David Moher and colleagues introduce PRISMA, an update of the QUOROM guidelines for reporting systematic reviews and meta-analyses

/pdf/preferred-reporting-items-for-systematic-reviews-and-meta-3k0wa2mp7o.pdf

Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement

Systematic reviews and meta-analyses have become increasingly important in health care. Clinicians read them to keep up to date with their field,1,2 and they are often used as a starting point for developing clinical practice guidelines. Granting agencies may require a systematic review to ensure there is justification for further research,3 and some health care journals are moving in this direction.4 As with all research, the value of a systematic review depends on what was done, what was found, and the clarity of reporting. As with other publications, the reporting quality of systematic reviews varies, limiting readers' ability to assess the strengths and weaknesses of those reviews.

Several early studies evaluated the quality of review reports. In 1987, Mulrow examined 50 review articles published in 4 leading medical journals in 1985 and 1986 and found that none met all 8 explicit scientific criteria, such as a quality assessment of included studies.5 In 1987, Sacks and colleagues6 evaluated the adequacy of reporting of 83 meta-analyses on 23 characteristics in 6 domains. Reporting was generally poor; between 1 and 14 characteristics were adequately reported (mean = 7.7; standard deviation = 2.7). A 1996 update of this study found little improvement.7

In 1996, to address the suboptimal reporting of meta-analyses, an international group developed a guidance called the QUOROM Statement (QUality Of Reporting Of Meta-analyses), which focused on the reporting of meta-analyses of randomized controlled trials.8 In this article, we summarize a revision of these guidelines, renamed PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses), which have been updated to address several conceptual and practical advances in the science of systematic reviews (Box 1).



Box 1

Conceptual issues in the evolution from QUOROM to PRISMA

Preferred reporting items for systematic reviews and meta-analyses: the PRISMA Statement.

Objective: Funnel plots (plots of effect estimates against sample size) may be useful to detect bias in meta-analyses that were later contradicted by large trials. We examined whether a simple test of asymmetry of funnel plots predicts discordance of results when meta-analyses are compared to large trials, and we assessed the prevalence of bias in published meta-analyses. Design: Medline search to identify pairs consisting of a meta-analysis and a single large trial (concordance of results was assumed if effects were in the same direction and the meta-analytic estimate was within 30% of the trial); analysis of funnel plots from 37 meta-analyses identified from a hand search of four leading general medicine journals 1993-6 and 38 meta-analyses from the second 1996 issue of the Cochrane Database of Systematic Reviews . Main outcome measure: Degree of funnel plot asymmetry as measured by the intercept from regression of standard normal deviates against precision. Results: In the eight pairs of meta-analysis and large trial that were identified (five from cardiovascular medicine, one from diabetic medicine, one from geriatric medicine, one from perinatal medicine) there were four concordant and four discordant pairs. In all cases discordance was due to meta-analyses showing larger effects. Funnel plot asymmetry was present in three out of four discordant pairs but in none of concordant pairs. In 14 (38%) journal meta-analyses and 5 (13%) Cochrane reviews, funnel plot asymmetry indicated that there was bias. Conclusions: A simple analysis of funnel plots provides a useful test for the likely presence of bias in meta-analyses, but as the capacity to detect bias will be limited when meta-analyses are based on a limited number of small trials the results from such analyses should be treated with considerable caution. Key messages Systematic reviews of randomised trials are the best strategy for appraising evidence; however, the findings of some meta-analyses were later contradicted by large trials Funnel plots, plots of the trials9 effect estimates against sample size, are skewed and asymmetrical in the presence of publication bias and other biases Funnel plot asymmetry, measured by regression analysis, predicts discordance of results when meta-analyses are compared with single large trials Funnel plot asymmetry was found in 38% of meta-analyses published in leading general medicine journals and in 13% of reviews from the Cochrane Database of Systematic Reviews Critical examination of systematic reviews for publication and related biases should be considered a routine procedure

