Clare Davenport

The clinical effectiveness of different parenting programmes for children with conduct problems: a systematic review of randomised controlled trials

BackgroundConduct problems are common, disabling and costly. The prognosis for children with conduct problems is poor, with outcomes in adulthood including criminal behaviour, alcoholism, drug abuse, domestic violence, child abuse and a range of psychiatric disorders.There has been a rapid expansion of group based parent-training programmes for the treatment of children with conduct problems in a number of countries over the past 10 years. Existing reviews of parent training have methodological limitations such as inclusion of non-randomised studies, the absence of investigation for heterogeneity prior to meta-analysis or failure to report confidence intervals.The objective of the current study was to systematically review randomised controlled trials of parenting programmes for the treatment of children with conduct problems.MethodsStandard systematic review methods were followed including duplicate inclusion decisions, data extraction and quality assessment. Twenty electronic databases from the fields of medicine, psychology, social science and education were comprehensively searched for RCTs and systematic reviews to February 2006.Inclusion criteria were: randomised controlled trial; of structured, repeatable parenting programmes; for parents/carers of children up to the age of 18 with a conduct problem; and at least one measure of child behaviour. Meta-analysis and qualitative synthesis were used to summarise included studies.Results57 RCTs were included. Studies were small with an average group size of 21. Meta-analyses using both parent (SMD -0.67; 95% CI: -0.91, -0.42) and independent (SMD -0.44; 95% CI: -0.66, -0.23) reports of outcome showed significant differences favouring the intervention group. There was insufficient evidence to determine the relative effectiveness of different approaches to delivering parenting programmes.ConclusionParenting programmes are an effective treatment for children with conduct problems. The relative effectiveness of different parenting programmes requires further research.

Positron emission tomography/computerised tomography imaging in detecting and managing recurrent cervical cancer: systematic review of evidence, elicitation of subjective probabilities and economic modelling

