for Quality andEfficiency in Health Care (IQWiG), Im Mediapark 8, 50670 Köln, Germany. Tel.: +49-221/35685-65; fax: +49-221/35685-1.E-Mails: andreas.gerber@iqwig.de, andreas gerber@hotmail.com (A. Gerber-Grote).

ttp://dx.doi.org/10.1016/j.zefq.2014.06.018865-9217/

Decision making in Germany: Is health economic evaluation as a supporting tool a sleeping beauty? 391

SCHLÜSSELWÖRTERKosten-Nutzen-Bewertung;Deutschland;IQWiG;Effizienzgrenze;Erstattung;Entscheidungsfindung

Zusammenfassung Nach vorherrschendem Recht sind Kosten-Nutzen-Bewertungen im Systemder gesetzlichen Krankenversicherung in Deutschland explizit bereits seit Jahren vorgese-hen. Die Ursachen dafür, dass sie bisher in der Entscheidungsfindung nicht genutzt wurden,sind vielfältig: Zunächst musste eine Methode für die Bewertung von Verhältnissen zwischenNutzen und Kosten entwickelt werden, die im Einklang mit der deutschen Gesetzgebung steht(das Effizienzgrenzen-Konzept). Danach brachten Gesundheitsreformen veränderte Zielset-zungen und Herangehensweisen mit sich. So ist gegenwärtig eine frühe Nutzenbewertungvon neuen Arzneimitteln basierend auf den von pharmazeutischen Unternehmen einge-reichten Dossiers Grundlage für Preisverhandlungen. Weitere Gründe sind unter anderem in deraktuell guten finanziellen Lage des deutschen Gesundheitssystems sowie historisch gewachse-nen gesellschaftlichen Überzeugungen wie beispielsweise der Angst vor Rationierung zu suchen.Gegenwärtig ist offen, wie lange die Entscheidungsträger im deutschen Gesundheitssystem aufKosten-Nutzen-Bewertungen verzichten wollen, die transparent Informationen zur Preisgestal-tung von Arzneimitteln und nicht-medikamentösen Verfahren liefern können, und wann es an

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Introduction

As of early 2014, the health economic evaluation has beena tool of last resort and practically plays no role in decision-making in the German statutory health insurance (SHI)system, which serves about 90% of the German popula-tion [1]. While the Institute for Quality and Efficiency inHealth Care (Institut für Qualität und Wirtschaftlichkeitim Gesundheitswesen = IQWiG), which was founded in 2004,in its very name contains a reference to efficiency (=Wirtschaftlichkeit), it was not commissioned with anyhealth economic evaluation until 2009. Even though drugswere explicitly exempted from health economic evalua-tion until 2007, the law previously allowed commissioningthe IQWiG with a combination of a health economic eval-uation and a full benefit assessment of other kinds ofinterventions.

So why does the health economic evaluation not havea more prominent role in the decision-making processand has remained a sleeping beauty in the German SHIsystem? Before we attempt to answer this important ques-tion we would like to present an overview of how healtheconomic evaluation is utilized in the decision-making pro-cess in the German health care system. This is doneagainst the background of the historic development ofhealth economic evaluation and the current legal and pro-cedural situation, especially for new drugs entering themarket.

History of health economic evaluation since2004

The German SHI system is based on one basic legal docu-ment: The German Social Code Book V (Sozialgesetzbuch,SGB V). A history of the relevant paragraphs sheds lighton the intricacies of health economic evaluation in Ger-many. When IQWiG, an independent scientific HTA bodyproviding the SHI system and its decision-makers with sci-

entifically sound information on interventions in the healthcare system, was founded in 2004 by the SHI Moderniza-tion Act (GKV-Modernisierungsgesetz) [2], the institute wasassigned to assess the benefit and harm of drugs and then

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eliver this information to the Federal Joint CommitteeFJC = Gemeinsamer Bundesausschuss), the decision-makingody in the German SHI system of self-governance. With thisnformation, the FJC was then able to tailor reference priceroups for chemical entities with a similar benefit and harm,.g. statins. After a market access of new drugs, a fourthurdle, however, was meant to be avoided. This point wasirrored in the legal text of the Social Code Book V: Drugsere explicitly exempted from health economic evaluation

see §139a sec. 3 in the 2003 version) [2,p.2223]. This legaltipulation was the result of a compromise with the phar-aceutical industry.Under the pressure of fast rising prices of pharmaceut-

cals and patented drugs in particular [3], the coalitionovernment of Christian and Social Democrats decidedo come to some kind of price cap regulation. In §35bf the health care reform of 2007 (SHI Act to Promoteompetition, GKV-Wettbewerbsstärkungsgesetz) [4], healthconomic evaluation was therefore explicitly introducedith the goal of setting maximum reimbursement prices forrugs. This was to be attained by performing a full benefitssessment and under the condition that an added benefitas proven and attested by IQWiG. In addition, §139a sec.specified that drug costs could also become the subject ofn assessment by IQWiG.

