Cost-effectiveness of outpatient parenteral antibiotic therapy: a simulation modelling approach.

Objectives: In the UK, patients who require intravenous antimicrobial (IVA) treatment may receive this in the community through outpatient parenteral antimicrobial therapy (OPAT) services. Services include: IVA administration at a hospital outpatient clinic (HO); IVA administration at home by a general nurse (GN) or a specialist nurse (SN); or patient self-administered (SA) IVA administration following training. There is uncertainty regarding which OPAT services represent value for money; this study aimed to estimate their cost-effectiveness. Methods: A cost-effectiveness decision-analytic model was developed using a simulation technique utilizing data from hospital records and a systematic review of the literature. The model estimates cost per QALY gained from the National Health Service (NHS) perspective for short- and long-term treatment of infections and service combinations across these. Results: In short-term treatments, HO was estimated as the most effective (0.7239 QALYs), but at the highest cost (£973). SN was the least costly (£710), producing 0.7228 QALYs. The combination between SN and HO was estimated to produce 0.7235 QALYs at a cost of £841. For long-term treatments, SN was the most effective (0.677 QALYs), costing £2379, while SA was the least costly at £1883, producing 0.666 QALYs. A combination of SA and SN was estimated to produce 0.672 QALYs at a cost of £2128. Conclusions: SN and SA are cost-effective for short- and long-term treatment of infections, while combining services may represent the second-best alternative for OPAT in the UK.

Costs of cancer care for use in economic evaluation: a UK analysis of patient-level routine health system data.

BACKGROUND: The rising financial burden of cancer on health-care systems worldwide has led to the increased demand for evidence-based research on which to base reimbursement decisions. Economic evaluations are an integral component of this necessary research. Ascertainment of reliable health-care cost and quality-of-life estimates to inform such studies has historically been challenging, but recent advances in informatics in the United Kingdom provide new opportunities. METHODS: The costs of hospital care for breast, colorectal and prostate cancer disease-free survivors were calculated over 15 months from initial diagnosis of cancer using routinely collected data within a UK National Health Service (NHS) Hospital Trust. Costs were linked at patient level to patient-reported outcomes and registry-derived sociodemographic factors. Predictors of cost and the relationship between costs and patient-reported utility were examined. RESULTS: The study population included 223 breast cancer patients, 145 colorectal and 104 prostate cancer patients. The mean 15-month cumulative health-care costs were £12 595 (95% CI £11 517-£13 722), £12 643 (£11 282-£14 102) and £3722 (£3263-£4208), per-patient respectively. The majority of costs occurred within the first 6 months from diagnosis. Clinical stage was the most important predictor of costs for all cancer types. EQ-5D score was predictive of costs in colorectal cancer but not in breast or prostate cancer. CONCLUSION: It is now possible to evaluate health-care cost using routine NHS data sets. Such methods can be utilised in future retrospective and prospective studies to efficiently collect economic data.

The cost-effectiveness of primary care referral to a UK commercial weight loss programme.

Primary care referral to commercial weight loss programmes that follow best practice is included in current UK guidance on the management of adult obesity. This study investigated whether such a programme was cost-effective compared with usual care. A decision-analytical Markov model was developed to estimate the lifetime costs and benefits of the referral programme compared with usual care and enable a cost-utility analysis. The model cohort transited between body mass index classifications and type 2 diabetes, stroke and myocardial infarction (MI) with risk, cost and effect parameter values taken from published literature. The cost per incremental quality-adjusted life year (QALY) was calculated. Extensive deterministic and scenario sensitivity analyses and probabilistic sensitivity analyses (PSA) were conducted. At 12 months, the incremental cost-effectiveness ratio was £6906, indicating that programme referral was cost-effective. Over a lifetime, referral to the commercial programme was dominant as it led to a cost saving of £924 and conferred incremental benefit (0.22 QALY) over usual care. Model simulations estimated lower lifetime rates of type 2 diabetes, stroke and MI as a result of the weight loss achieved. The results were robust to extensive sensitivity analyses. The PSA indicated that programme referral had a 68% chance of being cost-effective at a willingness to pay per incremental QALY threshold of £20,000. Referral to the programme dominated usual care, being both cheaper and more effective. These results compare favourably with economic evaluations of other obesity interventions and add to a growing evidence base on the cost-effectiveness of commercial weight loss providers and practices.

The development and validation of the Unidimensional Fatigue Impact Scale (U-FIS).

BACKGROUND: The multidimensional assessment of fatigue is complicated by the interrelation of its multiple causes and effects. OBJECTIVE: The purpose of the research was to develop a unidimensional assessment of fatigue (U-FIS). METHODS: Data collected with the Fatigue Impact Scale (FIS) were subjected to Rasch analysis to identify potential problems with the scale. Additional items for the U-FIS were generated from interviews with UK MS patients. The U-FIS was tested for face and content validity in patient interviews and included in a validation survey to determine dimensionality (Rasch model), reliability and validity. RESULTS: The original FIS was not unidimensional when subscale items were combined. The modification of the FIS and addition of a number of items allowed the development of a 22-item unidimensional scale (U-FIS) that was reliable (Cronbach Alpha = 0.96; test-retest = 0.86,) and valid given correlations with the Nottingham Health Profile and ability to distinguish between MS severity groups. There was no significant difference in U-FIS scores according to MS type. CONCLUSION: It is valid to conceptualize the functional impact of fatigue as unidimensional. The U-FIS is a reliable and valid questionnaire that will allow the measurement of this construct in clinical studies.

