Recent research has employed different analytical techniques to estimate the impact of the various long-term complications of type 2 diabetes on health-related utility and health status. However, limited patient numbers or lack of variety of patient experience has limited their power to discriminate between separate complications and grades of severity. In this study alternative statistical model forms were compared to investigate the influence of various factors on self-assessed health status and calculated utility scores, including the presence and severity of complications, and type of diabetes therapy. Responses to the EuroQol EQ-5D questionnaire from 4641 patients with type 2 diabetes in 5 European countries were analysed. Simple multiple regression analysis was used to model both visual analogue scale (VAS) scores and time trade-off index scores (TTO). Also, two complex models were developed for TTO analysis using a structure suggested by the EuroQol calculation algorithm. Both VAS and TTO models achieved greater explanatory power than in earlier studies. Relative weightings for individual complications differed between VAS and TTO scales, reflecting the strong influence of loss of mobility and severe pain in the EuroQol algorithm. Insulin-based therapy was uniformly associated with a detrimental effect equivalent to an additional moderate complication. Evidence was found that TTO values are not responsive in cases where 3 or more multiple complications are present, and therefore may underestimate utility loss for patients most adversely affected by complex chronic diseases like diabetes.

A recent publication includes a review of survival extrapolation methods used in technology appraisals of treatments for advanced cancers. The author of the article also noted shortcomings and inconsistencies in the analytical methods used in appraisals. He then proposed a survival model selection process algorithm to guide modelers' choice of projective models for use in future appraisals. This article examines the proposed algorithm and highlights various shortcomings that involve questionable assumptions, including researchers' access to patient-level data, the relevance of proportional hazards modeling, and the appropriateness of standard probability functions for characterizing risk, which may mislead practitioners into employing biased structures for projecting limited data in decision models. An alternative paradigm is outlined. This paradigm is based on the primacy of the experimental data and adherence to the scientific method through hypothesis formulation and validation. Drawing on extensive experience of survival modeling and extrapolation in the United Kingdom, practical advice is presented on issues of importance when using data from clinical trials terminated without complete follow-up as a basis for survival extrapolation.

BackgroundThere is no single definitive test to identify prostate cancer in men. Biopsies are commonly used to obtain samples of prostate tissue for histopathological examination. However, this approach frequently misses cases of cancer, meaning that repeat biopsies may be necessary to obtain a diagnosis. The PROGENSA®prostate cancer antigen 3 (PCA3) assay (Hologic Gen-Probe, Marlborough, MA, USA) and the Prostate Health Index (phi; Beckman Coulter Inc., Brea, CA, USA) are two new tests (a urine test and a blood test, respectively) that are designed to be used to help clinicians decide whether or not to recommend a repeat biopsy.ObjectiveTo evaluate the clinical effectiveness and cost-effectiveness of the PCA3 assay and the phi in the diagnosis of prostate cancer.Data sourcesMultiple publication databases and trial registers were searched in May 2014 (from 2000 to May 2014), including MEDLINE, EMBASE, The Cochrane Library, ISI Web of Science, Medion, Aggressive Research Intelligence Facility database, ClinicalTrials.gov, International Standard Randomised Controlled Trial Number Register and World Health Organization International Clinical Trials Registry Platform.Review methodsThe assessment of clinical effectiveness involved three separate systematic reviews, namely reviews of the analytical validity, the clinical validity of these tests and the clinical utility of these tests. The assessment of cost-effectiveness comprised a systematic review of full economic evaluations and the development of a de novo economic model.SettingThe perspective of the evaluation was the NHS in England and Wales.ParticipantsMen suspected of having prostate cancer for whom the results of an initial prostate biopsy were negative or equivocal.InterventionsThe use of the PCA3 score or phi in combination with existing tests (including histopathology results, prostate-specific antigen level and digital rectal examination), multiparametric magnetic resonance imaging and clinical judgement.ResultsIn addition to documents published by the manufacturers, six studies were identified for inclusion in the analytical validity review. The review identified issues concerning the precision of the PCA3 assay measurements. It also highlighted issues relating to the storage requirements and stability of samples intended for analysis using the phi assay. Fifteen studies met the inclusion criteria for the clinical validity review. These studies reported results for 10 different clinical comparisons. There was insufficient evidence to enable the identification of appropriate test threshold values for use in a clinical setting. In addition, the implications of adding either the PCA3 assay or the phi to clinical assessment were not clear. Furthermore, the addition of the PCA3 assay or the phi to clinical assessment plus magnetic resonance imaging was not found to improve discrimination. No published papers met the inclusion criteria for either the clinical utility review or the cost-effectiveness review. The results from the cost-effectiveness analyses indicated that using either the PCA3 assay or the phi in the NHS was not cost-effective.LimitationsThe main limitations of the systematic review of clinical validity are that the review conclusions are over-reliant on findings from one study, the descriptions of clinical assessment vary widely within reviewed studies and many of the reported results for the clinical validity outcomes do not include either standard errors or confidence intervals.ConclusionsThe clinical benefit of using the PCA3 assay or the phi in combination with existing tests, scans and clinical judgement has not yet been confirmed. The results from the cost-effectiveness analyses indicate that the use of these tests in the NHS would not be cost-effective.Study registrationThis study is registered as PROSPERO CRD42014009595.FundingThe National Institute for Health Research Health Technology Assessment programme.

This model may have important implications for targeting appropriate therapy to patients in each phase: delaying or avoiding full clinical type 2 diabetes in the first phase; and preventing the development of diabetic complications in the second phase.