Pharmaceuticals In Germany Research Articles

10 Years of AMNOG: What is the Willingness-to-Pay for Pharmaceuticals in Germany?

The German Pharmaceutical Market Restructuring Act (AMNOG, 2011) is a two-stage process to regulate the price of new pharmaceuticals in which price negotiations are conducted based on evidence-based medical benefit assessments using data from prior clinical trials. Although the act does not explicitly set a willingness-to-pay (WTP) threshold, the process itself implicitly establishes a WTP for health improvement. We evaluated the implicit WTP for prescription pharmaceuticals post-AMNOG in the German healthcare system from the decision-maker/payer perspective. We extracted data on patient-group-specific annual treatment costs and endpoints from 2011 to 2021 from the dossiers assessed by the German Federal Joint Committee (FJC; Gemeinsamer Bundesausschuss). Using incremental cost-effectiveness ratios (ICERs), we calculated a WTP for the indications (I) diabetes, (II) cardiovascular disease, and (III) psoriasis weighted according to patient group size, first from the perspective of the decision-maker (approach A), and second from the perspective of the industry (approach B). To put clinical outcome measures into relation to one another, minimum clinically important differences (MCIDs) were derived from the literature and compared. The annual treatment costs of newly authorized drugs were substantially higher (both pre- and post-negotiation) than that of their comparators (e.g., psoriasis, pre-negotiation: €20,601.59, post-negotiation: €16,763.57; comparators: €5178.00). However, although newly launched drugs were more expensive than their comparators, they brought greater medical benefits and were more aligned with value (r = 0.59, P < 0.001) than older drugs. We estimated WTP to vary widely by indication group [€33,814.08 per 1 percentage point hemoglobin A1c (HbA1c) reduction for diabetes, €10,970.83 per life year gained for cardiovascular disease, and €663.46 per 1% PASI decrease for psoriasis; approach A]. WTP was converted to MCID thresholds: diabetes: €16,907.04; cardiovascular drugs: no MCID existent to convert; and psoriasis: €33,173.00. WTP remained constant over time for diabetes and cardiovascular drugs but increased for psoriasis drugs. This paper is one of the first to estimate the implicit WTP for prescription pharmaceuticals post-AMNOG and suggests that the WTP may vary between different therapeutic areas. Additionally, making different assumptions (approach A versus approach B) with regard to the assumed effectiveness in indication areas that had been declared as having no additional benefit by the FJC may explain the different perspectives of decision-makers and of the pharmaceutical industry on the value of a pharmaceutical.

Does health technology assessment compromise access to pharmaceuticals?

In response to rapidly rising pharmaceutical costs, many countries have introduced health technology assessment (HTA) as a ‘fourth hurdle’. We evaluated the causal effect of HTA based regulation on access to pharmaceuticals by using the introduction of Germany’s HTA system (AMNOG) in 2011. We obtained launch data on pharmaceuticals for 30 European countries from the IQVIA (formerly IMS) database. Using difference-in-difference models, we estimated the effect of AMNOG on launch delay, the ranking order of launch delays, and the availability of pharmaceuticals. We then compared the results for Germany to Austria, Czechia, Italy, Portugal, and the UK. Across all six countries, launch delays decreased from the pre-AMNOG period (25.01 months) to the post-AMNOG period (14.34 months). However, the introduction of AMNOG consistently reduced the magnitude of the decrease in launch delay in Germany compared to the comparator countries (staggered DiD: + 4.31 months, p = 0.05). Our logit results indicate that the availability of pharmaceuticals in Germany increased as a result of AMNOG (staggered logit: + 5.78%, p = 0.009). We provide evidence on the trade-off between regulation and access. This can help policymakers make better-informed decisions to strike the right balance between cost savings achieved through HTA based regulation and access to pharmaceuticals.