The development of patient-reported outcome indices for multiple sclerosis (PRIMUS).

BACKGROUND: Complex diseases such as multiple sclerosis (MS) present dilemmas over the choice of patient-reported outcome measures as no single scale can inform on all types of MS impact from the patient's perspective. OBJECTIVE: To develop an outcome tool, the Patient-Reported Indices for Multiple Sclerosis (PRIMUS), to assess MS symptoms, activities, and quality of life. METHODS: PRIMUS content was derived from qualitative interviews with UK MS patients and checked by clinical experts. Semi-structured cognitive debriefing interviews assessed scale face and content validity. PRIMUS scaling properties, reliability, and construct validity were assessed by a test-retest postal survey. RESULTS: Cognitive debriefing interviews (n = 15) demonstrated scale clarity, relevance, and comprehensiveness. The postal survey was completed by 135 patients with MS. After removal of misfitting items and those exhibiting differential item functioning, all scales fitted the Rasch model, confirming unidimensionality. For all scales, test-retest reliability exceeded 0.80. Scale scores were related to perceived MS severity, general health, and symptoms of depression. Moderate correlations were observed between PRIMUS and Nottingham Health Profile scores. CONCLUSIONS: Clinicians and researchers can have confidence in scores obtained by respondents on the PRIMUS. The PRIMUS will aid the assessment of the impact of MS from the patient's perspective.

The responsiveness and validity of the CAMPHOR Utility Index.

The aim of the present study was to validate and determine the minimal important difference (MID) and responsiveness of the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) Utility Index, a new tool enabling cost utility analyses. CAMPHOR, 6-min walking test (6MWT) and New York Heart Association (NYHA) data for 869 pulmonary hypertension patients (545 (63%) female; mean+/-SD age 56.6+/-15.4 yrs) from three centres were analysed. Utility was correlated with 6MWT data and calculated by NYHA class to assess validity. Effect sizes were calculated for those with two CAMPHOR assessments. Distribution and anchor-based MIDs were calculated. Analyses were carried out in patients receiving bosentan in order to determine whether or not those remaining in NYHA class III following treatment improved. The Utility Index distinguished between adjacent NYHA classes and correlated with 6MWT results. CAMPHOR subscales and utility were as responsive as the 6MWT (effect sizes ranged 0.31-0.69 for the CAMPHOR and 0.16-0.34 for the 6MWT). The within-group MID for the Utility Index was estimated to be approximately 0.09. Patients remaining in NYHA class III experienced, on average, a significant improvement (CAMPHOR Utility Index and functioning), which exceeded the MID. The CAMPHOR Utility Index is valid and responsive to change. Patients can experience significant and important improvements even if they do not improve on the basis of traditional outcomes, such as NYHA functional class.

Adaptation of the RAQoL for use in Australia.

Quality of life is an important patient-reported outcome of rheumatoid arthritis (RA) in addition to structural and functional outcomes. The RAQoL (Rheumatoid Arthritis Quality of Life questionnaire) was developed in the UK and the Netherlands as a disease-specific tool. It was adapted for use in the Australian social context and the reliability and validity was tested. A lay panel assessed the UK version and adapted the wording for use within Australia. Reliability and validity were assessed by a postal survey of the RAQoL and comparator questionnaires to 100 patients with RA. The RAQoL was easily adapted into Australian-English. Test-retest reliability was high with a Spearman rank correlation coefficient of 0.93. RAQoL scores correlated well with patient-perceived disease activity and severity--indicating good validity. The Australian version of the RAQoL is a valid and reliable tool for the assessment of quality of life. It is practical, easy to administer and has good potential for use in clinical settings and trials in Australia.

The Rheumatoid Arthritis Quality of Life (RAQoL) for Sweden: adaptation and validation.

