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Special Collection

Network meta-analysis

Special Collection

With the increasing number of competing interventions available for a given health condition, Cochrane Review authors are pushed towards focusing on multiple pairwise comparisons. However, standard pairwise meta-analysis may not answer the questions of interest to patients and clinicians, because standard meta-analysis can compare only two treatments and only if they have been compared directly in clinical trials. Network meta-analysis allows indirect inference for comparisons that have never been made in individual studies. It also allows ranking of the competing interventions according to their effectiveness or safety.[1]

A key assumption underlying indirect comparisons and network meta-analyses is that the anchor interventions are similar enough to be considered equivalent across trials that compare different sets of interventions. In other words, all included interventions should be jointly randomisable, such that a participant in any trial that meets all inclusion criteria could have, in principle, been randomised to any of the interventions being compared.[2]

The Cochrane Database of Systematic Reviews is a major source of meta-analyses involving indirect comparisons or network meta-analysis.[3] To encourage the proper application of network meta-analysis in Cochrane Reviews, the Cochrane Comparing Multiple Interventions Methods Group ( was formed to provide guidance for Cochrane Review authors. This Special Collection highlights some Cochrane Reviews in which network meta-analysis was used. The aim is to provide a quick overview of the types of research questions that can be addressed by network meta-analysis, how the networks are formed, and how the methods and results are presented. Interested authors should involve a statistician in applying network meta-analysis method in their review.

Cochrane Reviews using network meta-analysis

Free Access
Oral antiviral therapy for prevention of genital herpes outbreaks in immunocompetent and nonpregnant patients
Genital herpes is caused by herpes simplex virus 1 (HSV-1) or 2 (HSV-2). Some infected people experience outbreaks of genital herpes, typically characterised by vesicular and erosive localised painful genital lesions. This review compares the effectiveness and safety of three oral antiviral drugs (aciclovir, famciclovir, and valaciclovir) prescribed to suppress genital herpes outbreaks in non-pregnant patients.
Free Access
Immunomodulators and immunosuppressants for multiple sclerosis: a network meta‐analysis

There are several therapeutic strategies for the treatment of multiple sclerosis, including immunosuppressants, immunomodulators, and monoclonal antibodies. Their relative effectiveness in the prevention of relapse or disability progression is unclear due to the limited number of direct comparison trials. A summary of the results, including both direct and indirect comparisons of treatment effects, may help to clarify the above uncertainty. This review estimates the relative efficacy and acceptability of interferon ß-1b, interferon ß-1a, glatiramer acetate, natalizumab, mitoxantrone, methotrexate, cyclophosphamide, azathioprine, intravenous immunoglobulins, and long-term corticosteroids versus placebo or another active agent in participants with multiple sclerosis. It ranks the treatments according to their effectiveness and risk-benefit balance.

