Background
Methods
Meta-analysis selection and data collection process
Assessment of exposure and outcome
Results
Meta-analysis | Variables | |||
---|---|---|---|---|
First author | Year | Journal | Drug exposure | Outcome |
Weiss J [20] | 2017 | Ann Intern Med | Antihypertensive drugs | Harms outcomes: Cognitive impairment, quality of life, falls, fractures, syncope, functional status, hypotension, acute kidney injury, medication burden, withdrawal due to adverse events |
Bally M [21] | 2017 | BMJ | NSAIDs | Myocardial infarction |
Sordo L [22] | 2017 | BMJ | Opioid substitution treatment (methadone, buprenorphine) | All cause and overdose mortality |
Tariq R [23] | 2017 | JAMA Intern Med | Gastric acid suppressants | Recurrent Clostridium difficile infection |
Maruthur NM [24] | 2016 | Ann Intern Med | Diabetes monotherapy (thiazolidinediones, metformin, sulfonylureas, DPP-4 inhibitors, SGLT-2 inhibitors, GLP-1 receptor agonists) or metformin-based combinations | All-cause mortality, macrovascular and microvascular outcomes, intermediate outcomes (hemoglobin A1c, body weight, systolic blood pressure, heart rate), hypoglycemia, gastrointestinal side effects, genital mycotic infections, congestive heart failure |
Paul S [25] | 2016 | Ann Intern Med | Antiviral prophylaxis | Primary outcome: Hepatitis B Virus (HBV) reactivation Secondary outcomes: HBV-related hepatitis, interrupted chemotherapy, acute liver failure, mortality |
Li L [26] | 2016 | BMJ | Dipeptidyl peptidase-4 inhibitors | Heart failure |
Hospital admissions for heart failure | ||||
Molnar AO [27] | 2015 | BMJ | Generic immunosuppressive drugs | Patient survival, allograft survival, acute rejection, adverse events, bioequivalence |
Ziff OJ [28] | 2015 | BMJ | Digoxin | Primary outcome: All-cause mortality |
Secondary outcomes: Cardiovascular mortality; admission to hospital for any cause, cardiovascular causes and heart failure; incident stroke, incident myocardial infarction | ||||
CGESOC [29] | 2015 | Lancet | Hormone therapy (oestrogen, progestagen) | Ovarian cancer |
Bellemain- Appaix A [30] | 2014 | BMJ | Tienopyridines (clopidogrel) | Primary outcome: All-cause mortality, major bleeding Secondary outcomes: Major cardiovascular events and myocardial infarction, stroke, urgent revascularization, stent thrombosis |
Grigoriadis S [31] | 2014 | BMJ | Antidepressants (SSRIs) | Persistent pulmonary hypertension of the newborn |
Li L [32] | 2014 | BMJ | Incretin-based treatments | Pancreatitis |
Kalil AC [33] | 2014 | JAMA | Vancomycin MIC | All-cause mortality |
Stegeman BH [34] | 2013 | BMJ | Combined oral contraceptives | Venous thrombosis |
Maneiro JR [35] | 2013 | JAMA Intern Med | Biologic agents (abatacept, adalimumab, etanercept, golimumab, infliximab, rituximab) | Influence of AABs: on efficacy in immune-mediated inflammatory diseases (rheumatoid arthritis, juvenile idiopathic arthritis, inflammatory bowel disease, ankylosing spondylitis, psoriasis, psoriatic arthritis, or other spondyloarthropathies), in hypersensitivity reactions, and on the concentration of biological drugs; effect of concomitant treatment in development of AAB |
Hartling L [36] | 2012 | Ann Intern Med | Antipsychotics | Primary outcomes: Improved core symptoms of illness (positive and negative symptoms and general psychopathology), adverse events: diabetes mellitus, death, tardive dyskinesia, major metabolic syndrome |
Secondary outcomes: Functional outcomes, health care system use; response, remission and relapse rates; medication adherence, health-related quality of life, other patient-oriented outcomes (e.g. patient satisfaction), other adverse events: extrapyramidal symptoms, weight gain | ||||
Hsu J [37] | 2012 | Ann Intern Med | Antivirals (oseltamivir, zanamivir, amantadine, rimantadine) | Mortality, hospitalization, intensive care unit admission, mechanical ventilation and respiratory failure, duration of hospitalization, duration of signs and symptoms, time to return to normal activity, complications, critical adverse events: major psychotic disorders, encephalitis, stroke, seizure; important adverse events: pain in extremities, clonic twitching, body weakness, dermatologic changes (urticaria or rash); influenza viral shedding, emergence of antiviral resistance |
Caldeira D [38] | 2012 | BMJ | ACEIs and ARBs | Incidence of pneumonia |
