Michelle Maria Aleida Kip

A PCT algorithm for discontinuation of antibiotic therapy is a cost-effective way to reduce antibiotic exposure in adult intensive care patients with sepsis

Abstract Objective: Procalcitonin (PCT) is a specific marker for differentiating bacterial from non-infective causes of inflammation. It can be used to guide initiation and duration of antibiotic therapy in intensive care unit (ICU) patients with suspected sepsis, and might reduce the duration of hospital stay. Limiting antibiotic treatment duration is highly important because antibiotic over-use may cause patient harm, prolonged hospital stay, and resistance development. Several systematic reviews show that a PCT algorithm for antibiotic discontinuation is safe, but upfront investment required for PCT remains an important barrier against implementation. The current study investigates to what extent this PCT algorithm is a cost-effective use of scarce healthcare resources in ICU patients with sepsis compared to current practice. Methods: A decision tree was developed to estimate the health economic consequences of the PCT algorithm for antibiotic discontinuation from a Dutch hospital perspective. Input data were obtained from a systematic literature review. When necessary, additional information was gathered from open interviews with clinical chemists and intensivists. The primary effectiveness measure is defined as the number of antibiotic days, and cost-effectiveness is expressed as incremental costs per antibiotic day avoided. Results: The PCT algorithm for antibiotic discontinuation is expected to reduce hospital spending by circa €3503 per patient, indicating savings of 9.2%. Savings are mainly due to reductions in length of hospital stay, number of blood cultures performed, and, importantly, days on antibiotic therapy. Probabilistic and one-way sensitivity analyses showed the model outcome to be robust against changes in model inputs. Conclusion: Proven safe, a PCT algorithm for antibiotic discontinuation is a cost-effective means of reducing antibiotic exposure in adult ICU patients with sepsis, compared to current practice. Additional resources required for PCT are more than offset by downstream cost savings. This finding is highly important given the aim of preventing widespread antibiotic resistance.

Long-term cost–effectiveness of Oncotype DX® versus current clinical practice from a Dutch cost perspective

INTRODUCTION This study analyzes the incremental cost-effectiveness of Oncotype DX(®) testing to support adjuvant chemotherapy recommendations, versus current clinical practice, for patients with estrogen receptor-positive (ER(+)), node-negative or micrometastatic (pN1mic) early-stage breast cancer in The Netherlands. METHODS Markov model projecting distant recurrence, survival, quality-adjusted life years (QALYs) and healthcare costs over a 30-year time horizon. RESULTS Oncotype DX was projected to increase QALYs by 0.11 (0.07-0.58) and costs with €1236 (range: -€142-€1236) resulting in an incremental cost-effectiveness ratio of €11,236/QALY under the most conservative scenario. CONCLUSION Reallocation of adjuvant chemotherapy based on Oncotype DX testing is most likely a cost-effective use of scarce resources, improving long-term survival and QALYs at marginal or lower costs.

Early health economic modelling of single-stage cartilage repair. Guiding implementation of technologies in regenerative medicine.

Both the complexity of clinically applied tissue engineering techniques for articular cartilage repair – such as autologous chondrocyte implantation (ACI) – plus increasing healthcare costs, and market competition, are forcing a shift in focus from two‐stage to single‐stage interventions that are more cost‐effective. Early health economic models are expected to provide essential insight in the parameters driving the cost‐effectiveness of new interventions before they are introduced into clinical practice. The present study estimated the likely incremental cost‐effectiveness ratio (ICER) of a new investigator‐driven single‐stage procedure (IMPACT) compared with both microfracture and ACI, and identified those parameters that affect the cost‐effectiveness. A decision tree with clinical health states was constructed. The ICER was calculated by dividing the incremental societal costs by the incremental Quality Adjusted Life Years (QALYs). Costs were determined from a societal perspective. A headroom analysis was performed to determine the maximum price of IMPACT compared with both ACI and microfracture, assuming a societal willingness to pay (WTP) of €30 000/QALY. One‐way sensitivity analysis was performed to identify those parameters that drive the cost‐effectiveness. The societal costs of IMPACT, ACI and microfracture were found to be €11 797, €29 741 and €6081, respectively. An 8% increase in all utilities after IMPACT changes the ICER of IMPACT vs. microfracture from €147 513/QALY to €28 588/QALY. Compared with ACI, IMPACT is less costly, which is largely attributable to the cell expansion procedure that has been rendered redundant. While microfracture can be considered the most cost‐effective treatment option for smaller defects, a single‐stage tissue engineering procedure can replace ACI to improve the cost‐effectiveness for treating larger defects, especially if clinical non‐inferiority can be achieved. Copyright