POSC253 Analysis of Result of Early Benefit Assessment and Reimbursement Price After Free-Pricing Period in Germany

The outcome of the early benefit assessment process (according to §35a SGB V) is crucial for the successful launch and commercialization of pharmaceuticals in Germany. We aim to analyze the change in reimbursement price after early benefit assessment for the first non-orphan evaluation of a drug.

Modeling the use and end-of-life phase of pharmaceuticals in support of a life cycle inventory analysis – Case study on different antibiotics in Germany

More focused measurements on antibiotics in the environment enable a more accurate assessment of potential risks to human health and ecosystems. Therefore, antibiotics are ranked as highly relevant with efforts to monitor and systematically map them (e.g., German Antibiotic Resistance Strategy, European Antimicrobial Resistance Surveillance Network, Global Antimicrobial Resistance Surveillance System). Due to limited life cycle analysis data, a recently developed life cycle inventory model to assess the use and end-of-life phase of pharmaceuticals in Germany is applied and reviewed for antibiotics, representatively for amoxicillin, ciprofloxacin and clarithromycin. Necessary data are collected from experimental research, publications by official agencies and data fact sheets by pharmaceutical companies, among others. To evaluate the model's accuracy and prediction potential, the results are compared to literature findings. The model predicts the emission pathway via the sewage treatment effluent to be the primary route ranging from 39.5% (clarithromycin) to 67% (amoxicillin). Accumulation in the sewage sludge is relevant for ciprofloxacin (24.3%) whereas clarithromycin shows the highest biodegradability (15.8%). Gaseous emissions are not predicted. Modeling of metabolites is not reliable because of major data gaps regarding the chemical structure and coherent physicochemical properties. The results highlight that currently neglected transformation processes (especially hydrolysis) need to be implemented prospectively to reclassify the gained results. Investigation of other software than SimpleTreat 4.0 should be done to display the fate of substances in sewage treatment plants more precisely. Also, more experimental, and scientifically assured data are needed to confirm the ratio of the antibiotics' pathways.

Research of Natural Health Products is Lacking – Right?

In May 1994, while working in marketing for BASF Pharmaceuticals in Germany, I was prescribed a product called Sinupret® for chronic sinusitis by my family physician. The product was behind the counter in the local pharmacy and was reimbursed by my health insurance. After some months, my sinusitis was gone and I was intrigued about the product, its regulation and most particularly the research behind it. In reading the Sinupret® packet I discovered to my surprise that it was a herbal medicine. Convinced, with my pharma background, that there would be little evidence for such a product I asked our medical information department to conduct a literature review of all clinical trials for herbal medicines in all languages. A week later I received 4 thick lever arch files of abstracts of tens of thousands of clinical trials on hundreds of products. This delivery changed my life!

PMU39 Determinants of Willingness to Copay for Pharmaceuticals in Germany

Focussing on German subjects, this study tries to assess people’s willingness to co-pay for pharmaceuticals and potential determinants influencing their decision. While pricing decisions are usually made by political institutions on behalf of the population, the aim of this study is to shed some light on the actual preferences of the latter in order to potentially allow institutions to make better informed decisions. A survey was conducted to elicit information about people’s willingness to co-pay. Twelve different treatments were applied, differing in described disease and stated reference price. A total of 1,199 people participated in the survey. The analyses show the co-payment to be strongly affected by the participant’s perception of the pharmaceutical’s benefit. Moreover, the perception of the pharmaceutical’s benefit is positively affected by the participants’ confidence in the German (healthcare) system and its social security. Also, the stated co-payment is higher if participants (a) are covered by private health insurance, (b) state a higher willingness to consume, (c) have more conservative values, and (d) express social security to be less important. Furthermore, participants who received information on the price of the pharmaceutical (2/3 of the cases) are willing to co-pay a higher amount of money. While the data show the valuation for pharmaceuticals in Germany to positively correlate with their benefit, it also highlights a significant amount of heterogeneity in the queried subjects. From a policy point of view, we take the latter result as emphasising the fact that the value of health care requires a social debate - possibly differentiating between the groups targeted with a certain measure.