With a new coalition government of Christian Democratsnd Liberal Democrats coming into power in late 2009, thect on the Reform of the Market for Medicinal ProductsGesetz zur Neuordnung des Arzneimittelmarktes, AMNOG)as passed and came into effect on January, 1st 2011 [5—7].t this time, §35b in the Social Code Book V was altered: 1)

QWiG was no longer to be responsible for delivering a max-mum reimbursement price. The legal text, though unclearbout what exactly the outcome of a health economic eval-ation should encompass, alludes in a more general wayo a health economic evaluation providing information tossist the FJC in the decision about the appropriatenessAngemessenheit) and affordability (Zumutbarkeit) of therice of a drug. 2) Procedural changes now required—–in case

health economic evaluation is requested—–the submission

f a dossier (containing a health economic evaluation) by theanufacturer and a subsequent health economic evaluationy IQWiG (please also see the section labelled ‘‘Current legal

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ituation: Process of health economic evaluation accord-ng to AMNOG’’). According to §139a, the possibility ofonducting health economic evaluations for drug and non-rug interventions remained untouched.

bstacles and challenges during thentroduction of health economic evaluation

bstacles and challenges during the introduction of a healthconomic evaluation can be categorized into cultural, his-orical, and ethical. Culturally, a reluctance to explicitlyecide on a fixed maximum willingness-to-pay and subse-uent reimbursable costs of an intervention is a commonlyhared view. Historical experience with the Nazi regimend its way of treating certain parts of the populations unworthy subjects also seems to feed into the cur-ent prudence in terms of decision-making on the basisf health economic evaluation [8]. Some of these aspectsere discussed in an expertise by the German Ethics Coun-il (Deutscher Ethikrat) in early 2011 [9]. As the Socialode Book refers to the principle of solidarity (Solidarität-prinzip) it ‘‘asserts that anyone who needs a treatment isntitled to receive it. This has been made particularly cleary a high court decision in 2005 [10] involving an appealy a patient suffering from Duchenne muscular dystrophyho was denied an unconventional bioresonance treatmenty his statutory health insurance (SHI) fund. The courtecreed that treatment in the case of a life-threatening dis-ase is an essential part of health care and that SHI funds

ust pay for it.’’ [11,p.9]. Finally, it may not be surpris-

ng that there is no general threshold for the incrementalost-effectiveness ratio both for cultural and legal reasons9,12].

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Table 1 German guidelines for health economic evaluations.*

Guideline item Explanation of the requirements for health

Study perspective Perspective of Statutory Health Insurance ibe undertaken (e.g. societal, separate braninsurance, pension insurance) if commissio

Comparator All therapeutic alternatives (pharmaceuticindication.

Analysis technique Cost-effectiveness analysis with the efficie(outcomes), QALYs or other modes of aggretreatment path should be displayed to guid

Time horizon Depending on the nature of the disease, buCosting methods Primarily direct costs (see study perspectiv

perspective or scenario.Quality of life methods No preferred method. An overall caveat agModelling techniques Transparent reporting of model structure,

electronic version are requested.Incremental methods Incremental in form of the efficiency frontDiscounting Identical constant rates of 3% in the base caSensitivity analysis Deterministic, probabilistic and scenario anExpert panels May be used in case of lack of input param

composition, questions etc. is mandatory.

QALY: quality-adjusted life year.* As of IQWiG’s methods version 4.2 published for consultation on Jun

A. Gerber-Grote et al.

QWiG’s methods of health economicvaluation: The efficiency frontier approach

n a difficult time regarding health economic evaluation inermany, IQWiG, with the help of external experts, com-ents from stakeholders and IQWiG’s Scientific Advisoryoard, developed its methods (see Table 1). In 2009, thenalized version of IQWiG’s methods of conducting andssessing a health economic evaluation were published and,ue to changes imposed by AMNOG, updates are publishedor consultation [13]. Nonetheless, even the 2009 versionoes not contradict the aim of a health economic evaluations established with AMNOG: making recommendations aboutnterventions’ appropriate reimbursement prices [14,15].lease note: the methods for health economic evaluationeveloped by IQWiG were at no time limited to drugs onlyut equally apply to non-drug interventions.