Methods to decrease blood loss during liver resection: a network meta‐analysis
Liver resection is a major surgery with significant mortality and morbidity. Various methods have been attempted to decrease blood loss and morbidity during elective liver resection. These methods include different methods of vascular occlusion, parenchymal transection, and management of the cut surface of the liver. A surgeon typically uses only one of the methods from each of these three categories, but the optimal treatment strategy for liver resection is unknown. This review compares the benefits and harms of different treatment strategies to decrease blood loss during elective liver resection.
Free Access
Combined oral contraceptives: the risk of myocardial infarction and ischemic stroke
Combined oral contraceptives (COCs) have been associated with an increased risk of arterial thrombosis, i.e. myocardial infarction or ischemic stroke. However, as these diseases are rare in young women and as many types of combined oral contraception exist, the magnitude of the risk and the effect of different hormonal contents of COC preparations remain unclear. This review aims to estimate the risk of myocardial infarction or ischemic stroke in users compared with non-users of different types, doses and generations of combined oral contraception.
Free Access
Long‐acting inhaled therapy (beta‐agonists, anticholinergics and steroids) for COPD: a network meta‐analysis
Pharmacological therapy for chronic obstructive pulmonary disease (COPD) is aimed at relieving symptoms, improving quality of life, and preventing or treating exacerbations. Treatment tends to begin with one inhaler, and additional therapies are introduced as necessary. For persistent or worsening symptoms, long-acting inhaled therapies taken once or twice daily are preferred over short-acting inhalers. Several Cochrane Reviews have looked at the risks and benefits of specific long-acting inhaled therapies compared with placebo or other treatments. However, for patients and clinicians, it is important to understand the merits of these treatments relative to each other, and whether a particular class of inhaled therapies is more beneficial than the others. This review assesses the efficacy of treatment options for patients whose chronic obstructive pulmonary disease cannot be controlled by short-acting therapies alone. The review does not look at combination therapies usually considered later in the course of the disease. This network meta-analysis addresses the following issues: (1) How does long-term efficacy compare between different pharmacological treatments for COPD? (2) Are there limitations in the current evidence base that may compromise the conclusions drawn by this network meta-analysis? If so, what are the implications for future research?
Free Access
Immunomodulators and immunosuppressants for relapsing‐remitting multiple sclerosis: a network meta‐analysis
Different therapeutic strategies are available for the treatment of people with relapsing-remitting multiple sclerosis (RRMS), including immunomodulators, immunosuppressants and biologics. Although there is consensus that these therapies reduce the frequency of relapses, their relative benefit in delaying new relapses or disability worsening remains unclear due to the limited number of direct comparison trials.  This review aims to compare the benefit and acceptability of interferon beta-1b, interferon beta-1a, glatiramer acetate, natalizumab, mitoxantrone, fingolimod, teriflunomide, dimethyl fumarate, alemtuzumab, pegylated interferon beta-1a, daclizumab, laquinimod, azathioprine and immunoglobulins for the treatment of people with RRMS and to provide a ranking of these treatments according to their benefit and acceptability.
Free Access
Combined oral contraceptives: venous thrombosis
The use of combined oral contraceptives has been associated with venous thrombosis (i.e. deep venous thrombosis and pulmonary embolism). This risk has been evaluated for many estrogen doses and progestogen types contained in combined oral contraceptives, but there is no comprehensive comparison involving commonly used combined oral contraceptives. This review provides a comprehensive overview of the risk of venous thrombosis in women using different combined oral contraceptives.
Fluoride toothpastes of different concentrations for preventing dental caries in children and adolescents
Caries (dental decay) is a disease of the hard tissues of the teeth caused by an imbalance, over time, in the interactions between cariogenic bacteria in dental plaque and fermentable carbohydrates (mainly sugars). The use of fluoride toothpaste is the primary intervention for the prevention of caries. The aim of this review is to determine the relative effectiveness of fluoride toothpastes of different concentrations in preventing dental caries in children and adolescents, and to examine the potentially modifying effects of baseline caries level and supervised toothbrushing.
Bisphosphonates in multiple myeloma: an updated network meta‐analysis
Bisphosphonates are specific inhibitors of osteoclastic activity and are used in the treatment of patients with multiple myeloma. While bisphosphonates are effective in reducing vertebral fractures and pain, their role in improving overall survival remains unclear. This review assesses the evidence related to benefits and harms associated with use of various types of bisphosphonates (aminobisphosphonates versus non-aminobisphosphonates) in the management of people with multiple myeloma. The primary objective was to determine whether adding bisphosphonates to standard therapy in multiple myeloma improves overall survival and progression-free survival, and decreases skeletal-related morbidity. The secondary objectives were to determine the effects of bisphosphonates on pain, quality of life, incidence of hypercalcaemia, incidence of bisphosphonate-related gastrointestinal toxicities, osteonecrosis of jaw, and hypocalcaemia.
Free Access
Erythropoiesis‐stimulating agents for anaemia in adults with chronic kidney disease: a network meta‐analysis
Several erythropoiesis-stimulating agents (ESAs) are available for treating anaemia in people with chronic kidney disease. Their relative efficacy (preventing blood transfusions and reducing fatigue and breathlessness) and safety (mortality and cardiovascular events) are unclear due to the limited power of head-to-head studies. This review compares the efficacy and safety of ESAs (epoetin alfa, epoetin beta, darbepoetin alfa, or methoxy polyethylene glycol-epoetin beta, and biosimilar ESAs, against each other, placebo, or no treatment) to treat anaemia in adults with chronic kidney disease.