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J Dinnes

Publications and source records attributed to J Dinnes.

12 recordsLinked to original sources
PubMed2005

Clinical effectiveness and cost-effectiveness of drotrecogin alfa (activated) (Xigris) for the treatment of severe sepsis in adults: a systematic review and economic evaluation.

OBJECTIVES: To assess the clinical and cost-effectiveness of drotrecogin alfa (activated) for the treatment of adults with severe sepsis in a UK context. DATA SOURCES: Electronic databases. Data from the commercial use of the drug up to April 2002. Data from the manufacturer submission to the National Institute for Clinical Excellence (NICE). REVIEW METHODS: A systematic review of the literature and an economic evaluation were undertaken. Data were synthesised through a narrative review with full tabulation of results from included studies. RESULTS: The evidence on the effectiveness of drotrecogin alfa (activated) for the treatment of severe sepsis came primarily from one large pivotal randomised controlled trial, the PROWESS study. This study demonstrated a statistically significant absolute reduction in 28-day mortality of 6.5%. Longer term survival benefit was maintained to 90 days. By 9 months, the trend towards increased median survival was non-significant, although the survival curves did not cross. Results presented by the number of organ dysfunctions were not statistically significant, but when mortality rates for those with two or more organ failures were combined, the relative risk of death was significantly lower in those treated with drotrecogin alfa (activated) compared with placebo. However, this report highlights a number of considerations relevant to the subgroup analyses reported for the PROWESS study. Published cost-effectiveness studies of treatment with drotrecogin alfa (activated) have applied a range of methods to the estimation of benefits, estimating an incremental gain per treated patient of between 0.38 and 0.68 life-years (for patients with severe sepsis). For patients with severe sepsis and multiple organ dysfunction, the manufacturer (Eli Lilly) estimated an incremental gain of 1.115 life-years per treated patient, compared to 1.351 life-years per treated patient estimated by the Southampton Health Technology Assessments Centre (SHTAC). These latter UK analyses are based on a patient group that is more severely affected by disease, where effectiveness is greater and the baseline risk of all-cause mortality is much higher (SHTAC analysis), these factors are associated with the noted difference in effect. The three published cost-effectiveness studies report cost for US and Canadian patient groups; for those patients with severe sepsis they report the additional cost per patient treated in a range around 10,000-16,000 dollars. The manufacturer's submission reports analysis for the UK, based on 28-day survival data in patients with severe sepsis and multiple organ dysfunction (the European licence indication), with the additional mean cost per treated patient estimated to be 5106 pounds. The analysis undertaken by SHTAC, for a UK group of patients with severe sepsis and multiple organ dysfunction, estimates an additional mean cost per patient treated of 6661 pounds. The manufacturer's submission to NICE presents cost-effectiveness estimates for drotrecogin alfa (activated) in the UK, in patients with severe sepsis and multiple organ dysfunction, at 6637 pounds per quality-adjusted life-year (QALY) based on 28-day effectiveness data, and 10,937 pounds per QALY based on longer term follow-up data. SHTAC developed an independent cost-effectiveness model and estimated a base-case cost per QALY of 8228 pounds in patients with severe sepsis and multiple organ failure (based on 28-day survival data). Simulation results indicate that where the NHS is willing to pay 20,000 pounds per QALY, drotrecogin alfa (activated) is a cost-effective use of resources in 98.7% of cases. Published economic evaluations report various sensitivity analyses, with results sensitive to changes in the measure of treatment effect, but otherwise studies reported that results were robust to variations in most assumptions used in the cost-effectiveness analysis. CONCLUSIONS: Drotrecogin alfa (activated) plus best supportive care appears clinically and cost-effective compared with best supportive care alone, in a UK cohort of severe sepsis patients, and in the subgroup of more severely affected patients with severe sepsis and multiple organ failure. The introduction of drotrecogin alfa (activated) will involve a substantial additional cost to the NHS. The treatment-eligible population in England and Wales may comprise up to 16,570 patients, with an estimated annual drug acquisition cost of over 80 million pounds, excluding VAT. Further research is required on the longer term impact of drotrecogin alfa (activated) on both mortality and morbidity in UK patients with severe sepsis, on the clinical and cost-effectiveness of drotrecogin alfa (activated) in children (under 18 years) with severe sepsis, and on the effect of the timing of dosage and duration of treatment on outcomes in severe sepsis.