PNS205 SURROGATE VALIDATION IN GERMAN AMNOG BENEFIT ASSESSMENTS

In clinical trials surrogate endpoints are oftentimes used as substitute for patient-relevant endpoints. However, in the early benefit assessment of pharmaceuticals in Germany and in order be able to provide patient-relevant evidence a validation of surrogate endpoints is critical. The aim of this study was to assess the utilization, methodology and acceptance of surrogate validations in AMNOG benefit dossiers. Dossiers for benefit assessment were retrieved from the homepage of the Federal Joint Committee (G-BA). It was assessed whether the pharmaceutical companies performed a surrogate validation and if a surrogate parameter was considered for benefit assessment by the Institute for Quality and Efficiency in Health Care (IQWiG) and later accepted by the G-BA. In total 397 AMNOG dossiers were analyzed. In 105 (26.4%) dossiers a surrogate validation was presented. Of all attempted surrogate validations, 36 (34.3%) were rejected and 51 (48.6%) were not further commented (e. g. due to limitations in study design). In total, 18 validations (17.1% of all attempted validations) were accepted as valid. Validations were only accepted in infectious indications (94.4%) and oncological diseases (5.6%). Accepted endpoints were (sustained) virologic response for reduced risk for hepatocellular carcinoma as well as AIDS-defining diseases/death, CD4 cell count for AIDS-defining diseases/death and disease-free survival (DFS) for overall survival. In most cases the pharmaceutical companies referred to prior benefit assessments. Only for DFS a comprehensive surrogate validation including systematic literature search and statistical calculations was performed. Even though the methodological demands by IQWiG are high, in one quarter of submitted dossiers pharmaceutical companies attempted to validate a surrogate parameter as a patient-relevant endpoint. Overall, the acceptance of validations is possible; however, the success rate is small (17%). Most accepted surrogate validations were within infectious diseases and their validation referred to prior benefit assessments.

PCN386 GERMAN BENEFIT ASSESSMENT IN THE FIELD OF ONCOLOGY: FACTORS INFLUENCING THE BENEFIT RATING IN ADDITION TO COMPLYING WITH THE APPROPRIATE COMPARATOR

For benefit assessment of new pharmaceuticals in Germany, the Federal Joint Committee (FJC) defines appropriate comparators of four categories: one specific drug, a list of drugs, patient individualized therapy, and best supportive care (BSC). The aim of the study was to evaluate factors influencing the outcome of the assessments in oncological indications with a negative benefit rating in addition to complying with the assigned appropriate comparator. Information on appropriate comparators and benefit assessment were retrieved from a databank containing information on all AMNOG dossiers in the field of oncology. Dossiers were analyzed for data on indication, target population, line of therapy, appropriate comparator, and added Benefit. 109 dossiers including 215 separate (sub) labels were identified in the field of oncology between 2011 and 2018. The appropriate comparators assigned by FJC were distributed as follows: 51 (24%) specific drug, 88 (40%) list of drugs, 35 (17%) patient individualized therapy, and 41 (20%) BSC. More than half of these benefit assessments resulted in no added benefit despite compliance with the FJC-assigned comparator in the dossier. Factors leading to a negative benefit rating in these assessments were identified by analyzing the reasons for the FJC decision. Four major reasons for negative benefit ratings can be determined: low quality of evidence, lack of patient relevant study endpoints, discrepancy between label and study population and insufficient study design. The appropriate comparator assigned by FJC significantly influences the outcome of AMNOG benefit assessment. Even if a comparison against the appropriate comparator is performed in the AMNOG dossier, further factors play an important role for a positive outcome of the assessment, comprising the quality of evidence, the patient relevance of study endpoints, the alignment between study and label population as well as and the quality and validity of the study.