BACKGROUND Cancer of the uterine cervix is a common cause of mortality in women. After initial treatment women may be symptom free, but the cancer may recur within a few years. It is uncertain whether it is more clinically effective to survey asymptomatic women for signs of recurrence or to await symptoms or signs before using imaging. OBJECTIVES This project compared the diagnostic accuracy of imaging using positron emission tomography/computerised tomography (PET-CT) with that of imaging using CT or magnetic resonance imaging (MRI) alone and evaluated the cost-effectiveness of adding PET-CT as an adjunct to standard practice. DATA SOURCES Standard systematic review methods were used to obtain and evaluate relevant test accuracy and effectiveness studies. Databases searched included MEDLINE, EMBASE, Science Citation Index and The Cochrane Library. All databases were searched from inception to May 2010. REVIEW METHODS Study quality was assessed using appropriately modified Quality Assessment of Diagnostic Accuracy Studies (QUADAS) criteria. Included were any studies of PET-CT, MRI or CT compared with the reference standard of histopathological findings or clinical follow-up in symptomatic women suspected of having recurrent or persistent cervical cancer and in asymptomatic women a minimum of 3 months after completion of primary treatment. Subjective elicitation of expert opinion was used to supplement diagnostic information needed for the economic evaluation. The effectiveness of treatment with chemotherapy, radiotherapy, chemoradiotherapy, radical hysterectomy and pelvic exenteration was systematically reviewed. Meta-analysis was carried out in RevMan 5.1 (The Cochrane Collaboration, The Nordic Cochrane Centre, Copenhagen, Denmark) and Stata version 11 (StataCorp LP, College Station, Texas, USA). A Markov model was developed to compare the relative cost-effectiveness using TreeAge Pro software version 2011 (TreeAge Software Inc., Evanston, IL, USA). RESULTS For the diagnostic review, a total of 7524 citations were identified, of which 12 test accuracy studies were included in the review: six studies evaluated PET-CT, two evaluated MRI, three evaluated CT and one evaluated both MRI and CT. All studies were small and the majority evaluated imaging in women in whom recurrence was suspected on the basis of symptoms. The PET-CT studies evaluated local and distant recurrence and most used methods similar to current practice, whereas five of the six CT and MRI studies evaluated local recurrence only and not all employed currently used methods. Meta-analysis of PET-CT studies gave a sensitivity of 92.2% [95% confidence interval (CI) 85.1% to 96.0%] and a specificity of 88.1% (95% CI 77.9% to 93.9%). MRI sensitivities and specificities varied between 82% and 100% and between 78% and 100%, respectively, and CT sensitivities and specificities varied between 78% and 93% and between 0% and 95%, respectively. One small study directly compared PET-CT with older imaging methods and showed more true-positives and fewer false-negatives with PET-CT. The subjective elicitation from 21 clinical experts gave test accuracy results for asymptomatic and symptomatic women and the results for symptomatic women were similar to those from the published literature. Their combined opinions also suggested that the mean elicited increase in accuracy from the addition of PET-CT to MRI and/or CT was less than the elicited minimum important difference in accuracy required to justify the routine addition of PET-CT for the investigation of women after completion of primary treatment. For the effectiveness review, a total of 24,943 citations were identified, of which 62 studies were included (chemotherapy, 19 randomised controlled trials; radiotherapy or chemoradiotherapy, 16 case series; radical hysterectomy and pelvic exenteration, 27 case series). None provided the effectiveness of cisplatin monotherapy, the most commonly used chemotherapeutic agent in the NHS, compared with supportive care in a background of other treatment such as radiotherapy in recurrent and persistent cervical cancer. The model results showed that adding PET-CT to the current treatment strategy of clinical examination, MRI and/or CT scan was significantly more costly with only a minimal increase in effectiveness, with incremental cost-effectiveness ratios for all models being > £1M per quality-adjusted life-year (QALY) and the additional cost per additional case of recurrence being in the region of £600,000. LIMITATIONS There was considerable uncertainty in many of the parameters used because of a lack of good-quality evidence in recurrent or persistent cervical cancer. The evidence on diagnostic and therapeutic impact incorporated in the economic model was poor and there was little information on surveillance of asymptomatic women. CONCLUSIONS Given the current evidence available, the addition of PET-CT to standard practice was not found to be cost-effective in the diagnosis of recurrent or persistent cervical cancer. However, although probabilistic sensitivity analysis showed that the main conclusion about cost-ineffectiveness of PET-CT was firm given the range of assumptions made, should more reliable information become available on accuracy, therapeutic impact and effectiveness, and the cost of PET-CT reduce, this conclusion may need revision. Current guidelines recommending imaging for diagnosis using expensive methods such as PET-CT need to be reconsidered in the light of the above. FUNDING The National Institute for Health Research Health Technology Assessment programme.

Do evidence-based interventions work when tested in the "real world?" A systematic review and meta-analysis of parent management training for the treatment of child disruptive behavior

Evidence-based interventions are often unavailable in everyday clinical settings. This may partly reflect practitioners’ assumptions that research evidence does not reflect “real-world” conditions. To examine this further, we systematically assessed the clinical effectiveness of parent management training (PMT) for the treatment of child disruptive behavior across different real-world practice contexts. We identified 28 relevant randomized controlled trials from a systematic search of electronic bibliographic databases and conducted a meta-analysis of child outcomes across trials. Planned subgroup analyses involved comparisons between studies grouped according to individual real-world practice criteria and total real-world practice criteria scores, reflecting the extent to which PMT was delivered by non-specialist therapists, to a clinic-referred population, in a routine setting, and as part of a routine service. Meta-analysis revealed a significant overall advantage for PMT compared with waitlist control conditions. Subgroup analyses did not demonstrate significant differences in effect size estimates according to the total number of real-world practice criteria met by studies. Moreover, no consistent relationships were found between specific practice criteria and effect size estimates. In conclusion, PMT appears to be an effective treatment for children with disruptive behavior problems. There was no clear evidence that conducting PMT in real-world practice contexts is a deterrent to achieving effective child behavior outcomes, although relative advantage to “usual care” was not directly examined and the power of the analysis was limited as a result of significant heterogeneity. More research is needed to investigate whether this finding is generalizable to other psychological interventions. Suggestions are also made for developing more differentiated criteria to assist with evaluating the specific applicability of research evidence to different care providers.