Adolescent↗
PubMed2005

A methodological review of how heterogeneity has been examined in systematic reviews of diagnostic test accuracy.

OBJECTIVES: To review how heterogeneity has been examined in systematic reviews of diagnostic test accuracy studies. DATA SOURCES: Centre for Reviews and Dissemination's Database of Abstracts of Reviews of Effects (DARE). REVIEW METHODS: Systematic reviews that evaluated a diagnostic or screening test by including studies that compared a test with a reference test were identified from DARE. Reviews for which structured abstracts had been written up to December 2002 were screened for inclusion. Data extraction was undertaken using standardised data extraction forms. RESULTS: A total of 189 systematic reviews met the inclusion criteria. The median number of studies included was 18. Meta-analyses have a higher number with a median of 22 studies compared with 11 for narrative reviews. Graphical plots to demonstrate the spread in study results were provided in 56% of meta-analyses; in 79% these were plots of sensitivity and specificity in the receiver operating characteristic (ROC) space. Statistical tests to identify heterogeneity were used in 32% of reviews: 41% of meta-analyses and 9% of reviews using narrative syntheses. The chi-squared test and Fisher's exact test to assess heterogeneity in individual aspects of test performance were the most common. In contrast, only 16% of meta-analyses used correlation coefficients to test for a threshold effect. A narrative synthesis was used in 30% of reviews. Of the meta-analyses, 52% carried out statistical pooling alone, 18% conducted only summary receiver operator characteristic (SROC) analyses and 30% used both methods of statistical synthesis. For those undertaking SROC analyses, the main differences between the models used were the weights chosen for the regression models, although in 42% of cases the use of, or choice of, weight was not provided. The proportion of reviews using statistical pooling alone has declined from 67% in 1995 to 42% in 2001, with a corresponding increase in the use of SROC methods, from 33% to 58%. However, two-thirds of those using SROC methods also carried out statistical pooling rather than presenting only SROC models. Reviews using SROC analyses also tended to present their results as some combination of sensitivity and specificity rather than using alternative, perhaps less clinically meaningful, means of data presentation such as diagnostic odds ratios. Three-quarters of meta-analyses attempted to investigate statistically possible sources of variation, using subgroup analysis or regression analysis. The impact of clinical or socio-demographic variables was investigated in 74% of these reviews and test- or threshold-related variables in 79%. At least one quality-related variable was investigated in 63% of reviews. Within this subset, the most commonly considered variables were the use of blinding, sample size, the reference test used and the avoidance of verification bias. CONCLUSIONS: The emphasis on pooling individual aspects of diagnostic test performance and the under-use of statistical tests and graphical approaches to identify heterogeneity perhaps reflect the uncertainty in the most appropriate methods to use and also greater familiarity with more traditional indices of test accuracy. This indicates the difficulty and complexity of carrying out such reviews. In these cases it is strongly suggested that meta-analyses are carried out with the involvement of a statistician familiar with the field. Further methodological work on the statistical methods available for combining diagnostic test accuracy studies is needed, as are sufficiently large, prospectively designed primary studies of diagnostic test accuracy comparing two or more tests for the same target disorder. Use of individual patient data meta-analysis in diagnostic test accuracy reviews should be explored to allow heterogeneity to be considered in more detail.

Diagnostic Tests, Routine↗
PubMed2004

Development and validation of methods for assessing the quality of diagnostic accuracy studies.

