A first exploration of the economic consequences of an autonomous surgical robot for lateral skull base surgery: an early health technology assessment.

OBJECTIVES: Lateral skull base procedures, such as translabyrinthine approach (TLA), are challenging. An autonomous surgical robot might be a solution to these challenges. Our aim is to explore in an early phase the economic consequences of an autonomous surgical robot compared with conventional TLA. METHODS: An early decision analytic model was constructed in order to perform a step-wise threshold analyses and a sensitivity analysis to analyze the impact of the several factors on the incremental costs. RESULTS: Using surgical robot results in incremental costs - EUR 5,562 per procedure - compared to conventional TLA. These costs are most reduced by higher number of procedures, followed by lower price of the robot, saved operation time, and reduced risk of complication, respectively. CONCLUSIONS: The incremental costs of using an autonomous surgical robot can be decreased by choosing applications with a high turnover rate, a long operation time, and a high complication rate.

Cost-Effectiveness Analysis of Increased Adalimumab Dose Intervals in Crohn's Disease Patients in Stable Remission: The Randomized Controlled LADI Trial.

BACKGROUND AND AIMS: We aimed to assess cost-effectiveness of increasing adalimumab dose intervals compared to the conventional dosing interval in patients with Crohn's disease [CD] in stable clinical and biochemical remission. DESIGN: We conducted a pragmatic, open-label, randomized controlled non-inferiority trial, comparing increased adalimumab intervals with the 2-weekly interval in adult CD patients in clinical remission. Quality of life was measured with the EQ-5D-5L. Costs were measured from a societal perspective. Results are shown as differences and incremental net monetary benefit [iNMB] at relevant willingness to accept [WTA] levels. RESULTS: We randomized 174 patients to the intervention [n = 113] and control [n = 61] groups. No difference was found in utility (difference: -0.017, 95% confidence interval [-0.044; 0.004]) and total costs (-€943, [-€2226; €1367]) over the 48-week study period between the two groups. Medication costs per patient were lower (-€2545, [-€2780; -€2192]) in the intervention group, but non-medication healthcare (+€474, [+€149; +€952]) and patient costs (+€365 [+€92; €1058]) were higher. Cost-utility analysis showed that the iNMB was €594 [-€2099; €2050], €69 [-€2908; €1965] and -€455 [-€4,096; €1984] at WTA levels of €20 000, €50 000 and €80 000, respectively. Increasing adalimumab dose intervals was more likely to be cost-effective at WTA levels below €53 960 per quality-adjusted life year. Above €53 960 continuing the conventional dose interval was more likely to be cost-effective. CONCLUSION: When the loss of a quality-adjusted life year is valued at less than €53 960, increasing the adalimumab dose interval is a cost-effective strategy in CD patients in stable clinical and biochemical remission. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, number NCT03172377.

The added value of predictive biomarkers in treat-to-target strategies for rheumatoid arthritis patients: a conceptual modelling study.

OBJECTIVES: To quantify the additional value of a hypothetical biomarker predicting response to treatment for RA regarding efficacy and costs by using a modelling design. METHODS: A Markov model was built comparing a usual care T2T strategy with a biomarker-steered strategy for RA patients starting biologic therapy. Outcome measures include time spent in remission or low disease activity (LDA) and costs. Four additional scenario analyses were performed by varying biomarker or clinical care characteristics: (i) costs of the biomarker; (ii) sensitivity and specificity of the biomarker; (iii) proportion of eligible patients tapering; and (iv) medication costs. RESULTS: In the base model, patients spent 2.9 months extra in LDA or remission in the biomarker strategy compared with usual care T2T over 48 months. Total costs were €43 301 and €42 568 for, respectively, the usual care and biomarker strategy, and treatment costs accounted for 91% of total costs in both scenarios. Cost savings were driven due to patients in the biomarker strategy experiencing remission or LDA earlier, and starting tapering sooner. Cost-effectiveness was not so much driven by costs or test characteristics of the biomarker (scenario 1/2), but rather by the level of early and proactive tapering and drug costs (scenarios 3/4). CONCLUSIONS: The use of a biomarker for prediction of response to b/tsDMARD treatment in RA can be of added value to current treat-to-target clinical care. However, gains in efficacy are modest and cost gains are depending on a combination of early proactive tapering and high medication costs.