Community Programs for the Prevention of Cardiovascular Disease: A Systematic Review

In this systematic review, the authors aimed to assess the effectiveness of community programs for prevention of cardiovascular disease (CVD). They searched numerous electronic databases (CDSR, DARE, HTA, EED, and CENTRAL via the Cochrane Library, MEDLINE, MEDLINE In Process, EMBASE, CINAHL, PsycINFO, HMIC, and ASSIA) and relevant Web sites from January 1970 to mid-July 2008. Controlled studies of community programs for the primary prevention of CVD were included. Net changes in CVD risk factors were used to generate an overall index for net change in 10-year CVD risk. The authors identified 36 relevant community programs that took place between 1970 and 2008. These programs were multifaceted interventions employing combinations of media, screening, and counseling activities and environmental changes and were primarily evaluated using controlled before-after studies. In 7 studies, investigators reported changes in CVD/total mortality rates, and in 5 they reported net changes. In all cases, these net changes were positive but were largely nonsignificant. In 22 studies, investigators reported changes in physiologic CVD risk factors, and there was a positive trend in the calculated CVD risk score. The average net reduction in 10-year CVD risk was 0.65%. Community programs for CVD prevention appear to have generally achieved favorable changes in overall CVD risk and, with adaptation to current circumstances, deserve continued consideration as possible approaches to preventing CVD.

A capture-recapture analysis demonstrated that randomized controlled trials evaluating the impact of diagnostic tests on patient outcomes are rare

OBJECTIVE To estimate the number of randomized controlled trials (RCTs) published annually that evaluate the impact of diagnostic tests on patient outcomes to gauge the extent of available randomized evidence assessing the effectiveness of diagnostic tests. STUDY DESIGN AND SETTING Relevant RCTs published in 2004-2007 were identified from electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL). Two search strategies were developed, one using diagnostic methodological terms and one using test names. Potentially relevant RCTs were identified by screening titles and abstracts. Final inclusion decisions were based on full-text review. A random 10% sample of all citations was independently screened by a second reviewer. Capture-recapture methodology was used to estimate the number of relevant RCTs missed by both searches. RESULTS One hundred thirty-five relevant RCTs were identified from the 23,888 records retrieved. Interobserver agreement was substantial. Capture-recapture methodology estimated that 148 (95% confidence interval: 140, 160) relevant RCTs were published in the 4-year period, an average of only 37 publications per year. CONCLUSION RCTs of diagnostic tests that evaluate patient outcomes are rare. Consequently recommendations on the use of diagnostic tests can rarely be made on the basis of randomized comparisons, lower grade evidence frequently being the best available.

Applying Grading of Recommendations Assessment, Development and Evaluation (GRADE) to diagnostic tests was challenging but doable

OBJECTIVES The Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group developed an approach to assess the quality of evidence of diagnostic tests. Its use in Cochrane diagnostic test accuracy reviews is new. We applied this approach to three Cochrane reviews with the aim of better understanding the application of the GRADE criteria to such reviews. STUDY DESIGN AND SETTING We selected reviews to achieve clinical and methodological diversities. At least three assessors independently assessed each review according to the GRADE criteria of risk of bias, indirectness, imprecision, inconsistency, and publication bias. Two teleconferences were held to share experiences. RESULTS For the interpretation of the GRADE criteria, it made a difference whether assessors looked at the evidence from a patient-important outcome perspective or from a test accuracy standpoint. GRADE criteria such as inconsistency, imprecision, and publication bias were challenging to apply as was the assessment of comparative test accuracy reviews. CONCLUSION The perspective from which evidence is graded can influence judgments about quality. Guidance on application of GRADE to comparative test reviews and on the GRADE criteria of inconsistency, imprecision, and publication bias will facilitate the operationalization of GRADE for diagnostics.