/pdf/bias-in-meta-analysis-detected-by-a-simple-graphical-test-5erh428s5c.pdf

Bias in meta-analysis detected by a simple, graphical test

Systematic review and meta-analysis

Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement

Overdiagnosis in cancer screening is the detection of cancer lesions that would otherwise not have been detected. It is arguably the most important harm. We quantified overdiagnosis in the Danish mammography screening programme, which is uniquely suited for this purpose, as only 20% of the Danish population has been offered organised mammography screening over a long time-period. We collected incidence rates of carcinoma in situ and invasive breast cancer in areas with and without screening over 13 years with screening (1991-2003), and 20 years before its introduction (1971-1990). We explored the incidence increase comparing unadjusted incidence rates and used Poisson regression analysis to compensate for the background incidence trend, variation in age distribution and geographical variation in incidence. For the screened age group, 50 to 69 years, we found an overdiagnosis of 35% when we compared unadjusted incidence rates for the screened and non-screened areas, but after compensating for a small decline in incidence in older, previously screened women. Our adjusted Poisson regression analysis indicated a relative risk of 1.40 (95% CI: 1.35-1.45) for the whole screening period, and a potential compensatory drop in older women of 0.90 (95% CI: 0.88-0.96), yielding an overdiagnosis of 33%, which we consider the most reliable estimate. The drop in previously screened women was only present in one of the two screened regions and was small in absolute numbers. One in four breast cancers diagnosed in the screened age group in the Danish screening programme is overdiagnosed. Our estimate for Denmark is lower than that for comparable countries, likely because of lower uptake, lower recall rates and lower detection rates of carcinoma in situ.

/pdf/overdiagnosis-in-organised-mammography-screening-in-denmark-3zc7svg6co.pdf

Overdiagnosis in organised mammography screening in Denmark. A comparative study

Background
Unwanted hair growth is a therapeutic challenge and considerable resources are spent to achieve a hair-free appearance. Epilation with laser devices (alexandrite, diode, neodymium:YAG, and ruby lasers) and intense pulsed light are commonly used although the long-term effect is uncertain.

Objectives
To assess the effects of epilation with lasers and light sources.

Search methods
We searched the Cochrane Skin Group's Specialised Register in February 2004; MEDLINE (from 1966) and EMBASE (from 1980) in April 2005. We searched reference lists of collected trials and contacted trial authors.

Selection criteria
Randomised controlled trials of laser or photoepilation.

Data collection and analysis
Primary outcomes were objective reduction in hair counts, adverse effects and subjective reduction in hairiness. Secondary outcomes were participants´ satisfaction and personal observations such as softer, finer, or paler hairs. Two authors independently extracted data and assessed trial quality.

Main results
We included eleven randomised controlled trials involving 444 people, none of which were of high methodological quality. A large number of trials were excluded, mainly because of their non-randomised design. The randomisation procedures were either unclear or inadequate, using coin tossing, alternation, drawing lots or cards, or open tables of random numbers. The interventions and outcomes were too heterogeneous to be entered in a meta-analysis. Most trials examined a short-term effect up to six months after final treatment. There appeared to be a short-term effect of approximately 50% hair reduction with alexandrite and diode lasers up to six months after treatment, whereas little evidence was obtained for an effect of intense pulsed light, neodymium:YAG or ruby lasers. Long-term hair removal was not documented with any treatment. Pain, skin redness, swelling, burned hairs and pigmentary changes were infrequently reported adverse effects.

Authors' conclusions
Some treatments lead to temporary short-term hair removal. High quality research is needed on the effect of laser and photoepilation.

Laser and photoepilation for unwanted hair growth

Background
Alpha-1 antitrypsin deficiency is an inherited disorder that can cause chronic obstructive pulmonary disease (COPD). People who smoke are more seriously affected and have a greater risk of dying from the disease. Therefore, the primary treatment is to help people give up smoking. There are now also preparations available that contain alpha-1 antitrypsin, but it is uncertain what their clinical effect is.

Objectives
To review the benefits and harms of augmentation therapy with intravenous alpha-1 antitrypsin in patients with alpha-1 antitrypsin deficiency and lung disease.

Search methods
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed and ClinicalTrials.gov to 25 March 2016.

Selection criteria
We included randomised trials of augmentation therapy with alpha-1 antitrypsin compared with placebo or no treatment.