Recommending reimbursement prices diverges from thenternational aim to determine cost-effectiveness in ordero allocate resources across diseases [16]. Although oneight debate whether by implementing such an approach,

he opportunity costs are adequately reflected by policyakers, the efficiency frontier approach in particular was

onstructed to provide a solution to the legal require-ents (no legally acceptable cost-effectiveness threshold

as yet been available for Germany). The obstacles andhe controversial debate, particularly relating to thefficiency frontier approach, have been laid out elsewhere15,17—22].

The efficiency frontier is constructed by plotting all

elevant interventions within one indication on a plane,epicting costs on the horizontal and health effects on theertical axes. All interventions that are not subject to simpler extended dominance are connected in ascending order of

economic evaluation

nsurants. In addition, analyses from other perspectives mayches of social security such as statutory long-term care

ned by Federal Joint Committee.al as well as non-pharmaceutical) within an pre-specified

ncy frontier approach. Single or several endpointsgated outcomes may be applied—–if appropriate. Ae costing and modelling.t caveat against life-long time horizon.e), but also indirect or unrelated future costs depending on

ainst the use of QALYs is issued.input parameters, assumptions etc. and publication of an

ier.se for costs and effects and of 0 to 5% in sensitivity analyses.alyses.

eters (except for health effects). Detailed documentation of

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effectiveness. The resulting curve consists solely of efficientinterventions. For a new intervention under assessment, areimbursable price must be set such that the associatedcosts and effect(s) lie on (the linearly extrapolated lastsegment of) the efficiency frontier. The line extrapolatedbeyond the last segment of an efficiency frontier uses thesame trade-off rate for costs and health effects as for thecurrent most effective intervention relative to the secondmost effective intervention. Hence, an increase in effec-tiveness is valued by using an observed indication-specifictrade-off between costs and effects [14,23].

Given the aim of a health economic evaluation in theGerman SHI system, cost-effectiveness analyses which com-pare interventions within an indication are the preferredstudy type. A cost-utility-analysis can particularly be use-ful when comparing within a therapeutic area and when noother validated tool to aggregate the assessment of benefitand harm is available. Given the indication-specific analy-sis in the German setting, quality-adjusted life years areneither a required nor a favored endpoint. The methods ofIQWiG further demand and include the perspective of SHIinsurees in the base case analysis (thus including disease-related benefits covered by SHI as well as co-payments);further perspectives could be included if deemed appropri-ate [14].

Assessing uncertainty is a salient issue in every healtheconomic evaluation and international good practices existto which IQWiG refers in its updated methods [24]. Alongwith deterministic and probabilistic sensitivity analyses,scenario analyses are required. In the case of IQWiG’sefficiency frontier approach, two sources of additionaluncertainty arise. The first stems from the use of a mixed-treatment comparison analysis. This technique, roughlyspeaking, allows comparison of the clinical effectiveness ofdifferent interventions even if no head-to-head-trials exist.As the efficiency frontier approach implies to cover thewhole indication area and a range of treatments, whereasrandomized controlled trials have frequently only been con-ducted against placebo, this is often necessary.

The second source of uncertainty stems from displayingthe efficiency frontier itself. In each run of a probabilis-tic sensitivity analysis the position of an intervention onthe cost-effectiveness plane varies. This of course means,that in each run, the shape of the efficiency frontier—–to which the intervention is compared—–varies as well. Tothis purpose, IQWiG—–together with a group of internationalexperts—–adapted an already existing measure to visual-ize the uncertainty, namely the net monetary benefit [23].The net monetary benefit quantifies the positive or nega-tive monetary benefit that an intervention yields, given itscost and benefit, as compared to a given willingness-to-paythreshold. In each run of the probabilistic sensitivity anal-ysis, the incremental net monetary benefit is calculated bymeasuring the distance between the intervention and the(last segment of the) efficiency frontier.

Current legal situation: Process of health

economic evaluation according to AMNOG

As stated in the current version of the Social Code BookV, there are two ways in which the FJC may commission

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supporting tool a sleeping beauty? 393

health economic evaluation: In §139a SGB V, the FJCay charge IQWiG with the health economic evaluation in

ombination with a full benefit assessment of any kind ofntervention. In §35b SGB V, health economic evaluationsf new drugs being evaluated in the early benefit assess-ent according to AMNOG are stipulated. Given the focus

n health economic evaluations of drugs in Germany—–andhe lack of such requirements and regulations for non-drugnterventions as established with AMNOG—–we will describehe process according to AMNOG next.