PP84 Different Interpretation Of Evidence By A Health Technology Assessment Body And A Decision Maker

IntroductionWithin early benefit assessment of pharmaceuticals in Germany, addenda can be commissioned by the Federal Joint Committee (FJC) to the health technology assessment (HTA) agency, mainly as a result of a hearing. Our aim was to analyze the issues for and impact of commissioned addenda, as well as the agreement between HTA agency recommendations and FJC decisions.MethodsAll available relevant documents on addenda commissioned up to the end of 2017 were screened and their essential content extracted. Differences between the HTA agency and FJC recommendations were tested, and concordance was analyzed using agreement statistics (Cohen's kappa and Fleiss’ kappa).ResultsMost of the 90 addenda commissioned up to the end of 2017 concerned oncological products. In all contingent comparisons, positive changes in added benefit or evidence level on a subpopulation basis (n = 124) were more common than negative changes. Agreement of assessments, addenda, and appraisals reached a moderate strength for added benefit (Fleiss’ kappa 0.47, range 0.41 - 0.54). Overall agreement between addenda and appraisals on a binary nominal basis was poor for added benefit (Cohen's kappa 0.18, range 0.01 - 0.36) and fair for evidence quality (Cohen's kappa 0.35, 0.19–0.52). Cohen's kappa ranged from “less than by chance” (respiratory diseases) to “perfect” (neurological diseases), but was only statistically significant for neurological and other diseases. Three addenda are presented in detail as examples.ConclusionsAddenda have a high impact on decision-makers’ appraisals, offering additional analyses of supplementary evidence submitted by the manufacturers. Nevertheless, the agreement between addenda and appraisals varies, highlighting different methodological approaches and decision-making factors between the HTA agency and the FJC.

Product liability for medicinal pharmaceuticals in Germany

Product liability for medicinal pharmaceuticals in Germany

Retracted: Combined therapy using LHRH-PE40 and anti-CD40 dendritic cells substantially eliminate tumor cells.

LHRH-PE40 was used to promote the proliferation of bone marrow derived cell (BMDC) and improve the antigen-presenting ability of BMDC as well as the immune function via the CD40 signal pathway. LHRH-PE40 was also implicated in cancer treatment, targeting a variety of cancer cells that express luteinizing hormone-releasing hormonereceptor (LHRHR). In the present study, the mechanism and efficacy of LHRH-PE40 were addressed in the following three aspects. Enzyme-linked immunosorbent assay was performed to confirm the binding specificity of LHRH-PE40 to LHRHR. The killing effect of LHRH-PE40 on target cells was mediated by LHRHR, which specifically killed LHRHR-positive target cells while the minimal cytotoxicity of LHRHR-negative cells is negligible. Spiegelmers, a molecule mutually exclusive with GnRH and developed by Sven Klussmann and Dr Sven Klussmann of NOXXON Pharmaceuticals in Germany, demonstrated that LHRH-PE40 maintains a combinatory characteristics of LHRH and LHRHR. In the end, the mechanism of LHRH-PE40 underlying induction of apoptosis at low concentration and prolonged conditions was firstly demonstrated by the basic method of detecting apoptosis to induce apoptosis. It provided a scientific basis for clinical application of LHRH-PE40 and laid a foundation for the further study of LHRH-PE40 on inducing apoptosis of target cells. The target cells herein refer to tumor cells that overexpress LHRHR. This study shows that activated DC can more effectively promote the proliferation of CD4+ T cells, and initially proved that DC carrying anti-CD40 antibody promoted the immune treatment of the tumor. Combining LHRH-PE40 with anti-CD40 DCs achieved substantially improved efficacy in killing tumor cells.

Methodological problems in the method used by IQWiG within early benefit assessment of new pharmaceuticals in Germany.