Early health economic modelling of single-stage cartilage repair. Guiding implementation of technologies in regenerative medicine

Both the complexity of clinically applied tissue engineering techniques for articular cartilage repair – such as autologous chondrocyte implantation (ACI) – plus increasing healthcare costs, and market competition, are forcing a shift in focus from two‐stage to single‐stage interventions that are more cost‐effective. Early health economic models are expected to provide essential insight in the parameters driving the cost‐effectiveness of new interventions before they are introduced into clinical practice. The present study estimated the likely incremental cost‐effectiveness ratio (ICER) of a new investigator‐driven single‐stage procedure (IMPACT) compared with both microfracture and ACI, and identified those parameters that affect the cost‐effectiveness. A decision tree with clinical health states was constructed. The ICER was calculated by dividing the incremental societal costs by the incremental Quality Adjusted Life Years (QALYs). Costs were determined from a societal perspective. A headroom analysis was performed to determine the maximum price of IMPACT compared with both ACI and microfracture, assuming a societal willingness to pay (WTP) of €30 000/QALY. One‐way sensitivity analysis was performed to identify those parameters that drive the cost‐effectiveness. The societal costs of IMPACT, ACI and microfracture were found to be €11 797, €29 741 and €6081, respectively. An 8% increase in all utilities after IMPACT changes the ICER of IMPACT vs. microfracture from €147 513/QALY to €28 588/QALY. Compared with ACI, IMPACT is less costly, which is largely attributable to the cell expansion procedure that has been rendered redundant. While microfracture can be considered the most cost‐effective treatment option for smaller defects, a single‐stage tissue engineering procedure can replace ACI to improve the cost‐effectiveness for treating larger defects, especially if clinical non‐inferiority can be achieved. Copyright

The effectiveness of a routine versus an extensive laboratory analysis in the diagnosis of anaemia in general practice

Background We investigated the percentage of patients diagnosed with the correct underlying cause of anaemia by general practitioners when using an extensive versus a routine laboratory work-up. Methods An online survey was distributed among 836 general practitioners. The survey consisted of six cases, selected from an existing cohort of anaemia patients (n = 3325). In three cases, general practitioners were asked to select the laboratory tests for further diagnostic examination from a list of 14 parameters (i.e. routine work-up). In the other three cases, general practitioners were presented with all 14 laboratory test results available (i.e. extensive work-up). General practitioners were asked to determine the underlying cause of anaemia in all six cases based on the test results, and these answers were compared with the answers of an expert panel. Results A total of 139 general practitioners (partly) responded to the survey (17%). The general practitioners were able to determine the underlying cause of anaemia in 53% of cases based on the routine work-up, whereas 62% of cases could be diagnosed using an extensive work-up (P = 0.007). In addition, the probability of a correct diagnosis decreased with the patient’s age and was also affected by the underlying cause itself, with anaemia of chronic disease being hardest to diagnose (P = 0.003). Conclusion The use of an extensive laboratory work-up in patients with newly diagnosed anaemia is expected to increase the percentage of correct underlying causes established by general practitioners. Since the underlying cause can still not be established in 31.3% of anaemia patients, further research is necessary.