In essence, AMNOG requires manufacturers of drugs withew active ingredients entering the German market torovide a dossier on the patient-relevant added benefit inomparison with an appropriate comparator therapy (initi-ting the early benefit assessment). Note: the dossier doesot contain a health economic evaluation at this stage. Theossier includes a systematic review of all published andnpublished clinical trials as well as estimates for the annualumber of patients potentially benefitting from the newrug and the forecasted annual drug costs [25]. The FJChen commissions IQWiG with the assessment of the dossierithin a 3 month period. After the assessment by IQWiGnd within another 3 months, the FJC then decides on therug’s added benefit: if an equivalent benefit is proven forifferent agents in a class of drugs, e.g. statins or protonump inhibitors, reference pricing does not allow a highereimbursement for patent over off-patent generic formu-ae. In case of an added benefit, the economic informations the basis for price negotiations between the manufacturernd the National Association of Statutory Health Insuranceunds (= GKV-Spitzenverband, the SHI-funds umbrella orga-ization). If no agreement is reached within the followingeriod of 6 months, an arbitration process is started (theime frame for this is again 3 months) [6].

In the case of the FJC concluding that a new interven-ion had ,,no added benefit‘‘ or there being no therapeuticmprovement (6 months after initiating the early benefitssessment; see §35a sec. 5a SGB V), the manufacturer canle an application for a health economic evaluation with theJC. Furthermore, both the manufacturer and the SHI-fundsmbrella organization can apply for a health economic eval-ation after the ruling of the arbitration board (15 monthsfter initiating the early benefit assessment; see §130b sec.SGB V). Thus, next to the two stated (diverging) pricing

deas of payer and manufacturer and one internationallyeferenced price of the arbitration board, a health economicvaluation with the efficiency frontier approach can thenrovide a fourth, evidence-based reimbursement price.

After the application for a health economic evaluationas been accepted by the FJC, a scoping workshop is heldnd distinctive elements of the assessment are defined,ncluding: the comparators (which are not limited to drugs),atient (sub-)groups, the perspective (it should regularly behe SHI insurees’ perspective), the time horizon, the kind ofenefits and costs to consider, the overall measure of benefitsee §35b SGB V and FJC’s rules of procedure [26]). The FJChen i) requests the manufacturer to supply a dossier con-aining the health economic evaluation within 3 months and

i) concurrently commissions IQWiG with the assessment ofhe dossier. The manufacturer is required to conform to theJC dossier template for health economic evaluation [27],hich is based on IQWiG’s methods and is an integral part

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f the rules of procedure (= Verfahrensordnung) of FJC [26].linical studies and studies of real-world data (which can belanned prospectively by the manufacturer and may extendhe submission date of a dossier by a maximum of 3 years)rovide the basis of the health economic evaluation.

If the dossier received by IQWiG is not complete, IQWiGtself will undertake a full health economic evaluation. Nei-her the FJC nor IQWiG have the obligation to consider aelayed dossier (or delayed additional information). A pre-iminary assessment by IQWiG is done within 12 months,fter a formal hearing, the final assessment is sent to theJC within another 3 months. Further procedural detailsor a health economic evaluation of drugs are also spec-fied in the rules of procedure [26]. Of note: within theMNOG-framework, the law currently stipulates that only

QWiG may be charged with the conduct of (or assessmentf dossiers containing) health economic evaluations for theecision-making process of the FJC.

Different stakeholders are involved at several pointshroughout the process of a health economic evaluation.irst and foremost, the FJC consists of patient repre-entatives who participate in the scoping workshop of aealth economic evaluation. Secondly, industry represent-tives may also submit their oral or written opinion. AtQWiG, patient representatives and clinical experts are usu-lly involved in the assessment of the patient relevancef the clinical evidence. Before the final report is pub-ished, IQWiG distributes a preliminary report and invitesll interested parties to a formal hearing. Finally, duringhe decision process at the FJC, industry representativesay once more present additional evidence and voice their

bjections regarding the final report.