The decision matrix applied by the Institute for Quality and Efficiency in Health Care (IQWiG) for the quantification of added benefit within the early benefit assessment of new pharmaceuticals in Germany with its nine fields is quite complex and could be simplified. Furthermore, the method used by IQWiG is subject to manifold criticism: (1) it is implicitly weighting endpoints differently in its assessments favoring overall survival and, thereby, drug interventions in fatal diseases, (2) it is assuming that two pivotal trials are available when assessing the dossiers submitted by the pharmaceutical manufacturers, leading to far-reaching implications with respect to the quantification of added benefit, and, (3) it is basing the evaluation primarily on dichotomous endpoints and consequently leading to an information loss of usable evidence. To investigate if criticism is justified and to propose methodological adaptations. Analysis of the available dossiers up to the end of 2016 using statistical tests and multinomial logistic regression and simulations. It was shown that due to power losses, the method does not ensure that results are statistically valid and outcomes of the early benefit assessment may be compromised, though evidence on favoring overall survival remains unclear. Modifications, however, of the IQWiG method are possible to address the identified problems. By converging with the approach of approval authorities for confirmatory endpoints, the decision matrix could be simplified and the analysis method could be improved, to put the results on a more valid statistical basis.

Confirmatory versus explorative endpoint analysis: Decision-making on the basis of evidence available from market authorization and early benefit assessment for oncology drugs

The early benefit assessment of pharmaceuticals in Germany and their preceding market authorization pursue different objectives. This is reflected by the inclusion of varying confirmatory endpoints within the evaluation of oncology drugs in early benefit assessment versus market authorization, with both relying on the same evidence. Data from assessments up to July 2015 are used to estimate the impact of explorative in comparison to confirmatory endpoints on market authorization and early benefit assessment by contrasting the benefit-risk ratio of EMA and the benefit-harm balance of the HTA jurisdiction. Agreement between market authorization and early benefit assessment is examined by Cohen’s kappa (k). 21 of 41 assessments were considered in the analysis. Market authorization is more confirmatory than early benefit assessment because it includes a higher proportion of primary endpoints. The latter implies a primary endpoint to be relevant for the benefit-harm balance in only 67% of cases (0.078). Explorative mortality endpoints reached the highest agreement regarding the mutual consideration for the risk-benefit ratio and the benefit-harm balance (0.000). For explorative morbidity endpoints (−0.600), quality of life (−0.600) and side effects (−0.949) no agreement is ascertainable. To warrant a broader confirmatory basis for decisions supported by HTA, closer inter-institutional cooperation of approval authorities and HTA jurisdictions by means of reliable joint advice for manufacturers regarding endpoint definition would be favorable.

Quality Assured Use of Pharmaceuticals: Does German Gba Follow Ema?

After receiving the EMA approval for Europe, it is mandatory for pharmaceuticals in Germany to complete the AMNOG process to receive reimbursement. Finally the responsible G-BA (joint federal committee) publishes a decision not only on the added benefit of the drug, but also on any specific requirements for the quality assured use. These requirements may differ from the EPAR and SmPC specifications for quality assured use of the drug. For all 110 AMNOG applications started and finished between January 2015 and June 2017 we compared the specifications of the AMNOG decision for quality assured use with the respective EPAR and SmPC documents. We categorized differences and determined its relative amounts. The G-BA decisions were clustered into three groups: [A] Complete agreement with the EPAR/SmPC documents (52%), [B] Concretization of the EPAR/SmPC requirements (41%) and [C] divergent requirements by G-BA (7%). In cases of category [B] the G-BA named the type of specialized physicians indicated by the EMA phrasing “…a physician experienced with…”. All products of category [C] receiving divergent specifications (7%, n=8) were orphan drugs and two of them had an oncologic indication while the others were for metabolic diseases. While EPAR and SmPC mentioned "health care professionals" or had no specific assignation, the G-BA assigned the application of the drug to specific disciplines. The G-BA gives no explicit reasons for this decision, but the orphan drug status appears to be an important driver. In case of rare diseases German Health authorities request supervision by a specialized and experienced physician, also in cases where the EMA does not. This should be taken into concern when the market entry of an orphan drug is projected, especially for critical indications like cancer or severe neurologic and metabolic diseases.