The socioeconomic burden of facioscapulohumeral muscular dystrophy.

BACKGROUND: Promising genetic therapies are being investigated in facioscapulohumeral muscular dystrophy (FSHD). However, the current cost of illness is largely unknown. OBJECTIVE: This study aimed at determining the socioeconomic burden of FSHD. METHODS: Adult patients with FSHD from the Dutch FSHD registry were invited to complete a questionnaire on medical consumption, work productivity and health-related quality of life (HR-QoL) using the EQ-5D-5L. Associated costs were calculated from a societal perspective. A generalized linear model was fitted to the data to investigate whether level of mobility was related to annual costs of illness. RESULTS: 172 patients with FSHD completed the questionnaire (response rate 65%). The per-patient annual direct medical costs of FSHD were estimated at €12,077, direct non-medical costs at €9179 and indirect costs at €5066, adding up to a total cost of illness of €26,322 per patient per year. The direct costs of illness were €21,256, approximately five times higher than the mean per-capita health expenditures in the Netherlands. Major cost-driving factors were formal home care and informal care. A decreased level of mobility was associated with higher direct costs of illness. HR-QoL was significantly reduced in patients with FSHD with a median health utility value of 0.63. CONCLUSIONS: We show that FSHD is associated with substantial direct and indirect socioeconomic costs as well as a reduction in HR-QoL. These findings are important for health care decision makers and aids in allocation of research funds and evaluation of the cost-effectiveness of novel therapies.

The potential of individualized dosing of ravulizumab to improve patient-friendliness of paroxysmal nocturnal haemoglobinuria treatment at reduced costs.

Ravulizumab is a very expensive complement C5-inhibitor for the treatment of paroxysmal nocturnal haemoglobinuria, with a fixed-dosing interval of 8 weeks. For lifelong treatment, a cost-effective and patient-friendly dosing strategy is preferred. We therefore explored alternative ravulizumab dosing regimens in silico based on the thorough dose-finding studies of the manufacturer. Extending the interval to 10 weeks or individually extending the interval to a mean of 12.8 weeks based on pharmacokinetic monitoring resulted in noninferior efficacy in terms of lactate dehydrogenase normalization, with drug cost savings up to 37%. We here show the potential of individualized ravulizumab dosing to improve patient-friendliness at reduced costs.

Health Economic Consequences of a Tightly Controlled Dose Reduction Strategy for Adalimumab, Etanercept and Ustekinumab Compared with Standard Psoriasis Care: A Cost-utility Analysis of the CONDOR Study.

A dose reduction strategy for adalimumab, etanercept and ustekinumab in patients with psoriasis who have stable and low disease activity has recently been compared with usual care in the CONDOR study (CONtrolled DOse Reduction) of biologics in patients with psoriasis with low disease activity. The aim of the current study was to perform a cost-utility analysis with a 12-month time horizon alongside this trial, using prospectively measured healthcare costs and quality-adjusted life years, based on Short-Form Six-Dimension utilities. Bootstrap analys-es were used to calculate the decremental cost-utility ratio and the incremental net monetary benefit. The dose reduction strategy resulted in a mean cost saving of €3,820 (95th percentile -€3,099 to -€4,509) per patient over a period of 12 months. There was an 83% chance that dose reduction would result in a reduction in quality adjusted life years (mean -0.02 (95th percentile -0.06 to 0.02). In conclusion, dose reduction of biologics resulted in substantial cost savings with an acceptable reduction in quality of life.

Correction to: Cost-Utility and Budget Impact Analysis for Stopping the Inappropriate Use of Proton Pump Inhibitors After Cessation of NSAID or Low­Dose Acetylsalicylic Acid Treatment.