OBJECTIVES: To develop a quality assessment tool which will be used in systematic reviews to assess the quality of primary studies of diagnostic accuracy. DATA SOURCES: Electronic databases including MEDLINE, EMBASE, BIOSIS and the methodological databases of both CRD and the Cochrane Collaboration. REVIEW METHODS: Three systematic reviews were conducted to provide an evidence base for the development of the quality assessment tool. A Delphi procedure was used to develop the quality assessment tool and the information provided by the reviews was incorporated into this. A panel of nine experts in the area of diagnostic accuracy studies took part in the Delphi procedure to agree on the items to be included in the tool. Panel members were also asked to provide feedback on various other items and whether they would like to see the development of additional topic and design specific items. The Delphi procedure produced the quality assessment tool, named the QUADAS tool, which consisted of 14 items. A background document was produced describing each item included in the tool and how each of the items should be scored. RESULTS: The reviews produced 28 possible items for inclusion in the quality assessment tool. It was found that the sources of bias supported by the most empirical evidence were variation by clinical and demographic subgroups, disease prevalence/severity, partial verification bias, clinical review bias and observer/instrument variation. There was also some evidence of bias for the effects of distorted selection of participants, absent or inappropriate reference standard, differential verification bias and review bias. The evidence for the effects of other sources of bias was insufficient to draw conclusions. The third review found that only one item, the avoidance of review bias, was included in more than 75% of tools. Spectrum composition, population recruitment, absent or inappropriate reference standard and verification bias were each included in 50-75% of tools. Other items were included in less than 50% of tools. The second review found that the quality assessment tool should have the potential to be discussed narratively, reported in a tabular summary, used as recommendations for future research, used to conduct sensitivity or regression analyses and used as criteria for inclusion in the review or a primary analysis. This suggested that some distinction is needed between high- and low-quality studies. Component analysis was considered the best approach to incorporate quality into systematic reviews of diagnostic studies and this was taken into consideration when developing the tool. CONCLUSIONS: This project produced an evidence-based quality assessment tool to be used in systematic reviews of diagnostic accuracy studies. Through the various stages of the project the current lack of such a tool and the need for a systematically developed validated tool were demonstrated. Further work to validate the tool continues beyond the scope of this project. The further development of the tool by the addition of design- and topic-specific criteria is proposed.

Delphi Technique↗
PubMed2003

Evaluating non-randomised intervention studies.

OBJECTIVES: To consider methods and related evidence for evaluating bias in non-randomised intervention studies. DATA SOURCES: Systematic reviews and methodological papers were identified from a search of electronic databases; handsearches of key medical journals and contact with experts working in the field. New empirical studies were conducted using data from two large randomised clinical trials. METHODS: Three systematic reviews and new empirical investigations were conducted. The reviews considered, in regard to non-randomised studies, (1) the existing evidence of bias, (2) the content of quality assessment tools, (3) the ways that study quality has been assessed and addressed. (4) The empirical investigations were conducted generating non-randomised studies from two large, multicentre randomised controlled trials (RCTs) and selectively resampling trial participants according to allocated treatment, centre and period. RESULTS: In the systematic reviews, eight studies compared results of randomised and non-randomised studies across multiple interventions using meta-epidemiological techniques. A total of 194 tools were identified that could be or had been used to assess non-randomised studies. Sixty tools covered at least five of six pre-specified internal validity domains. Fourteen tools covered three of four core items of particular importance for non-randomised studies. Six tools were thought suitable for use in systematic reviews. Of 511 systematic reviews that included non-randomised studies, only 169 (33%) assessed study quality. Sixty-nine reviews investigated the impact of quality on study results in a quantitative manner. The new empirical studies estimated the bias associated with non-random allocation and found that the bias could lead to consistent over- or underestimations of treatment effects, also the bias increased variation in results for both historical and concurrent controls, owing to haphazard differences in case-mix between groups. The biases were large enough to lead studies falsely to conclude significant findings of benefit or harm. Four strategies for case-mix adjustment were evaluated: none adequately adjusted for bias in historically and concurrently controlled studies. Logistic regression on average increased bias. Propensity score methods performed better, but were not satisfactory in most situations. Detailed investigation revealed that adequate adjustment can only be achieved in the unrealistic situation when selection depends on a single factor. CONCLUSIONS: Results of non-randomised studies sometimes, but not always, differ from results of randomised studies of the same intervention. Non-randomised studies may still give seriously misleading results when treated and control groups appear similar in key prognostic factors. Standard methods of case-mix adjustment do not guarantee removal of bias. Residual confounding may be high even when good prognostic data are available, and in some situations adjusted results may appear more biased than unadjusted results. Although many quality assessment tools exist and have been used for appraising non-randomised studies, most omit key quality domains. Healthcare policies based upon non-randomised studies or systematic reviews of non-randomised studies may need re-evaluation if the uncertainty in the true evidence base was not fully appreciated when policies were made. The inability of case-mix adjustment methods to compensate for selection bias and our inability to identify non-randomised studies that are free of selection bias indicate that non-randomised studies should only be undertaken when RCTs are infeasible or unethical. Recommendations for further research include: applying the resampling methodology in other clinical areas to ascertain whether the biases described are typical; developing or refining existing quality assessment tools for non-randomised studies; investigating how quality assessments of non-randomised studies can be incorporated into reviews and the implications of individual quality features for interpretation of a review's results; examination of the reasons for the apparent failure of case-mix adjustment methods; and further evaluation of the role of the propensity score.