German Amnog Benefit Assessment: The Type Of Appropriate Comparator Makes The Difference

For benefit assessment of new pharmaceuticals in Germany, G-BA defines appropriate comparators of four categories: one specific drug, a list of drugs, patient individualized therapy, and best supportive care (BSC). The aim of the study was to reveal the impact of the category on the added benefit. Information on appropriate comparators and benefit assessment were retrieved from a databank containing information on all AMNOG dossiers in the field of oncology. Dossiers were analyzed for data on indication, target population, line of therapy, appropriate comparator, and added benefit. 66 relevant dossiers including 129 separate (sub-)labels were identified. Appropriate comparators assigned by G-BA were distributed as follows: 33 (26%) specific drug, 39 (30%) list of drugs, 23 (18%) patient individualized therapy, and 34 (26%) BSC. About 50% of all assessed sublabels within the categories “specific drug” and “list of drugs” gained an added benefit (45.5% and 46.2%, respectively). In nearly all of these dossiers direct evidence to the assigned comparator was presented. 41.2% (n=14) of the indications in the category “BSC” gained an added benefit. In 3 dossiers no direct evidence to the appropriate comparator was presented. Nevertheless, 2 of these dossiers achieved an added benefit. In contrast, an added benefit was granted for only 30.4% (n=7) of sublabels, which belonged to the category “patient individualized care”, 9 of the dossiers in this category did not show direct evidence to the appropriate comparator; however, 3 of these dossiers achieved an added benefit. A specific drug or BSC are the most commonly assigned appropriate comparators in oncology dossiers. If a specific drug is the appropriate comparator, it seems inevitable to present direct evidence in order to gain an added benefit. For BSC and patient individualized therapy, G-BA seems to be more permissive regarding the acceptance of evidence not directly matching the appropriate comparator.

Intellectual property rights on pharmaceuticals in Germany—a moral evaluation

Diese Arbeit untersucht die Frage, ob der aktuelle Schutz des geistigen Eigentums bei Arzneimitteln in Deutschland moralisch zu rechtfertigen ist. Die Untersuchung orientiert sich dabei am aktuellen Diskurs und ordnet die bestehenden Positionen entsprechend ihrer Abstraktheit. Dabei bilden Argumente gegen einen Schutz geistigen Eigentums die allgemeinste Ebene, und Argumente, die sich spezifisch gegen deutsche Arzneimittelpatente richten, die konkreteste Ebene. Ich werde zeigen, dass starke deontologische und konsequentialistische Positionen existieren, welche die realpolitischen Auswirkungen von Arzneimittelpatenten kritisieren. Die konsequentialistische Position argumentiert in erster Linie mit den jungsten Wirtschaftsdaten, wahrend die deontologische Position die burgerlichen Autonomieanspruche betont.

Imaginary Worlds and Efficiency Frontiers: Should We Abandon the IQWiG Health Technology Assessment Model?

The contribution of cost-effectiveness analysis to the pricing of pharmaceuticals in Germany is at best marginal and in many, if not most cases, absent. While this may reflect a reasonable belief that cost-effectiveness analysis adds little if anything to pricing and formulary placement decisions, its marginalization reflects considerable dissatisfaction, if not frustration, with modeling efforts by the Institut für Qualität und Wirtschaftlichkeit im Gesundheitseesen (IQWiG). In part, this reflects the rejection of quality adjusted life years (QALYs) as the common outcome standard, together with the adoption of the efficiency frontier as the default framework for modeled claims. The purpose of this commentary is to consider the merits, in the German context, of an efficiency frontier framework for cost-effectiveness and pricing decisions. The commentary concludes that the efficiency frontier framework for health technology assessment, in supporting the creation of non-evaluable claims from models or simulations, fails of to meet the standards of normal science: it fails to support claims that are credible, evaluable and replicable. It should be abandoned. If cost-effectiveness modeling is to play a constructive role in pricing negotiations in Germany then manufacturers should be required to submit evaluable claims. The most effective way of ensuring this is to require manufacturers to accompany any submission for a new product with a protocol detailing how their claims, to include those for clinical outcomes, cost-effectiveness and budget impact, are to be evaluated and reported to decision makers in a meaningful time frame.&#x0D; &#x0D; Type: Commentary