Errors were subsequently identified in the article, and the following corrections should be noted.

Cost-Utility and Budget Impact Analysis for Stopping the Inappropriate Use of Proton Pump Inhibitors After Cessation of NSAID or Low-Dose Acetylsalicylic Acid Treatment.

BACKGROUND: In accordance with current guidelines, proton pump inhibitors (PPIs) are now generally prescribed as a protective co-medication in patients taking non-steroidal anti-inflammatory drugs (NSAIDs) or low-dose acetylsalicylic acid (LDASA). However, less attention is paid to the corresponding discontinuation of a PPI after cessation of NSAID or LDASA treatment. OBJECTIVE: The aim of this study was to assess the extent of inappropriate PPI use, as the proportion of patients who started a PPI as a protective co-medication but continued using these drugs after cessation of NSAID and LDASA treatment. We also sought to estimate the potential cost savings and effect gains of discontinuing inappropriate PPI use and the resulting decrease in adverse effects and their detrimental consequences. METHODS: Pharmacy dispensing data were used to map inappropriate PPI use in 2014 for community-dwelling patients. Strategies with or without PPI continuation were compared in the cost-utility analysis for a time horizon of 5 years from a healthcare perspective. Subsequently, incremental costs and effects (quality-adjusted life-years) were estimated with a Markov model. RESULTS: Related to NSAID and LDASA treatment, 11.0% and 5%, respectively, of the PPI users were found to inappropriately continue PPI co-treatment. Discontinuation in 71- to 80-year-old patients suggested cost savings of €170.46 (95% confidence interval 75-282) at a 0.003 (95% confidence interval 0.001-0.005) quality-adjusted life-year increase. The total budget impact of stopping inappropriate PPI use related to NSAID/LDASA treatment in the Netherlands would amount to almost €1,050,000 after 1 year. Correspondingly, successful interventions to stop a patient's inappropriate use would cost up to €29 and probably would pay for themselves in the following years. CONCLUSIONS: A substantial number of patients inappropriately continue to use a PPI after cessation of NSAID or LDASA treatment. Because adverse effects and their detrimental consequences are avoided, interventions to stop inappropriate PPI use, particularly in older patients, are likely to pay for themselves.

Long-term efficacy and cost-effectiveness of blended cognitive behavior therapy for high fear of recurrence in breast, prostate and colorectal Cancer survivors: follow-up of the SWORD randomized controlled trial.

BACKGROUND: Blended cognitive behaviour therapy (bCBT) is an effective treatment for fear of cancer recurrence (FCR) in curatively-treated breast, colorectal and prostate cancer survivors with high FCR. However, long-term outcomes are unknown. This study investigated the long-term efficacy and cost-effectiveness of bCBT compared with care as usual (CAU). METHODS: Eighty-eight cancer survivors with high FCR (Cancer Worry Scale ≥14) were randomly assigned to bCBT (n = 45) or CAU (n = 43). Data were collected at baseline and at three, nine and fifteen months from baseline and analysed by modified intention-to-treat. Efficacy was investigated with linear mixed-effects models. Cost-effectiveness was investigated from a societal perspective by comparing costs with quality-adjusted life-years (QALYs). RESULTS: Participants who received bCBT reported significantly lower FCR compared with CAU (mean difference of - 1.787 [95% CI -3.251 to - 0.323, p = 0.017] at 15 months follow-up), and proportionally greater self-rated and clinically significant improvement at each follow-up measurement. Total QALYs were non-significantly different between conditions when adjusted for utility score baseline differences (0.984 compared to 0.957, p = 0.385), while total costs were €631 lower (95% CI -1737 to 2794, p = 0.587). Intervention costs of bCBT were €466. The incremental cost-effectiveness ratio amounted to an additional €2049 per QALY gained, with a 62% probability that bCBT is cost-effective at a willingness to pay (WTP) threshold of €20,000 per QALY. Results were confirmed in sensitivity analyses. CONCLUSIONS: bCBT for cancer survivors with FCR is clinically and statistically more effective than CAU on the long-term. In addition, bCBT is a relatively inexpensive intervention with similar costs and QALYs as CAU. TRIAL REGISTRATION: The RCT was registered in the Dutch National Trial Register ( NTR4423 ) on 12-Feb-2014. This abstract was previously presented at the International Psycho-Oncology Society conference of 2018 and published online. (Psycho-oncology, 27(S3):8-55; 2018).

