The Cochrane Handbook for Systematic Reviews of Interventions is the official document that describes in detail the process of preparing and maintaining Cochrane systematic reviews on the effects of healthcare interventions.

/pdf/cochrane-handbook-for-systematic-reviews-of-interventions-1xbdy6uvru.pdf

Cochrane Handbook for Systematic Reviews of Interventions

Overwhelming evidence shows the quality of reporting of randomised controlled trials (RCTs) is not optimal. Without transparent reporting, readers cannot judge the reliability and validity of trial findings nor extract information for systematic reviews. Recent methodological analyses indicate that inadequate reporting and design are associated with biased estimates of treatment effects. Such systematic error is seriously damaging to RCTs, which are considered the gold standard for evaluating interventions because of their ability to minimise or avoid bias. A group of scientists and editors developed the CONSORT (Consolidated Standards of Reporting Trials) statement to improve the quality of reporting of RCTs. It was first published in 1996 and updated in 2001. The statement consists of a checklist and flow diagram that authors can use for reporting an RCT. Many leading medical journals and major international editorial groups have endorsed the CONSORT statement. The statement facilitates critical appraisal and interpretation of RCTs. During the 2001 CONSORT revision, it became clear that explanation and elaboration of the principles underlying the CONSORT statement would help investigators and others to write or appraise trial reports. A CONSORT explanation and elaboration article was published in 2001 alongside the 2001 version of the CONSORT statement. After an expert meeting in January 2007, the CONSORT statement has been further revised and is published as the CONSORT 2010 Statement. This update improves the wording and clarity of the previous checklist and incorporates recommendations related to topics that have only recently received recognition, such as selective outcome reporting bias. This explanatory and elaboration document-intended to enhance the use, understanding, and dissemination of the CONSORT statement-has also been extensively revised. It presents the meaning and rationale for each new and updated checklist item providing examples of good reporting and, where possible, references to relevant empirical studies. Several examples of flow diagrams are included. The CONSORT 2010 Statement, this revised explanatory and elaboration document, and the associated website (www.consort-statement.org) should be helpful resources to improve reporting of randomised trials.

https://www.bmj.com/content/bmj/340/bmj.c869.full.pdf

CONSORT 2010 Explanation and Elaboration: updated guidelines for reporting parallel group randomised trials

There is increasing concern that most current published research findings are false. The probability that a research claim is true may depend on study power and bias, the number of other studies on the same question, and, importantly, the ratio of true to no relationships among the relationships probed in each scientific field. In this framework, a research finding is less likely to be true when the studies conducted in a field are smaller; when effect sizes are smaller; when there is a greater number and lesser pre-selection of tested relationships; where there is greater flexibility in designs, definitions, outcomes, and analytical modes; when there is greater financial and other interest and prejudice; and when more teams are involved in a scientific field in chase of statistical significance. Simulations show that for most study designs and settings, it is more likely for a research claim to be false than true. Moreover, for many current scientific fields, claimed research findings may often be simply accurate measures of the prevailing bias. In this essay, I discuss the implications of these problems for the conduct and interpretation of research.

Why Most Published Research Findings Are False

Summary There is increasing concern that most current published research fi ndings are false. The probability that a research claim is true may depend on study power and bias, the number of other studies on the same question, and, importantly, the ratio of true to no relationships among the relationships probed in each scientifi c fi eld. In this framework, a research fi nding is less likely to be true when the studies conducted in a fi eld are smaller; when effect sizes are smaller; when there is a greater number and lesser preselection of tested relationships; where there is greater fl exibility in designs, defi nitions, outcomes, and analytical modes; when there is greater fi nancial and other interest and prejudice; and when more teams are involved in a scientifi c fi eld in chase of statistical signifi cance. Simulations show that for most study designs and settings, it is more likely for a research claim to be false than true. Moreover, for many current scientifi c fi elds, claimed research fi ndings may often be simply accurate measures of the prevailing bias. In this essay, I discuss the implications of these problems for the conduct and interpretation of research. It can be proven that most claimed research fi ndings are false.

