Thinking territory historically.

BACKGROUND: While the randomised controlled trial (RCT) is generally regarded as the design of choice for assessing the effects of health care, within the social sciences there is considerable debate about the relative suitability of RCTs and non-randomised studies (NRSs) for evaluating public policy interventions. // OBJECTIVES: To determine whether RCTs lead to the same effect size and variance as NRSs of similar policy interventions; and whether these findings can be explained by other factors associated with the interventions or their evaluation. // METHODS: Analyses of methodological studies, empirical reviews, and individual health and social services studies investigated the relationship between randomisation and effect size of policy interventions by: 1) Comparing controlled trials that are identical in all respects other than the use of randomisation by 'breaking' the randomisation in a trial to create non-randomised trials (re-sampling studies). 2) Comparing randomised and non-randomised arms of controlled trials mounted simultaneously in the field (replication studies). 3) Comparing similar controlled trials drawn from systematic reviews that include both randomised and non-randomised studies (structured narrative reviews and sensitivity analyses within meta-analyses). 4) Investigating associations between randomisation and effect size using a pool of more diverse RCTs and NRSs within broadly similar areas (meta-epidemiology). // RESULTS: Prior methodological reviews and meta-analyses of existing reviews comparing effects from RCTs and nRCTs suggested that effect sizes from RCTs and nRCTs may indeed differ in some circumstances and that these differences may well be associated with factors confounded with design. Re-sampling studies offer no evidence that the absence of randomisation directly influences the effect size of policy interventions in a systematic way. No consistent explanations were found for randomisation being associated with changes in effect sizes of policy interventions in field trials

The Moses–Littenberg meta-analytical method generates systematic differences in test accuracy compared to hierarchical meta-analytical models

AbstractObjectiveTo compare meta-analyses of diagnostic test accuracy using the Moses–Littenberg summary receiver operating characteristic (SROC) approach with those of the hierarchical SROC (HSROC) model.Study Design and SettingTwenty-six data sets from existing test accuracy systematic reviews were reanalyzed with the Moses–Littenberg model, using equal weighting (“E-ML”) and weighting by the inverse variance of the log DOR (“W-ML”), and with the HSROC model. The diagnostic odds ratios (DORs) were estimated and covariates added to both models to estimate relative DORs (RDORs) between subgroups. Models were compared by calculating the ratio of DORs, the ratio of RDORs, and P-values for detecting asymmetry and effects of covariates on DOR.ResultsCompared to the HSROC model, the Moses–Littenberg model DOR estimates were a median of 22% (“E-ML”) and 47% (“W-ML”) lower at Q*, and 7% and 42% lower at the central point in the data. Instances of the ML models giving estimates higher than the HSROC model also occurred. Investigations of heterogeneity also differed; the Moses–Littenberg models on average estimating smaller differences in RDOR.ConclusionsMoses–Littenberg meta-analyses can generate lower estimates of test accuracy, and smaller differences in accuracy, compared to mathematically superior hierarchical models. This has implications for the usefulness of meta-analyses using this approach. We recommend meta-analysis of diagnostic test accuracy studies to be conducted using available hierarchical model–based approaches

AN AUTOREGRESSION MODEL FOR A PAIRED WATERSHED COMPARISON

Analysis of water quality data from a paired watershed design is needed to determine if a best fertilizer management practice reduces a specific water quality variable compared to a conventional fertilizer management practice. This study examines an existing recommended method of analysis for paired watershed designs, simple analysis of covariance (ANCOVA) on time aggregated data, then offers two autoregression analyses (AR) as alternatives. The first approach models the sequence of paired differences and estimates its 95% confidence band. The second approach develops individual watershed AR models then examines the joint 95% confidence interval about the predicted difference. A reliability analysis on the water quality data reveals that the data for the controlled watershed, i.e., the covariate, has a sizable measurement error, a factor that is not considered in the usual ANCOVA model. The AR methods avoid the measurement error and other inherent problems with the published recommended method. Graphically both AR analyses are similar and reveal three distinct trend phases: a period of continued similarity; a period of transition; and a period of sustained change. The model for the sequence of paired differences is the easier one of the two AR methods to use and interpret because its trend model of splined linear segments readily defines each response phase. Hence, we recommend it over the given alternatives. It offers water resources researchers an effective and readily adoptable analysis option

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

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

Ambulatory chemotherapy : past, present and future

Ambulatory chemotherapy allows the delivery of short and extended chemotherapy infusions through a portable pump from the comfort of patients’ homes. It is essential to offer it for suitable candidates to ensure both their safety and the success of the treatment session. This requires a delicate balance between clinical assessment and patient acceptance. The two main components of this treatment modality are the pump and the access device. There are several pump designs and mechanisms on the market, with the latest being the portable disposable elastomeric one. Clinicians along with a multidisciplinary medical team often decide upon the type of access device; patients are also involved whenever shared decision making is practiced. Despite some reports of pump programming errors or malfunctions, research is underway to find innovative solutions to support its use