Optimizing the dose in patients treated with imatinib as first line treatment for gastrointestinal stromal tumours: A cost-effectiveness study.

AIMS: Patients with metastatic gastrointestinal stromal tumours (GIST) are treated in first line with the oral tyrosine kinase inhibitor, imatinib, until progressive disease. With this fixed dosing regimen, only approximately 40% of patients reach adequate plasma levels within the therapeutic index. Therapeutic drug monitoring (TDM) is a solution to reach plasma levels within the therapeutic index. However, introducing TDM will also increase costs, due to prolonged imatinib use and laboratory costs. The aim of this study was to evaluate the cost-effectiveness of TDM in patients with metastatic/unresectable GIST treated with imatinib as a first line treatment, compared with fixed dosing. METHODS: A survival model was created to simulate progression, mortality and treatment costs over a 5-year time horizon, comparing fixed dosing vs TDM-guided dosing. The outcomes measured were treatments costs, life-years and quality-adjusted life-years. RESULTS: Total costs over the 5-year time horizon were estimated to be €106 994.85 and €150 477.08 for fixed dosing vs TDM-guided dosing, respectively. A quality-adjusted life year gain of 0.74 (95% confidence interval 0.66-0.90) was estimated with TDM-guided dosing compared to fixed dosing. An average incremental cost-effectiveness ratio of €58 785.70 per quality-adjusted life year gained was found, mainly caused by longer use and higher dosages of imatinib. CONCLUSION: Based on the currently available data, this analysis suggests that TDM-guided dosing may be a cost-effective intervention for patients with metastatic/unresectable GIST treated with imatinib which will be improved when imatinib losses its patency.

Genotype-Guided Thiopurine Dosing Does not Lead to Additional Costs in Patients With Inflammatory Bowel Disease.

BACKGROUND AND AIMS: Decreased thiopurine S-methyltransferase [TPMT] enzyme activity increases the risk of haematological adverse drug reactions [ADRs] in patients treated with thiopurines. Clinical studies have shown that in patients with inflammatory bowel disease [IBD], pharmacogenetic TPMT-guided thiopurine treatment reduces this risk of ADRs. The aim of this study was to investigate whether this intervention impacts on healthcare costs and/or quality of life. METHODS: An a priori defined cost-effectiveness analysis was conducted in the Thiopurine response Optimization by Pharmacogenetic testing in Inflammatory bowel disease Clinics [TOPIC] trial, a randomized controlled trial performed in 30 Dutch hospitals. Patients diagnosed with IBD [age ≥18 years] were randomly assigned to the intervention [i.e. pre-treatment genotyping] or control group. Total costs in terms of volumes of care, and effects in quality-adjusted life years [QALYs], based on EuroQol-5D3L utility scores, were measured for 20 weeks. Mean incremental cost savings and QALYs with confidence intervals were calculated using non-parametric bootstrapping with 1000 replications. RESULTS: The intervention group consisted of 381 patients and the control group 347 patients. The mean incremental cost savings were €52 per patient [95% percentiles -682, 569]. Mean incremental QALYs were 0.001 [95% percentiles -0.009, 0.010]. Sensitivity analysis showed that the results were robust for potential change in costs of screening, costs of biologicals and costs associated with productivity loss. CONCLUSIONS: Genotype-guided thiopurine treatment in IBD patients reduced the risk of ADRs among patients carrying a TPMT variant, without increasing overall healthcare costs and resulting in comparable quality of life, as compared to standard treatment.