/pdf/why-most-published-research-findings-are-false-32jor6sj5q.pdf

An earlier version (version 5.0.2, 2008) of the Handbook is also published by John Wiley & Sons, Ltd under “The Cochrane Book Series” Imprint, as Higgins JPT, Green S (editors), Cochrane Handbook for Systematic Reviews of Interventions (ISBN 978-0470057964) by John Wiley & Sons Ltd, The Atrium, Southern Gate, Chichester, West Sussex PO19 8SQ, England, Telephone (+44) 1243 779777; Email (for orders and customer service enquiries): cs-books@wiley.co.uk. Visit their Home Page on www.wiley.com.

Chapter 8: Assessing risk of bias in included studies

Context Duration of untreated psychosis (DUP) is the time from manifestation of the first psychotic symptom to initiation of adequate treatment. It has been postulated that a longer DUP leads to a poorer prognosis. If so, outcome might be improved through earlier detection and treatment. Objectives To establish whether DUP is associated with prognosis and to determine whether any association is explained by confounding with premorbid adjustment. Data Sources The CINAHL (Cumulative Index to Nursing and Allied Health), EMBASE, MEDLINE, and PsychLIT databases were searched from their inception dates to May 2004. Study Selection Eligible studies reported the relationship between DUP and outcome in prospective cohorts recruited during their first episode of psychosis. Twenty-six eligible studies involving 4490 participants were identified from 11 458 abstracts, each screened by 2 reviewers. Data Extraction Data were extracted independently and were checked by double entry. Sensitivity analyses were conducted excluding studies that had follow-up rates of less than 80%, included affective psychoses, or did not use a standardized assessment of DUP. Data Synthesis Independent meta-analyses were conducted of correlational data and of data derived from comparisons of long and short DUP groups. Most data were correlational, and these showed a significant association between DUP and several outcomes at 6 and 12 months (including total symptoms, depression/anxiety, negative symptoms, overall functioning, positive symptoms, and social functioning). Long vs short DUP data showed an association between longer DUP and worse outcome at 6 months in terms of total symptoms, overall functioning, positive symptoms, and quality of life. Patients with a long DUP were significantly less likely to achieve remission. The observed association between DUP and outcome was not explained by premorbid adjustment. Conclusions There is convincing evidence of a modest association between DUP and outcome, which supports the case for clinical trials that examine the effect of reducing DUP.

/pdf/association-between-duration-of-untreated-psychosis-and-3d33a68pa1.pdf

Association Between Duration of Untreated Psychosis and Outcome in Cohorts of First-Episode Patients: A Systematic Review

Background A recent review suggested an association between using unpublished scales in clinical trials and finding significant results.

Aims To determine whether such an association existed in schizophrenia trials.

Method Three hundred trials were randomly selected from the Cochrane Schizophrenia Group's Register. All comparisons between treatment groups and control groups using rating scales were identified. The publication status of each scale was determined and claims of a significant treatment effect were recorded.

Results Trials were more likely to report that a treatment was superior to control when an unpublished scale was used to make the comparison (relative risk 1.37 (95% C11.12-1.68)). This effect increased when a ‘ gold-standard’ definition of treatment superiority was applied (RR 1.94(95%C11.35-2.79)). In non-pharmacological trials, one-third of ‘ gold-standard’ claims of treatment superiority would not have been made if published scales had been used.

Conclusions Unpublished scales are a source of bias in schizophrenia trials.

/pdf/unpublished-rating-scales-a-major-source-of-bias-in-46xbbw3wff.pdf

Unpublished rating scales: a major source of bias in randomised controlled trials of treatments for schizophrenia.

Objective: To determine the most effective way of helping people with severe mental illness to obtain competitive employment—that is, a job paid at the market rate, and for which anyone can apply. Design: Systematic review. Participants: Eligible studies were randomised controlled trials comparing prevocational training or supported employment (for people with severe mental illness) with each other or with standard community care. Outcome measures: The primary outcome was number of subjects in competitive employment. Secondary outcomes were other employment outcomes, clinical outcomes, and costs. Results: Eleven trials met the inclusion criteria. Five (1204 subjects) compared prevocational training with standard community care, one (256 subjects) compared supported employment with standard community care, and five (484 subjects) compared supported employment with prevocational training. Subjects in supported employment were more likely to be in competitive employment than those who received prevocational training at 4, 6, 9, 12, 15, and 18 months (for example, 34% v 12% at 12 months; number needed to treat 4.45, 95% confidence interval 3.37 to 6.59). This effect was still present, although at a reduced level, after a sensitivity analysis that retained only the highest quality trials (31% v 12%; 5.3, 3.6 to 10.4). People in supported employment earned more and worked more hours per month than those who had had prevocational training. Conclusion: Supported employment is more effective than prevocational training at helping people with severe mental illness obtain competitive employment.