Imaginary Worlds and Efficiency Frontiers: Should We Abandon the IQWiG Health Technology Assessment Model?

The contribution of cost-effectiveness analysis to the pricing of pharmaceuticals in Germany is at best marginal and in many, if not most cases, absent. While this may reflect a reasonable belief that cost-effectiveness analysis adds little if anything to pricing and formulary placement decisions, its marginalization reflects considerable dissatisfaction, if not frustration, with modeling efforts by the Institut fur Qualitat und Wirtschaftlichkeit im Gesundheitseesen (IQWiG). In part, this reflects the rejection of quality adjusted life years (QALYs) as the common outcome standard, together with the adoption of the efficiency frontier as the default framework for modeled claims. The purpose of this commentary is to consider the merits, in the German context, of an efficiency frontier framework for cost-effectiveness and pricing decisions. The commentary concludes that the efficiency frontier framework for health technology assessment, in supporting the creation of non-evaluable claims from models or simulations, fails of to meet the standards of normal science: it fails to support claims that are credible, evaluable and replicable. It should be abandoned. If cost-effectiveness modeling is to play a constructive role in pricing negotiations in Germany then manufacturers should be required to submit evaluable claims. The most effective way of ensuring this is to require manufacturers to accompany any submission for a new product with a protocol detailing how their claims, to include those for clinical outcomes, cost-effectiveness and budget impact, are to be evaluated and reported to decision makers in a meaningful time frame. Type: Commentary

PHP216 - Participation Of External Medical Societies In The Benefit Assessment Of Pharmaceuticals In Germany

PHP216 - Participation Of External Medical Societies In The Benefit Assessment Of Pharmaceuticals In Germany

Oxypurinol – A novel marker for wastewater contamination of the aquatic environment

The anti-gout agent allopurinol is one of the most prescribed pharmaceuticals in Germany and is widely metabolized into oxypurinol (80%) as well as the corresponding riboside conjugates (10%) within the human body. To investigate the occurrence of allopurinol and oxypurinol in the urban water cycle an analytical method was developed based on solid phase extraction (SPE) and subsequent liquid chromatography electrospray-ionization tandem mass spectrometry (LC-MS/MS).In raw wastewater concentration levels of oxypurinol ranged up to 26.6 μg L−1, whereas allopurinol was not detected at all. In wastewater treatment plant (WWTP) effluents, concentrations of allopurinol were <LOQ, whereas oxypurinol concentrations ranged from 2.3 μg L−1 to 21.7 μg L−1. Elevated concentrations of oxypurinol in biologically treated wastewater originate from the transformation of allopurinol as well as the cleavage of allopurinol-9-riboside, which was confirmed by laboratory experiments with activated sludge taken from a municipal WWTP.Further tracking of oxypurinol in the urban water cycle revealed its presence in rivers and streams (up to 22.6 μg L−1), groundwater (up to 0.38 μg L−1) as well as in finished drinking water (up to 0.30 μg L−1). Due to the high biological stability and the almost ubiquitous presence in the urban water cycle at elevated concentrations, oxypurinol might be used as marker for domestic wastewater in the environment. This was confirmed by correlation analysis to other wastewater markers with strong correlations of the concentrations of oxypurinol and carbamazepine (r2 = 0.89) as well as of oxypurinol and primidone (r2 = 0.82).