An economic model of the cost-utility of pre-emptive genetic testing to support pharmacotherapy in patients with major depression in primary care.

The pharmacokinetics of many antidepressants (tricyclic antidepressants (TCA) or selective serotonin re-uptake inhibitors (SSRI)) are influenced by the highly polymorphic CYP2D6 enzyme. Therefore, pharmacogenetics could play an important role in the treatment of depressive patients. The potential cost-utility of screening patients is however still unknown. Therefore, a Markov model was developed to compare the strategy of screening for CYP2D6 and subsequently adjust antidepressant treatment according to a patient's metabolizer profile of poor, extensive, or ultra metabolizer, with the strategy of no screening ('one size fits all' principle). Each week a patient had a probability of side effects, which was followed by dosage titration or treatment switching. After 6 weeks treatment effect was evaluated followed by treatment adjustments if necessary, with a total time horizon of the model of 12 weeks. The analysis was performed from a societal perspective. The strategy of screening compared with no screening resulted in incremental costs of €91 (95 percentiles: €39; €152) more expensive but also more effect with 0.001 quality adjusted life years (QALYs) (95 percentiles: 0.001; 0.002) gain. The incremental cost-effectiveness ratio (ICER) was therefore €77,406 per QALY gained, but varied between €22,500 and €377,500 depending on the price of screening and productivity losses. According to our model, we cannot unequivocally conclude that screening for CYP2D6 in primary care patients using antidepressants is be cost-effective, as the results are surrounded by large uncertainty. Therefore, information from ongoing studies should be used to reduce these uncertainties.

Endosheath ultrathin transnasal endoscopy is a cost-effective method for screening for Barrett's esophagus in patients with GERD symptoms.

BACKGROUND AND AIMS: Barrett's esophagus (BE) screening is currently not considered to be cost effective in the general population but may be effective in high-risk subgroups, such as 50-year-old white men with chronic reflux disease (GERD). A new modality for screening is unsedated transnasal endoscopy using endosheath technology (uTNE), which has been shown to be safe and effective in clinical practice. In this study, we determined the cost-utility of uTNE in a high-risk subgroup compared with no screening or screening with standard endoscopy. METHODS: A Markov model was used to simulate screening of 50-year-old white men with symptoms of GERD with either uTNE or standard endoscopy compared with no screening, over a lifetime horizon. Input variables were based on the literature and recent data on uTNE screening for BE. The study was designed from a healthcare payer perspective by using direct costs. Primary outcome measures were costs, quality-adjusted life years (QALYs), and the incremental cost-utility ratio (ICUR) of uTNE and standard endoscopy compared with no screening. Sensitivity analysis was performed for several factors, such as prevalence of BE. RESULTS: Costs of uTNE, standard endoscopy, and no screening were estimated at, $2495, $2957, and $1436, respectively. Compared with no screening, uTNE screening resulted in an overall QALY increase of 0.039 (95% percentile 0.018; 0.063) and an ICUR of $29,446 per QALY gained (95% confidence interval [CI], 18.516-53.091), whereas standard endoscopy compared with no screening resulted in a QALY increase of 0.034 (95% CI, 0.015-0.056) and an ICUR of $47,563 (95% CI, 31,036-82,970). CONCLUSION: Both uTNE and standard endoscopy seem to be cost-effective screening methods in a screening cohort of 50-year-old white men with GERD at a willingness-to-pay cutoff of $50,000.

Cost-Effectiveness Analysis of Genotype-Guided Treatment Allocation in Patients with Alcohol Use Disorders Using Naltrexone or Acamprosate, Using a Modeling Approach.