OBJECTIVE: To produce and evaluate the official Swedish language version of the Rheumatoid Arthritis Quality of Life instrument (RAQoL). METHODS: The UK RAQoL was translated into Swedish by a bilingual translation panel. A separate lay panel was conducted to consider the appropriateness and comprehensibility of the items in Swedish. Interviews were conducted with 15 Swedish RA patients to assess face and content validity. Responses to a postal survey were used to calculate reproducibility and construct validity. RESULTS: Few difficulties arose in the translation process and the new language version was well received by the lay panel and field-test participants. One hundred and sixty-five RA patients participated in the postal survey (69% female; mean age 62.7 years, SD 11.3, RA duration range 1-62 years). Cronbach's alpha for the Swedish RAQoL was 0.91 and test-retest reliability was 0.95, indicating that the instrument has adequate inter-relatedness of items and very low inherent random measurement error. A high correlation with the Health Assessment Questionnaire (HAQ) was observed; this was expected because RA has significant physical manifestations that are in turn a significant determinant of QoL. The Swedish RAQoL was able to distinguish between patients who differed according to their self-perceived RA severity, general health, and rating of their RA today, in addition to whether or not the patient was experiencing a flare of RA. CONCLUSIONS: The official Swedish RAQoL was well received by RA patients. The psychometric quality of the adapted questionnaire means that it is suitable for inclusion in clinical trials involving patients with RA.

The Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR): a measure of health-related quality of life and quality of life for patients with pulmonary hypertension.

OBJECTIVE: No outcome measures specific to pulmonary hypertension (PH) currently exist. The aim of the study was to develop health-related quality of life (symptoms and functioning) scales and a quality of life scale that would allow comprehensive, accurate and valid patient-reported outcome assessment in clinical studies. METHODS: The content of the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) was derived from qualitative interviews conducted with 35 patients. Item reduction was based on the analysis of responses to a postal survey (n=75) and patient interviews (n=15) designed to determine face and content validity. A final postal validation study (n=91) was performed to determine reproducibility and construct validity. RESULTS: The questionnaire was well received by participants who found it to be relevant, comprehensible and quick and easy to complete. Rasch and factor analyses were conducted to ensure unidimensionality of the final CAMPHOR scales; Overall symptoms (made up of Energy, Breathlessness and Mood subscales), Functioning and Quality of life. The CAMPHOR scales had good internal consistency (alpha=0.90-0.92) and reproducibility (test-retest correlations=0.86-0.92). They also exhibited convergent, divergent and known groups validity. CONCLUSIONS: The CAMPHOR is a valuable new instrument for assessing patient-reported outcome in PH clinical trials and routine practice.

Double-blind placebo-controlled study of testosterone patch therapy on bone turnover in men with borderline hypogonadism.

Clinical studies suggest there may be a threshold concentration of serum testosterone below which replacement will result in skeletal and psychological benefit. We evaluated the response to testosterone in men with borderline hypogonadism. A randomized double-blind placebo-controlled trial in 39 men over age 40 years presenting with sexual dysfunction and a borderline low testosterone level (total testosterone <10 nmol/L or free androgen index <30%). Patients were randomized to Testoderm TTS body patch (5 mg/day, n = 20) or a placebo patch (n = 19) for 6 months, followed by open-label testosterone replacement for a further 6 months in all patients. During the placebo-controlled phase of the study serum testosterone increased significantly on testosterone vs. placebo treatment (p = 0.004); this was associated with a decrease in total body fat mass (p = 0.019) and increase in haemoglobin level (p = 0.036). There were no significant changes in lean body mass, markers of bone turnover, and measures of bone mineral density (BMD). There was evidence of difference in quality of life according to the Male Erectile Dysfunction Quality of Life questionnaire (MEDQoL score, p = 0.017), mainly accounted for by deterioration in the placebo arm. When the active treatment period was combined for placebo and testosterone groups, the within-patient analysis showed a significant effect of testosterone to decrease markers of bone resorption (uNTX/Cr, p = 0.007; iFDPD/Cr, p = 0.0006) and to increase lean body mass (p = 0.001). There was little convincing evidence from this study that testosterone replacement is likely to have major benefit in men over age 40 years with borderline hypogonadism and sexual dysfunction. However, there was evidence of suppression in bone resorption and hence longer and larger studies are needed to examine its effect on BMD.

The quality of life of parents of children with atopic dermatitis: interpretation of PIQoL-AD scores.

The PIQoL-AD has been used in several trials assessing quality of life (QoL) in parents of children with atopic dermatitis (AD), treated with pimecrolimus cream 1%. Secondary analysis of data from four trials (n = 621) was undertaken to help interpret the meaningfulness (significance) of the QoL results. A combination of anchor-based and distribution-based methods of interpreting instrument scores were employed. For each level on four AD severity indicators, mean PIQoL-AD scores and 95% confidence intervals were calculated. Low levels of association (r(s) range = 0.12-0.45) were observed between QoL and clinical indicators; confirming previous findings. When data from the different trials and time-points were combined clear patterns emerged indicating the clinical meaning of PIQoL-AD scores. Distribution-based statistics such as effect sizes, the standard error of measurement (SEM) and the standard error of difference (S(diff)) were also calculated. Despite a lack of consensus on how best to determine the meaningfulness of QoL scores, a large database of trial data was successfully used to link QoL scores to disease severity, aiding clinical interpretation of the former. Effect size, SEM and S(diff) values were consistent across the trials indicating that a change of 2 to 3 PIQoL-AD points over time could be considered meaningful. It is argued that it would be useful for clinicians to gain an understanding of the meaning of QoL scores through routine use of such measures in clinical practice.