mpact of health economic evaluations usingQWiG’s methods on the currentecision-making process in Germany

fter the development of IQWiG’s health economic evalu-tion methods, including the efficiency frontier approach,QWiG was commissioned with two reports by FJC in late009.1 The basis was a full benefit assessment that IQWiGad performed in the previous years, demonstrating addedenefit of some antidepressants and clopidogrel. WhileQWiG was working on the health economic evaluations ofntidepressants and of clopidogrel for the prevention ofyocardial infarction, the enactment of AMNOG within 13onth after these commissions had been assigned made it

nclear whether the FJC would be able to use the healthconomic evaluations for their decision-making process.evertheless, IQWiG finalized the report on antidepressantsith the efficiency frontier approach in September 2013

28,29] while the second commission was withdrawn by theJC in agreement with IQWiG in October of 2012 [30]. The

nal report on antidepressants has not been used by the FJC.s of June 2014, no health economic evaluation has beenommissioned according to §35b. Likewise, no other health

1 Three pilots on the efficiency frontier that had been commis-ioned by IQWiG to three groups of external experts had beenresented orally on June 30th, 2009 at a meeting in Berlin.

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A. Gerber-Grote et al.

conomic evaluation for any drug or non-drug interventionccording to §139a has been commissioned ever since theegal requirements were established (i.e., 2007 and 2004)r the methods were specified (in 2009). Overall, the cur-ent impact (as of mid-2014) of health economic evaluationsor statutory decision making in Germany has been factuallyon-existent (see also [31,32]).

At the moment and to the best of our knowledge, onlyne independent scientific peer-reviewed article for theerman context exists which applies the efficiency frontiers it was suggested in IQWiG’s health economic evalua-ion methods (though modified to a ‘‘shortcut’’-application)33].

hy does the health economic evaluation notave a more prominent role in the Germanystem?

e initially attempted to answer this question but foundhat it may be a rather speculative endeavor, as variousuthors have come up with divergent explanations whyealth economic evaluation has the position it holds [9].s mentioned above, interpretations range from histori-al approaches which argue that the reluctance to adoptealth economic evaluation may be founded in the timef the Nazi regime [8] to more sociological approaches.he latter approach is based on the analysis of powerf institutions and tries to explain that neither the SHI-unds umbrella organization nor the manufacturers maye willing to forfeit their power of price negotiation.n the other hand, all stakeholders seem to feel com-

ortable with the results of the negotiations, particularlyith regard to the current financial situation of the SHI-

unds.Furthermore, some experts argue that a debate on the

elevance of health economic evaluation has not yet takenlace in the German public (and not all parties involveday be aware of the possibilities and limitations of a

ealth economic evaluation). Others, in daily encounters,learly experience that the public is aware of the facthat very expensive drugs, particularly in oncology, mayot be worth their price given their (limited) added ben-fit.

Also, evidence-based medicine is an established methodn Germany, which, when applied in comparative effective-ess research, may lead to easily comprehensible resultsven for laypersons. The efficiency frontier and its pro-ortional decision rule [34] are likewise easy to grasp; yethe method has been discussed controversially and was par-icularly at the time of its origin not endorsed, includingy the German health economists associations [22]. Somergue that this debate and controversy among scientists alsoed to the confusion of whether or not to use health eco-omic evaluations [32]. Yet, while many objections equallyold true for the conventional fixed-threshold approachn health economic evaluation (among which the time itould take to perform a health economic evaluation of

ultiple interventions as well as the transparency), the

dvantages of the efficiency frontier method and possibil-ties for shortening the assessment process remain mostlynnoticed [9,15,34—36]. In a climate of political fear of

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Decision making in Germany: Is health economic evaluation

rationing and prioritization in the health care system itmight be a simple strategy of avoidance on behalf of thegovernment and the ministry of health, thereby evading thediscussion on costs (and economic evaluation) related tohealth.

Even if AMNOG was introduced with the aim of a costconstraint in the market of patented drugs, the financialsituation of the SHI funds has been exceptionally comfort-able in the last few years. The system therefore did notface much pressure to achieve the best value for money.This may also be reflected by the fact that while very spe-cific legal and procedural requirements were laid out forthe health economic evaluation of drugs (last with AMNOG),the same does not apply to non-drug interventions althoughdesirable from our point of view. It thus remains an openquestion how long the value of health economic informationcan be withheld from the German SHI system before thissleeping beauty is awakened from its long-lasting sleep—–wehope it will not take 100 years as in the fairytale by the samename.

Conflict of interest

All authors have no conflict of interest to declare.

Acknowledgement

The authors would like to thank Consuela Jacobi-Yniguez forthe English editing.

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