Alcohol use disorders (AUD) are a major contributor to the global burden of disease, and have huge societal impact. Some studies show that AUD patients carrying the G-allele of the OPRM1 variant c.118A>G respond better to naltrexone, resulting in reduced relapse rates compared to carriers of the AA genotype. Genotype-guided treatment allocation of these patients carrying a G-allele to naltrexone could potentially improve the treatment outcome. However, cost-effectiveness of this strategy should be investigated before considering clinical implementation. We, therefore, evaluated costs and Quality-Adjusted Life-Years (QALYs), using a modelling approach, from an European perspective, of genotype-guided treatment allocation (G-allele carriers receiving naltrexone; AA homozygotes acamprosate or naltrexone) compared to standard care (random treatment allocation to acamprosate or naltrexone), by using a Markov model. Genotype-guided treatment allocation resulted in incremental costs of EUR 66 (95% CI -28 to 149) and incremental effects of 0.005 QALYs (95% CI 0.000-0.011) per patient (incremental cost-effectiveness ratio of EUR 13,350 per QALY). Sensitivity analyses showed that the risk ratio to relapse after treatment allocation had the largest impact on the cost-effectiveness. Depending on the willingness to pay for a gain of one QALY, probabilities that the intervention is cost-effective varies between 6 and 79%. In conclusion, pharmacogenetic treatment allocation of AUD patients to naltrexone, based on OPRM1 genotype, can be a cost-effective strategy, and could have potential individual and societal benefits. However, more evidence on the impact of genotype-guided treatment allocation on relapse is needed to substantiate these conclusions, as there is contradictory evidence about the effectiveness of OPRM1 genotyping.

Tailored, Therapist-Guided Internet-Based Cognitive Behavioral Therapy Compared to Care as Usual for Patients With Rheumatoid Arthritis: Economic Evaluation of a Randomized Controlled Trial.

BACKGROUND: Internet-based cognitive behavioral therapy can aid patients with rheumatoid arthritis with elevated levels of distress to enhance their quality of life. However, implementation is currently lacking and there is little evidence available on the (cost-) effectiveness of different treatment strategies. OBJECTIVE: Cost-benefit ratios are necessary for informing stakeholders and motivating them to implement effective treatment strategies for improving health-related quality of life (HRQoL) of patients with rheumatoid arthritis. A cost-effectiveness study from a societal perspective was conducted alongside a randomized controlled trial on a tailored, therapist-guided internet-based cognitive behavioral therapy (ICBT) intervention for patients with rheumatoid arthritis with elevated levels of distress as an addition to care as usual (CAU). METHODS: Data were collected at baseline or preintervention, 6 months or postintervention, and every 3 months thereafter during the 1-year follow-up. Effects were measured in terms of quality-adjusted life years (QALYs) and costs from a societal perspective, including health care sector costs (health care use, medication, and intervention costs), patient travel costs for health care use, and costs associated with loss of labor. RESULTS: The intervention improved the quality of life compared with only CAU (Δ QALYs=0.059), but at a higher cost (Δ=€4211). However, this increased cost substantially reduced when medication costs were left out of the equation (Δ=€1863). Of all, 93% (930/1000) of the simulated incremental cost-effectiveness ratios were in the north-east quadrant, indicating a high probability that the intervention was effective in improving HRQoL, but at a greater monetary cost for society compared with only CAU. CONCLUSIONS: A tailored and guided ICBT intervention as an addition to CAU for patients with rheumatoid arthritis with elevated levels of distress was effective in improving quality of life. Consequently, implementation of ICBT into standard health care for patients with rheumatoid arthritis is recommended. However, further studies on cost reductions in this population are warranted. TRIAL REGISTRATION: Nederlands Trial Register NTR2100; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2100 (Archived by WebCite at http://www.webcitation.org/724t9pvr2).

Development and Validation of a Patient-Reported Outcome Measurement for Symptom Assessment in Cirrhotic Ascites.