Assessing the cost-effectiveness of a routine versus an extensive laboratory work-up in the diagnosis of anaemia in Dutch general practice

Background Establishing the underlying cause of anaemia in general practice is a diagnostic challenge. Currently, general practitioners individually determine which laboratory tests to request (routine work-up) in order to diagnose the underlying cause. However, an extensive work-up (consisting of 14 tests) increases the proportion of patients correctly diagnosed. This study investigates the cost-effectiveness of this extensive work-up. Methods A decision-analytic model was developed, incorporating all societal costs from the moment a patient presents to a general practitioner with symptoms suggestive of anaemia (aged ≥ 50 years), until the patient was (correctly) diagnosed and treated in primary care, or referred to (and diagnosed in) secondary care. Model inputs were derived from an online survey among general practitioners, expert estimates and published data. The primary outcome measure was expressed as incremental cost per additional patient diagnosed with the correct underlying cause of anaemia in either work-up. Results The probability of general practitioners diagnosing the correct underlying cause increased from 49.6% (95% CI: 44.8% to 54.5%) in the routine work-up to 56.0% (95% CI: 51.2% to 60.8%) in the extensive work-up (i.e. +6.4% [95% CI: −0.6% to 13.1%]). Costs are expected to increase slightly from €842/patient (95% CI: €704 to €994) to €845/patient (95% CI: €711 to €994), i.e. +€3/patient (95% CI: €−35 to €40) in the extensive work-up, indicating incremental costs of €43 per additional patient correctly diagnosed. Conclusions The extensive laboratory work-up is more effective for diagnosing the underlying cause of anaemia by general practitioners, at a minimal increase in costs. As accompanying benefits in terms of quality of life and reduced productivity losses could not be captured in this analysis, the extensive work-up is likely cost-effective.

Cost-effectiveness analysis evaluating Factor VIII as primary prophylaxis treatment for patients with severe haemophilia A in The Netherlands

PSY57 CoSt EffECtivEnESS AnAlYSiS EvAluAting fACtor viii AS PrimArY ProPhYlAxiS trEAtmEnt for PAtiEntS With SEvErE hAEmoPhiliA A in thE nEthErlAndS Kip M.1, van den Bosch M.2, Fischer K.3, Tamminga R.4, Lepage-Nefkens I.1 1PANAXEA, Enschede, The Netherlands, 2Bayer, Mijdrecht, The Netherlands, 3Van Creveldkliniek & Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands, 4Beatrix Childrens Hospital, University Medical Center Groningen, Groningen, The Netherlands Objectives: Multiple regimens are used in the treatment of severe haemophilia A in the Netherlands. Most patients receive clotting factors intravenously 2-3 times weekly to prevent bleedings: intermediate dose prophylaxis. Given the high utilization of prophylaxis treatment, budget restraints might hinder the availability of prophylaxis for patients in the nearby future. Other treatment regimens are ondemand (OD) treatment, administering clotting factors in case of bleedings, and prophylaxis treatment with a switch to OD at 18 years. This analysis estimates the cost-effectiveness of Dutch prophylaxis treatment for severe haemophilia A patients compared to other treatment regimens. MethOds: A Markov model is developed with the health stages ‘Alive’, ‘Severe joint damage’ and ‘Death’. Bleeding rates of individual patients are simulated over lifetime, including a probability of inhibitor development. A higher joint bleed rate is accompanied by increased joint damage, increasing the chance of joint surgery. Disease progression, within the Alive health state, is modeled with the Pettersson Score (PS). The PS indicates the radiographic arthropathy. Increased joint damage is associated with physical limitations and decreased QoL. Because the chosen treatment regimen affects both the joint bleed rate and inhibitor development, it also affects the HRQoL. The analysis was performed from a societal perspective. Results: Prophylaxis treatment was associated with the greatest QoL. The cost-effectiveness acceptability curve shows a probability of 90% for prophylaxis treatment to be cost-effective at a threshold of € 0, compared to OD treatment. Compared to prophylaxis with a switch to OD at 18 years, prophylaxis treatment has a 50% probability of being cost-effective at a € 80.000, threshold. The model outcome is sensitive for variations in bleeding rate, prophylaxis dosage, inhibitor development and utilities. cOnclusiOns: Based on our model, treatment of severe haemophilia A patients with lifetime prophylaxis is cost-effective compared to OD treatment.