Data collection and analysis
The two review authors independently selected trials, extracted outcome data and assessed the risk of bias.

Main results
We included three trials (283 participants in the analyses) that ran for two to three years. All participants were ex- or never-smokers and had genetic variants that carried a high risk of developing COPD. Only one trial reported mortality data (one person of 93 died in the treatment group and three of 87 died in the placebo group). There was no information on harms in the oldest trial. Another trial reported serious adverse events in 10 participants in the treatment group and 18 participants in the placebo group. In the most recent trial, serious adverse events occurred in 28 participants in each group. None of the trials reported mean number of lung infections or hospital admissions. In the two trials that reported exacerbations, there were more exacerbations in the treatment group than in the placebo group, but the results of both trials included the possibility of no difference. Quality of life was similar in the two groups. Forced expiratory volume in one second (FEV1) deteriorated more in participants in the treatment group than in the placebo group but the confidence interval (CI) included no difference (standardised mean difference -0.19, 95% CI -0.42 to 0.05; P = 0.12). For carbon monoxide diffusion, the difference was -0.11 mmol/minute/kPa (95% CI -0.35 to 0.12; P = 0.34). Lung density measured by computer tomography (CT) scan deteriorated significantly less in the treatment group than in the placebo group (mean difference (MD) 0.86 g/L, 95% CI 0.31 to 1.42; P = 0.002). Several secondary outcomes were unreported in the largest and most recent trial whose authors had numerous financial conflicts of interest.

Authors' conclusions
This review update added one new study and 143 new participants, but the conclusions remain unchanged. Due to sparse data, we could not arrive at a conclusion about the impact of augmentation therapy on mortality, exacerbations, lung infections, hospital admission and quality of life, and there was uncertainty about possible harms. Therefore, it is our opinion that augmentation therapy with alpha-1 antitrypsin cannot be recommended.

/pdf/intravenous-alpha-1-antitrypsin-augmentation-therapy-for-4srdbo8wab.pdf

Intravenous alpha‐1 antitrypsin augmentation therapy for treating patients with alpha‐1 antitrypsin deficiency and lung disease

Aims To explore the rationale for claiming that benzodiazepines cause dependence while selective serotonin re-uptake inhibitors (SSRIs) do not.

Methods  We analysed the definitions of dependence and withdrawal reactions as they had appeared over time in the Diagnostic Statistical Manual of Mental Diseases (DSM) and the International Classification of Diseases (ICD). We also compared the discontinuation symptoms described for the two drug groups in a systematic review.

Results  The definition of substance dependence has changed over time in both the DSM and ICD. In the most recent classifications several criteria, including behavioural, physiological and cognitive manifestations, must be fulfilled. This change was published with the revision of the DSM-III revision in 1987 (DSM-IIIR), after the recognition of benzodiazepine dependence and just before the SSRIs were marketed in 1987–88. We found that discontinuation symptoms were described with similar terms for benzodiazepines and SSRIs and were very similar for 37 of 42 identified symptoms described as withdrawal reactions.

Conclusions  Withdrawal reactions to selective serotonin re-uptake inhibitors appear to be similar to those for benzodiazepines; referring to these reactions as part of a dependence syndrome in the case of benzodiazepines, but not selective serotonin re-uptake inhibitors, does not seem rational.

What is the difference between dependence and withdrawal reactions? A comparison of benzodiazepines and selective serotonin re-uptake inhibitors.

Surrogate outcome measures may speed up clinical research if they can be measured earlier in a study than the primary outcome of interest. We review the justification for their use and conclude that reliance on them may be harmful. Results obtained with surrogates should therefore be regarded as preliminary. Large, definitive trials with clinically relevant outcomes should always be performed before new interventions are accepted.

Peter C Gøtzsche

Papers

Overdiagnosis in organised mammography screening in Denmark. A comparative study

Laser and photoepilation for unwanted hair growth

Intravenous alpha‐1 antitrypsin augmentation therapy for treating patients with alpha‐1 antitrypsin deficiency and lung disease

What is the difference between dependence and withdrawal reactions? A comparison of benzodiazepines and selective serotonin re-uptake inhibitors.

Beware of Surrogate Outcome Measures