Test-treatment RCTs are susceptible to bias:a review of the methodological quality of randomized trials that evaluate diagnostic tests

Abstract Background There is a growing recognition for the need to expand our evidence base for the clinical effectiveness of diagnostic tests. Many international bodies are calling for diagnostic randomized controlled trials to provide the most rigorous evidence of impact to patient health. Although these so-called test-treatment RCTs are very challenging to undertake due to their methodological complexity, they have not been subjected to a systematic appraisal of their methodological quality. The extent to which these trials may be producing biased results therefore remains unknown. We set out to address this issue by conducting a methodological review of published test-treatment trials to determine how often they implement adequate methods to limit bias and safeguard the validity of results. Methods We ascertained all test-treatment RCTs published 2004–2007, indexed in CENTRAL, including RCTs which randomized patients to diagnostic tests and measured patient outcomes after treatment. Tests used for screening, monitoring or prognosis were excluded. We assessed adequacy of sequence generation, allocation concealment and intention-to-treat, appropriateness of primary analyses, blinding and reporting of power calculations, and extracted study characteristics including the primary outcome. Results One hundred three trials compared 105 control with 119 experimental interventions, and reported 150 primary outcomes. Randomization and allocation concealment were adequate in 57 and 37% of trials. Blinding was uncommon (patients 5%, clinicians 4%, outcome assessors 21%), as was an adequate intention-to-treat analysis (29%). Overall 101 of 103 trials (98%) were at risk of bias, as judged using standard Cochrane criteria. Conclusion Test-treatment trials are particularly susceptible to attrition and inadequate primary analyses, lack of blinding and under-powering. These weaknesses pose much greater methodological and practical challenges to conducting reliable RCT evaluations of test-treatment strategies than standard treatment interventions. We suggest a cautious approach that first examines whether a test-treatment intervention can accommodate the methodological safeguards necessary to minimize bias, and highlight that test-treatment RCTs require different methods to ensure reliability than standard treatment trials. Please see the companion paper to this article: http://bmcmedresmethodol.biomedcentral.com/articles/10.1186/s12874-016-0286-0

Guidance for the design and reporting of studies evaluating the clinical performance of tests for present or past SARS-CoV-2 infection

Testing for SARS-CoV-2 infection is key in managing the current pandemic. More than 1700 preprints and peer reviewed journal articles evaluating tests for SARS-CoV-2 infection have been published as of January 2021. However, evaluations of these studies have identified many methodological issues, leading to a high risk of bias and difficulties applying the results in practice. Better guidance is urgently needed on the conduct and interpretation of these studies. This article outlines the principles for defining the intended purpose of the test; study population selection; reference standard, test timing; and other critical considerations for the design, reporting, and interpretation of diagnostic accuracy studies. The implementation and accuracy of SARS-CoV-2 tests have major implications for individuals and communities, balancing the potential consequences of continued infection against the need for public health measures, such as the restriction of movements and social activities. Decision making in the current pandemic requires a clear understanding of the clinical performance and limitations of testing. This article provides guidance to assist researchers design robust diagnostic accuracy studies, assist publishers and peer reviewers to assess such studies, and support clinicians and policy makers in their evaluation of the evidence on SARS-CoV-2 testing for clinical and public health decisions. The guidance aims to ensure that studies evaluating the diagnostic accuracy of SARS-CoV-2 tests are conducted as rigorously as possible, in an efficient and timely way

Medical Selfies: Emotional Impacts and Practical Challenges

Medical images taken with mobile phones by patients, i.e. medical selfies, allow screening, monitoring and diagnosis of skin lesions. While mobile teledermatology can provide good diagnostic accuracy for skin tumours, there is little research about emotional and physical aspects when taking medical selfies of body parts. We conducted a survey with 100 participants and a qualitative study with twelve participants, in which they took images of eight body parts including intimate areas. Participants had difficulties taking medical selfies of their shoulder blades and buttocks. For the genitals, they prefer to visit a doctor rather than sending images. Taking the images triggered privacy concerns, memories of past experiences with body parts and raised awareness of the bodily medical state. We present recommendations for the design of mobile apps to address the usability and emotional impacts of taking medical selfies

Electronic and animal noses for detecting SARS-CoV-2 infection (Protocol)

This is a protocol for a Cochrane Review (diagnostic). The objectives are as follows: 1. To assess the diagnostic test accuracy of eNoses to screen for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in public places, such as airports. 2. To assess the diagnostic test accuracy of sniffer animals, and more specifically dogs, to screen for SARS-CoV-2 infection in public places, such as airports. 3. To assess the diagnostic test accuracy of eNoses for SARS-CoV-2 infection or COVID-19 in symptomatic people presenting in the community, or in secondary care. 4. To assess the diagnostic test accuracy of sniffer animals, and more specifically dogs, for SARS-CoV-2 infection or COVID-19 in symptomatic people presenting in the community, or in secondary care