Bias↗
PubMed2003

The effectiveness of diagnostic tests for the assessment of shoulder pain due to soft tissue disorders: a systematic review.

OBJECTIVES: To evaluate the evidence for the effectiveness and cost-effectiveness of the newer diagnostic imaging tests as an addition to clinical examination and patient history for the diagnosis of soft tissue shoulder disorders. DATA SOURCES: Literature was identified from several sources including general medical databases. REVIEW METHODS: Studies were identified that evaluated clinical examination, ultrasound, magnetic resonance imaging (MRI), or magnetic resonance arthrography (MRA) in patients suspected of having soft tissue shoulder disorders. Outcomes assessed were clinical impingement syndrome or rotator cuff tear (full, partial or any). Only cohort studies were included. The methodological quality of included test accuracy studies was assessed using a formal quality assessment tool for diagnostic studies and the extraction of study findings was conducted in duplicate using a pre-designed and piloted data extraction form to avoid any errors. For each test, sensitivity, specificity and positive and negative likelihood ratios with 95% confidence intervals were calculated for each study. Where possible pooled estimates of sensitivity, specificity and likelihood ratios were calculated using random effects methods. Potential sources of heterogeneity were investigated by conducting subgroup analyses. RESULTS: In the included studies, the prevalence of rotator cuff disorders was generally high, partial verification of patients was common and in many cases patients who were selected retrospectively because they had undergone the reference test. Sample sizes were generally very small. Reference tests were often inappropriate with many studies using arthrography alone, despite problems with its sensitivity. For clinical assessment, 10 cohort studies were found that examined either the accuracy of individual tests or clinical examination as a whole: individual tests were either good at ruling out rotator cuff tears when negative (high sensitivity) or at ruling in such disorders when positive (high specificity), but small sample sizes meant that there was no conclusive evidence. Ultrasound was investigated in 38 cohort studies and found to be most accurate when used for the detection of full-thickness tears; sensitivity was lower for detection of partial-thickness tears. For MRI, 29 cohort studies were included. For full-thickness tears, overall pooled sensitivities and specificities were fairly high and the studies were not statistically heterogeneous; however for the detection of partial-thickness rotator cuff tears, the pooled sensitivity estimate was much lower. The results from six MRA studies suggested that it may be very accurate for detection of full-thickness rotator cuff tears, although its performance for the detection of partial-thickness tears was less consistent. Direct evidence for the performance of one test compared with another is very limited. CONCLUSIONS: The results suggest that clinical examination by specialists can rule out the presence of a rotator cuff tear, and that either MRI or ultrasound could equally be used for detection of full-thickness rotator cuff tears, although ultrasound may be better at picking up partial tears. Ultrasound also may be more cost-effective in a specialist hospital setting for identification of full-thickness tears. Further research suggestions include the need for large, well-designed, prospective studies of the diagnosis of shoulder pain, in particular a follow-up study of patients with shoulder pain in primary care and a prospective cohort study of clinical examination, ultrasound and MRI, alone and/or in combination.

