Challenges for Economic Evaluation of Health Care Strategies to Contain Antimicrobial Resistance.

The threat of antimicrobial resistance has global health and economic consequences. Medical strategies to reduce unnecessary antibiotic prescribing, to conserve the effectiveness of current antimicrobials in the long term, inevitably result in short-term costs to health care providers. Economic evaluations of health care interventions therefore need to consider the short-term costs of interventions, to gain future benefits. This represents a challenge for health economists, not only in terms of the most appropriate methods for evaluation, but also in attributing the potential budget impact over time and considering health impacts on future populations. This commentary discusses the challenge of accurately capturing the cost-effectiveness of health care interventions aimed at tackling antimicrobial resistance. We reflect on methods to capture and incorporate the costs and health outcomes associated with antimicrobial resistance, the appropriateness of the quality-adjusted-life year (QALY), individual time preferences, and perspectives in economic evaluation.

Patient-Focused Drug Development Methods for Benefit-Risk Assessments: A Case Study Using a Discrete Choice Experiment for Antiepileptic Drugs.

Regulatory decisions may be enhanced by incorporating patient preferences for drug benefit and harms. This study demonstrates a method of weighting clinical evidence by patients' benefit-risk preferences. Preference weights, derived from discrete choice experiments, were applied to clinical trial data to estimate the expected utility of alternative drugs. In a case study, the rank ordering of antiepileptic drugs (AEDs), as indicated from clinical studies, was compared with ordering based on weighting clinical evidence by patients' preferences. A statistically significant change in rank ordering of AEDs was observed for women of childbearing potential who were prescribed monotherapy for generalized or unclassified epilepsy. Rank ordering inferred from trial data, valproate > topiramate > lamotrigine, was reversed. Modeling the expected utility of drugs might address the need to use more systematic, methodologically sound approaches to collect patient input that can further inform regulatory decision making.

Cost-Effectiveness Analysis of the Use of Point-of-Care C-Reactive Protein Testing to Reduce Antibiotic Prescribing in Primary Care.

More appropriate and measured use of antibiotics may be achieved using point-of-care (POC) C-reactive protein (CRP) testing, but there is limited evidence of cost-effectiveness in routine practice. A decision analytic model was developed to estimate the cost-effectiveness of testing, compared with standard care, in adults presenting in primary care with symptoms of acute respiratory tract infection (ARTI). Analyses considered (1) pragmatic use of testing, reflective of routine clinical practice, and (2) testing according to clinical guidelines. Threshold and scenario analysis were performed to identify cost-effective scenarios. In patients with symptoms of ARTI and based on routine practice, the incremental cost-effectiveness ratios of CRP testing were £19,705 per quality-adjusted-life-year (QALY) gained and £16.07 per antibiotic prescription avoided. Following clinical guideline, CRP testing in patients with lower respiratory tract infections (LRTIs) cost £4390 per QALY gained and £9.31 per antibiotic prescription avoided. At a threshold of £20,000 per QALY, the probabilities of POC CRP testing being cost-effective were 0.49 (ARTI) and 0.84 (LRTI). POC CRP testing as implemented in routine practice is appreciably less cost-effective than when adhering to clinical guidelines. The implications for antibiotic resistance and Clostridium difficile infection warrant further investigation.

What influences persistence with medicines? A multinational discrete choice experiment of 2549 patients.

AIM: The aim was to examine patients' stated preferences to persist with medicines and to explore the influence of psychosocial and sociocognitive factors. METHODS: Community-dwelling, hypertensive patients recruited from nine European countries were invited to complete a discrete choice experiment (DCE) with attributes for treatment benefits, mild yet common adverse drug reactions (ADRs), rare but potentially life-threatening ADRs and dosing frequency. Patients responded to the binary choice of which medicine would they be most likely to continue taking. Data were analyzed using a random effects logit model. RESULTS: Two thousand five hundred and forty-nine patients from Austria (n = 321), Belgium (n = 175), England (n = 315), Germany (n = 266), Greece (n = 288), Hungary (n = 322), the Netherlands (n = 231), Poland (n = 312) and Wales (n = 319) completed the DCE. All attributes significantly influenced patients' stated preference to persist with medications (P < 0.05). Patients were willing to accept decreases in treatment benefits of 50.6 percentage points (95% CI 46.1, 57.9) for a very rare (as opposed to rare) risk of severe ADR, 28.3 percentage points (95% CI 25.2, 33.1) for a once daily instead of twice daily dosing and 0.74 percentage points (95% CI 0.67, 0.85) for a 1% point reduction in mild ADRs. Models accounting for psychosocial and sociocognitive characteristics were significantly different from the base case. CONCLUSION: Patients' intention to persist with treatment was associated with their willingness to trade potential benefits, harms and dosing frequency. Psychosocial and sociocognitive factors influenced the extent of trading. The utility model may have value in assessing patients' likelihood of persisting with medicines and to tailor treatment to maximize persistence.