https://www.bmj.com/content/bmj/322/7280/204.full.pdf

Helping people with severe mental illness to obtain work: systematic review

Background
Assertive Community Treatment (ACT) was developed in the early 1970s as a response to the closing down of psychiatric hospitals. ACT is a team-based approach aiming at keeping ill people in contact with services, reducing hospital admissions and improving outcome, especially social functioning and quality of life.

Objectives
To determine the effectiveness of Assertive Community Treatment (ACT) as an alternative to i. standard community care, ii. traditional hospital-based rehabilitation, and iii. case management. For each of the three comparisons the main outcome indices were i. remaining in contact with the psychiatric services, ii. extent of psychiatric hospital admissions, iii. clinical and social outcome and iv. costs.

Search strategy
Electronic searches of CINAHL (1982-1997), the Cochrane Schizophrenia Group's Register of trials (1997), EMBASE (1980-1997), MEDLINE (1966-1997), PsycLIT (1974-1997) and SCISEARCH (1997) were undertaken. References of all identified studies were searched for further trial citations.

Selection criteria
The inclusion criteria were that studies should i. be randomised controlled trials, ii. have compared ACT to standard community care, hospital-based rehabilitation, or case management and iii. have been carried out on people with severe mental disorder the majority of whom were aged from 18 to 65. Studies of ACT were defined as those in which the investigators described the intervention as "Assertive Community Treatment" or one of its synonyms. Studies of ACT as an alternative to hospital admission, hospital diversion programmes, for those in crisis, were excluded. The reliability of the inclusion criteria were evaluated.

Data collection and analysis
Three types of outcome data were available: i. categorical data, ii. numerical data based on counts of real life events (count data) and iii. numerical data collected by standardised instruments (scale data). Categorical data were extracted twice and then cross-checked. Peto Odds Ratios and the number needed to treat (NNT) were calculated. Numerical count data were extracted twice and cross-checked. Count data could not be combined across studies for technical reasons (the data were skewed) but all relevant observations based on count data were reported in the review. Numerical scale data were subject to a quality assessment. The validity of the quality assessment was itself assessed. Numerical scale data of suitable quality were combined using the standardised mean difference statistic where possible, otherwise the data were reported in the text or 'Other data tables' of the review.

Main results
ACT versus standard community care 
Those receiving ACT were more likely to remain in contact with services than people receiving standard community care (OR 0.51, 99%CI 0.37-0.70). People allocated to ACT were less likely to be admitted to hospital than those receiving standard community care (OR 0.59, 99%CI 0.41-0.85) and spent less time in hospital. In terms of clinical and social outcome, significant and robust differences between ACT and standard community care were found on i. accommodation status, ii. employment and iii. patient satisfaction. There were no differences between ACT and control treatments on mental state or social functioning. ACT invariably reduced the cost of hospital care, but did not have a clear cut advantage over standard care when other costs were taken into account.

ACT versus hospital-based rehabilitation services 
Those receiving ACT were no more likely to remain in contact with services than those receiving hospital-based rehabilitation, but confidence intervals for the odds ratio were wide. People getting ACT were significantly less likely to be admitted to hospital than those receiving hospital-based rehabilitation (OR 0.2, 99%CI 0.09-0.46) and spent less time in hospital. Those allocated to ACT were significantly more likely to be living independently (OR (for not living independently) 0.19, 99%CI 0.06-0.54), but there were no other significant and robust differences in clinical or social outcome. There was insufficient data on costs to permit comparison.