MANAGEMENT OF ENDOCRINE DISEASE: Imaging for the diagnosis of malignancy in incidentally discovered adrenal masses: a systematic review and meta-analysis.

Objective Adrenal masses are incidentally discovered in 5% of CT scans. In 2013/2014, 81 million CT examinations were undertaken in the USA and 5 million in the UK. However, uncertainty remains around the optimal imaging approach for diagnosing malignancy. We aimed to review the evidence on the accuracy of imaging tests for differentiating malignant from benign adrenal masses. Design A systematic review and meta-analysis was conducted. Methods We searched MEDLINE, EMBASE, Cochrane CENTRAL Register of Controlled Trials, Science Citation Index, Conference Proceedings Citation Index, and ZETOC (January 1990 to August 2015). We included studies evaluating the accuracy of CT, MRI, or 18F-fluoro-deoxyglucose (FDG)-PET compared with an adequate histological or imaging-based follow-up reference standard. Results We identified 37 studies suitable for inclusion, after screening 5469 references and 525 full-text articles. Studies evaluated the accuracy of CT (n=16), MRI (n=15), and FDG-PET (n=9) and were generally small and at high or unclear risk of bias. Only 19 studies were eligible for meta-analysis. Limited data suggest that CT density >10HU has high sensitivity for detection of adrenal malignancy in participants with no prior indication for adrenal imaging, that is, masses with ≤10HU are unlikely to be malignant. All other estimates of test performance are based on too small numbers. Conclusions Despite their widespread use in routine assessment, there is insufficient evidence for the diagnostic value of individual imaging tests in distinguishing benign from malignant adrenal masses. Future research is urgently needed and should include prospective test validation studies for imaging and novel diagnostic approaches alongside detailed health economics analysis.

How well do health professionals interpret diagnostic information? A systematic review

Objective To evaluate whether clinicians differ in how they evaluate and interpret diagnostic test information. Design Systematic review. Data sources MEDLINE, EMBASE and PsycINFO from inception to September 2013; bibliographies of retrieved studies, experts and citation search of key included studies. Eligibility criteria for selecting studies Primary studies that provided information on the accuracy of any diagnostic test (eg, sensitivity, specificity, likelihood ratios) to health professionals and that reported outcomes relating to their understanding of information on or implications of test accuracy. Results We included 24 studies. 6 assessed ability to define accuracy metrics: health professionals were less likely to identify the correct definition of likelihood ratios than of sensitivity and specificity. –25 studies assessed Bayesian reasoning. Most assessed the influence of a positive test result on the probability of disease: they generally found health professionals’ estimation of post-test probability to be poor, with a tendency to overestimation. 3 studies found that approaches based on likelihood ratios resulted in more accurate estimates of post-test probability than approaches based on estimates of sensitivity and specificity alone, while 3 found less accurate estimates. 5 studies found that presenting natural frequencies rather than probabilities improved post-test probability estimation and speed of calculations. Conclusions Commonly used measures of test accuracy are poorly understood by health professionals. Reporting test accuracy using natural frequencies and visual aids may facilitate improved understanding and better estimation of the post-test probability of disease.

Evaluating PET-CT in the detection and management of recurrent cervical cancer: Systematic reviews of diagnostic accuracy and subjective elicitation

Positron emission tomography–computed tomography (PET‐CT) is recommended to triage women for exenterative surgery and surveillance after treatment for advanced cervical cancer.

Evaluating PET-CT in routine surveillance and follow-up after treatment for cervical cancer: a cost-effectiveness analysis

To undertake a cost‐effectiveness analysis that compares positron emission tomography – computed tomography (PET‐CT) imaging plus standard practice with standard practice alone in the diagnosis of recurrent or persistent cervical cancer during routine surveillance and follow‐up of women who have previously been diagnosed and treated.