OBJECTIVES: As current treatments of cirrhotic ascites are not associated with survival benefit, symptom relief is the major therapeutic end point. We developed a questionnaire (Ascites-Q; modified polycystic liver disease questionnaire) and assessed validity and responsiveness for symptom assessment in cirrhotic ascites. METHODS: Ascites-Q was compared with Functional Assessment of Chronic Illness Therapy-Ascites Index (FACIT-AI; developed for malignant ascites) and Japanese Ascites Symptom Inventory-7 (ASI-7) in cirrhotics undergoing large-volume paracentesis. Convergent validity was defined as correlation >0.4 between ascites questionnaires and quality of life (QoL) visual analog scale. Responsiveness was assessed by comparing scores at baseline and 7 days after large-volume paracentesis. To test discriminative ability, we compared scores of patients with cirrhotic controls without ascites (n=24) and diuretic-sensitive ascites (n=46). RESULTS: We included 90 patients with refractory cirrhotic ascites (61% male, mean age 59 years, Model of End-Stage Liver Disease (MELD) score 16, median paracentesis volume 4,100 ml). Higher symptoms scores were correlated with lower QoL (Ascites-Q: r=0.479, P<0.001, FACIT-AI: r=0.313, P=0.007; ASI-7: r=0.340, P=0.004), but only Ascites-Q showed convergent validity (r>0.4). Symptoms decreased after paracentesis (Ascites-Q: 57 to 34, FACIT-AI: 44 to 33, and ASI-7: 57 to 25, all P<0.001). Ascites-Q and ASI-7 discriminated between controls without ascites, diuretic-sensitive, and refractory ascites (Ascites-Q: 16 vs. 35 vs. 56 points, ASI-7: 2 vs. 25 vs. 61 points, all P<0.05), whereas FACIT-AI (39 vs. 40 vs. 52 points) could not (P=0.314). Ascites-Q was validated at 3 months in an independent cohort with ascites controlled with a pump. CONCLUSIONS: The Ascites-Q is the best ascites-specific outcome to evaluate symptom relief in cirrhotic ascites.

THE ADDED VALUE OF INTEGRATE-HTA GUIDANCE IN THE WORK PROCESSES OF HEALTH TECHNOLOGY ASSESSMENT AGENCIES.

A central idea underlying the INTEGRATE-HTA project is that many of the interventions that are being used in health care are quite complex. By this, we mean that the relation between the delivery of the intervention on the one hand, and the onset of (desired and undesired) changes may be less straightforward than hoped for. There may be all sorts of reasons for this, varying from a lack of resources, lack of skills, perverse incentives, organizational problems, etc. Not identifying such factors and their potential impact may seriously compromise the policy relevance of a health technology assessment (HTA) (1). However, current approaches and methods in HTA do not seem to be adequately geared to deal with this complexity.

TAKING PATIENT HETEROGENEITY AND PREFERENCES INTO ACCOUNT IN HEALTH TECHNOLOGY ASSESSMENTS.

OBJECTIVES: The INTEGRATE-HTA project provided methodology to evaluate complex technologies. This study provides guidance on how to retrieve and critically appraise available evidence on moderators and predictors of treatment effects and on patient preferences for treatment outcomes as a source of complexity. METHODS: Search filters for PubMed were developed by hand-searching a large volume of articles reporting on relevant aspects. Search terms were retrieved from selected papers and algorithmically combined to find the optimal combination of search terms. For the development of the appraisal checklists literature was searched in PubMed and Google Scholar together with citation chasing. For the CHecklist for the Appraisal of Moderators and Predictors (CHAMP) a Delphi procedure was used to value a set of eligible appraisal criteria retrieved from the literature. RESULTS: Search filters were developed optimized for different accuracy measures. The final version of CHAMP consists of a seventeen questions covering the design, analysis, results and transferability of results of moderator and predictor analysis. The final checklist for appraisal of literature on patient preferences for treatment outcomes consist of six questions meant to help the user to identify relevant quality issues together with a guidance toward existing tools concerning the appraisal of specific preference elicitation methods. CONCLUSIONS: Incorporating knowledge on subgroups for whom a specific treatment will produce more benefit holds the promise of better targeting and, ultimately, enhancing overall effectiveness and efficiency of healthcare technology. Finally, incorporating information on preferences for treatment outcomes will foster health technology assessment that addresses outcomes that are important to patients.