ACT versus case management 
There were no data on numbers remaining in contact with the psychiatric services or on numbers admitted to hospital. People allocated to ACT consistently spent fewer days in hospital than those given case management. There was insufficient data to permit robust comparisons of clinical or social outcome. The cost of hospital care was consistently less for those allocated to ACT, but ACT did not have a clear cut advantage over case management when other costs were taken into account.

Authors' conclusions
ACT is a clinically effective approach to managing the care of severely mentally ill people in the community. ACT, if correctly targeted on high users of in-patient care, can substantially reduce the costs of hospital care whilst improving outcome and patient satisfaction. Policy makers, clinicians, and consumers should support the setting up of ACT teams.

Assertive community treatment for people with severe mental disorders

Background Proponents of early intervention have argued that outcome might be improved if more therapeutic effort were focused on the early stages of schizophrenia. Early intervention in schizophrenia has two elements that are distinct from standard care: early detection and phase-specific treatment. Both elements may be offered in addition to standard care, or may be provided by a specialised early intervention team. Early intervention is now well established as a therapeutic approach in America, Europe and Australasia, but it is unclear how far early detection, phase-specific treatments, and the use of early intervention teams are underpinned by evidence of effectiveness. Objectives This review aims to evaluate the effects of: i. early detection and treatment of people with prodromal symptoms; ii. the use of early intervention teams for people in their first episode of psychosis; and iii. phase-specific treatments for people in their first episode of psychosis. Search strategy We searched CINAHL (1982-2002), The Cochrane Controlled Trials Register (November 2001), The Cochrane Schizophrenia Group Register (July 2003), EMBASE (1980-2002), MEDLINE (1966-2002), PsycINFO (1967-2002), reference lists and contacted the European First Episode Network (2003). Selection criteria Randomised controlled trials designed to prevent progression to psychosis in people showing prodromal symptoms, or improve outcome for people with first episode psychosis. Eligible interventions, alone and in combination, included early detection, phase-specific treatments, and care from specialised early intervention teams. Non-randomised trials would only have been included if they had been studies of the effects of early detection strategies in reducing the duration of untreated psychosis (since this issue cannot be addressed by simple randomisation). Data collection and analysis Data were extracted independently by two reviewers and cross-checked. Relative risks (RR) and 95% confidence intervals (CI) were calculated for dichotomous data. Weighted mean differences (WMD) were calculated for continuous data. Main results In theory, seventeen different comparisons are possible, but the review only identified three studies that met inclusion criteria. One small trial (n=59) was concerned with a phase-specific intervention (low dose risperidone and cognitive behavioural therapy) for people with prodromal symptoms. This group were significantly less likely to develop psychosis at 6 month follow up than people who only received care from a specialised team which did not involve phase-specific treatment (n=59, 1 RCT, RR 0.27 CI 0.08 to 0.89, NNT 4 CI 2 to 20). This effect was not significant at 12 month follow up (n=59, 1 RCT, RR 0.54 CI 0.23 to 1.30). Another trial found that people in their first episode receiving a phase-specific intervention (family therapy) plus out patient care did have reduced admission rates care compared with those who received only outpatient care (n=83, 1 RCT, RR 0.28 CI 0.13 to 0.62, NNT 3 CI 2 to 6). The applicability of this finding was, however, questionable.Finally, one last study (n=76), comparing phase-specific intervention (family therapy) plus specialised team with specialised team for people in their first episode of schizophrenia found no difference between intervention and control groups at 12 months for the outcome of relapse but confidence intervals were wide (n=76, RR 1.06 CI 0.31 to 3.65). Reviewers' conclusions We identified insufficient trials to draw any definitive conclusions, although five ongoing trials should report shortly. The substantial international interest in early intervention offers an opportunity to make major positive changes in psychiatric practice, but this opportunity may be missed without a concerted international programme of research to address key unanswered questions.

/pdf/early-intervention-for-psychosis-4ph3b264l1.pdf

Max Marshall

Papers

Association Between Duration of Untreated Psychosis and Outcome in Cohorts of First-Episode Patients: A Systematic Review

Unpublished rating scales: a major source of bias in randomised controlled trials of treatments for schizophrenia.

Helping people with severe mental illness to obtain work: systematic review

Assertive community treatment for people with severe mental disorders

Early Intervention for Psychosis