Arthrography↗
PubMed2002

A rapid and systematic review of the effectiveness of temozolomide for the treatment of recurrent malignant glioma.

A rapid and systematic review of the effectiveness and cost-effectiveness of temozolomide in the treatment of recurrent malignant glioma was commissioned by the NHS HTA Programme on behalf of NICE. The full report has been published elsewhere. This paper summarizes the results for the effectiveness of temozolomide in people with recurrent glioblastoma multiforme and anaplastic astrocytoma. The review was conducted using standard systematic review methodology involving a systematic literature search, quality assessment of included studies with systematic data extraction and data synthesis. One randomized controlled trial and four uncontrolled studies were identified for inclusion. The key results were that temozolomide may increase progression-free survival but has no significant impact on overall length of survival. The main effect from temozolomide may have been in those patients who had not received any prior chemotherapy regimens, however further randomized controlled trials are required to confirm this suggestion. Temozolomide appears to produce few serious adverse effects and may also have a positive impact on health-related quality of life. Overall the evidence-base is weak and few strong conclusions can be drawn regarding the effectiveness of temozolomide. Large, well-designed randomized controlled trails conducted in a wider patient population are needed.

Antineoplastic Agents, Alkylating↗
PubMed2001

Systematic reviews to evaluate diagnostic tests.

Diagnostic testing and screening is a critical part of the clinical process because inappropriate diagnostic strategies put patients at risk and entail a serious waste of resources. It is being increasingly recognised that absence of clear summaries of individual research studies on the repeatability, accuracy and impact of tests, which are often scattered across many different journals, is a major impediment. Just as the need to develop means to systematically review research assessing the effectiveness of treatments has been pursued over the last decade, so more recently attention has focused on how research on diagnostic tests might also be systematically reviewed. These reviews present a huge methodological challenge. This paper describes the use of a systematic approach to collation, appraisal and synthesis of information contained in the primary literature about accuracy of diagnostic strategies.

Diagnostic Techniques and Procedures↗
PubMed2001

Effectiveness and cost-effectiveness of double reading of mammograms in breast cancer screening: findings of a systematic review.

There is a lack of direct evidence on the effectiveness of double reading of breast screening mammograms within the context of national screening programmes even though about half of the countries that use mammography screening have implemented double reading. A systematic review was conducted to compare double reading with single reading of mammograms for screening accuracy, patient outcomes and costs. We searched an extensive range of electronic databases, bibliographies of studies were scanned and experts were contacted. Data extraction and quality assessment was undertaken independently by two reviewers. Estimates of the diagnostic accuracy were calculated for those studies with follow-up to identify interval cancers. Only 10 cohort studies met the inclusion criteria with reported extractable data on the effectiveness of double compared to single reading. The mix of methodologies meant that few conclusions could be drawn about the effect of double reading independent of number of views, or effects on size and type of tumours detected. Overall, double reading increases the cancer detection rate by 3-11 per 10,000 women screened and has a double impact on recall rates depending on the recall policy used. The benefit could be mainly in the detection of small cancers, and could be greatest where two readers have different strengths and weaknesses, or where readers are less experienced. Double reading can improve accuracy as compared with single reading. In particular, double reading by consensus or arbitration achieves an increase in cancer detection rate together with a reduction in the rate of women recalled for assessment. Further research should quantify the relative benefit from double reading according to recall policy and number of mammographic views, and estimate the impact on patient outcome.

Journal Article↗
PubMedDate not supplied

Cardiac rehabilitation.

Cardiac rehabilitation is provided for people following diagnosis of a range of cardiac pathologies and to aid recovery after cardiac surgery. The programmes provided cost an estimated 34 m Pounds a year. However, there is wide variation within the programmes and many do not conform to current guidance. Drawn from the NHS Centre for Reviews and Dissemination's latest Effective Health Care bulletin, this article summarises the literature on the effectiveness of cardiac rehabilitation. Its principal findings are that services do not always target all the appropriate client groups and do not always employ the most effective approaches.

Heart Diseases↗