Pharmacogenetic testing prior to carbamazepine treatment of epilepsy: patients' and physicians' preferences for testing and service delivery.

AIM: Pharmacogenetic studies have identified the presence of the HLA-A*31:01 allele as a predictor of cutaneous adverse drugs reactions (ADRs) to carbamazepine. This study aimed to ascertain the preferences of patients and clinicians to inform carbamazepine pharmacogenetic testing services. METHODS: Attributes of importance to people with epilepsy and neurologists were identified through interviews and from published sources. Discrete choice experiments (DCEs) were conducted in 82 people with epilepsy and 83 neurologists. Random-effects logit regression models were used to determine the importance of the attributes and direction of effect. RESULTS: In the patient DCE, all attributes (seizure remission, reduction in seizure frequency, memory problems, skin rash and rare, severe ADRs) were significant. The estimated utility of testing was greater, at 0.52 (95% CI 0.19, 1.00) than not testing at 0.33 (95% CI -0.07, 0.81). In the physician DCE, cost, inclusion in the British National Formulary, coverage, negative predictive value (NPV) and positive predictive value (PPV) were significant. Marginal rates of substitution indicated that neurologists were willing to pay £5.87 for a 1 percentage point increase in NPV and £3.99 for a 1 percentage point increase in PPV. CONCLUSION: The inclusion of both patients' and clinicians' perspectives represents an important contribution to the understanding of preferences towards pharmacogenetic testing prior to initiating carbamazepine. Both groups identified different attributes but had generally consistent preferences. Patients' acceptance of a decrease in treatment benefit for a reduced chance of severe ADRs adds support for the implementation of HLA-A*31:01 testing in routine practice.

Predictors of self-reported adherence to antihypertensive medicines: a multinational, cross-sectional survey.

BACKGROUND: Nonadherence to antihypertensive medicines limits their effectiveness, increases the risk of adverse health outcome, and is associated with significant health care costs. The multiple causes of nonadherence differ both within and between patients and are influenced by patients' care settings. OBJECTIVES: The objective of this article was to identify determinants of patient nonadherence to antihypertensive medicines, drawing from psychosocial and economic models of behavior. METHODS: Outpatients with hypertension from Austria, Belgium, England, Germany, Greece, Hungary, The Netherlands, Poland, and Wales were recruited to a cross-sectional online survey. Nonadherence to medicines was assessed using the Morisky Medication Adherence Scale (primary outcome) and the Medication Adherence Rating Scale. Associations with adherence and nonadherence were tested for demographic, clinical, and psychosocial factors. RESULTS: A total of 2595 patients completed the questionnaire. The percentage of patients classed as nonadherent ranged from 24% in The Netherlands to 70% in Hungary. Low age, low self-efficacy, and respondents' perceptions of their illness and cost-related barriers were associated with nonadherence measured on the Morisky Medication Adherence Scale across several countries. In multilevel, multivariate analysis, low self-efficacy (odds ratio = 0.73; 95% confidence interval 0.70-0.77) and a high number of perceived barriers to taking medicines (odds ratio = 1.70; 95% confidence interval 1.38-2.09) were the main significant determinants of nonadherence. Country differences explained 11% of the variance in nonadherence. CONCLUSIONS: Among the variables measured, patients' adherence to antihypertensive medicines is influenced primarily by their self-efficacy, illness beliefs, and perceived barriers. These should be targets for interventions for improving adherence, as should an appreciation of differences among the countries in which they are being delivered.

Predicting adherence to medications using health psychology theories: a systematic review of 20 years of empirical research.

OBJECTIVES: This review sought to identify the empirical evidence for the application of models from sociocognitive theory, self-regulation theory, and social support theory at predicting patient adherence to medications. METHODS: A systematic review of the published literature (1990-2010) using MEDLINE, EMBASE, Cochrane Library, CINAHL, and PsychINFO identified studies examining the application of health psychology theory to adherence to medication in adult patients. Two independent reviewers extracted data on medication, indication, study population, adherence measure, theory, model, survey instruments, and results. Heterogeneity in theoretical model specification and empirical investigation precluded a meta-analysis of data. RESULTS: Of 1756 unique records, 67 articles were included (sociocognitive = 35, self-regulation = 21, social support = 11). Adherence was most commonly measured by self-report (50 of 67). Synthesis of studies highlighted the significance (P ≤ 0.05) of self-efficacy (17 of 19), perceived barriers (11 of 17), perceived susceptibility (3 of 6), necessity beliefs (8 of 9), and medication concerns (7 of 8). CONCLUSIONS: The results of this review provide a foundation for the development of theory-led adherence-enhancing interventions that could promote sustainable behavior change in clinical practice.