Pneumonia related mortality | ||||
MacArthur GJ [39] | 2012 | BMJ | Opiate substitution, methadone detoxification | HIV infection among people who inject drugs |
Mantha S [40] | 2012 | BMJ | Progestin-only contaception | Venous thromboembolic events |
Silvain J [41] | 2012 | BMJ | Enoxaparin, unfractioned heparin | Primary outcome: Mortality, major bleeding Secondary outcomes: Composite ischaemic end point (death or myocardial infarction), complications of myocardial infarction, minor bleeding |
McKnight RF [42] | 2012 | Lancet | Lithium | Renal function, thyroid function, parathyroid function, hair disorders, skin disorders, bodyweight, teratogenicity |
Source of exposure and outcome data
Meta-analysis (MA) | Exposure assessment | Outcome assessment | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Data source presented in MA | Cohort studies (n) | Case-control studies (n) | Data source presented in MA | Cohort studies (n) | Case-control studies (n) | |||||||||
1ry | 2ry | NR | 1ry | 2ry | NR | 1ry | 2ry | NR | 1ry | 2ry | NR | |||
Weiss J [20] Harms outcomes | No | . | . | . | . | . | . | No | . | . | . | . | . | . |
Bally M [21] | Yes | 0 | 3b | 0 | 0 | 1 | 0 | Yes | 0 | 3b | 0 | 0 | 1 | 0 |
Sordo L [22] | Noa | . | . | . | . | . | . | Noa | . | . | . | . | . | . |
Tariq R [23] | Noac | . | . | . | . | . | . | Noa | . | . | . | . | . | . |
Maruthur NM [24] | Yesd | 0 | 3 | 0 | . | . | . | Yesd | 0 | 3 | 0 | . | . | . |
Paul S [25] | Noa | . | . | . | . | . | . | Noa | . | . | . | . | . | . |
Li L [26] Heart failure | Yes | 0 | 1 | 2 | 0 | 0 | 1 | Yes | 1 | 0 | 2 | 0 | 0 | 1 |
Li L [26] Hospital admissions for heart failure | Yes | 0 | 0 | 6 | 0 | 0 | 2 | Yes | 3 | 0 | 3 | 0 | 0 | 2 |
Molnar AO [27] | Noa | . | . | . | . | . | . | Noa | . | . | . | . | . | . |
Ziff OJ [28] | Noa | . | . | . | . | . | . | Noa | . | . | . | . | . | . |
CGESOC [29] | No | . | . | . | . | . | . | No | . | . | . | . | . | . |
Bellemain-Appaix A [30] | Noa | . | . | . | . | . | . | Noa | . | . | . | . | . | . |
Grigoriadis S [31] | Yes | 2 | 3 | 0 | 1 | 1 | 0 | Yes | 4 | 1 | 0 | 2 | 0 | 0 |
Li L [32] | Yes | 0 | 1 | 2 | 0 | 1 | 1 | Yes | 1 | 2 | 0 | 0 | 0 | 2 |
Kalil AC [33] | No | . | . | . | . | . | . | No | . | . | . | . | . | . |
Stegeman BH [34] | Yes | 0 | 9 | 0 | 8 | 8 | 1 | Yes | 4 | 5 | 0 | 5 | 12 | 0 |
Maneiro JR [35] | Noa | . | . | . | . | . | . | Noa | . | . | . | . | . | . |
Hartling L [36] | No | . | . | . | . | . | . | No | . | . | . | . | . | . |
Hsu J [37] | Noa | . | . | . | . | . | . | Noa | . | . | . | . | . | . |
Caldeira D [38] | Yes | 2 | 2 | 7 | 0 | 7 | 1 | Yes | 0 | 1 | 10 | 3 | 1 | 4 |
MacArthur GJ [39] | Noa | . | . | . | . | . | . | Noa | . | . | . | . | . | . |
Mantha S [40] | No | . | . | . | . | . | . | No | . | . | . | . | . | . |
Silvain J [41] | Yes | 0 | 7 | 0 | . | . | . | Yes | 0 | 7 | 0 | . | . | . |
McKnight RF [42] | No | . | . | . | . | . | . | No | . | . | . | . | . | . |
Source of data in the analysis of heterogeneity
Meta-analysis | Subgroup/ sensitivity analysis | Meta-regression analysis | ||||||
---|---|---|---|---|---|---|---|---|
Exposure-related variables | Outcome-related variables | Other variables | Type of data source included | Exposure-related variables | Outcome-related variables | Other variables | Type of data source included | |
Weiss J [20] Harms outcomes | . | . | . | No | . | . | . | No |
Bally M [21] | Timing of exposure to NSAIDs, dosage and duration of treatment, concomitant drug treatment | Comorbidities | Alternative statistical model, reason for exclusion | No | . | . | . | No |
Sordo L [22] | Time interval in and out of opioid substitution treatment | . | Alternative statistical model | No | Treatment provider, prevalence of opioid injection, average methadone dose | . | Mean age, percentage of men, location, percentage of inpatient induction, percentage loss to follow-up, midpoint follow-up period | No |
Tariq R [23] | Type of gastric acid suppressant (PPI and H2B reported together, PPI alone, or H2B alone) | Case definition (time interval of recurrence: within 60 days vs within 90 days), type of diagnostic assay used for Clostridium difficile infection | Study design, study setting (inpatients vs outpatients), data adjustment | No | . | . | . | No |
Maruthur NM [24] | Mode of therapy | . | . | No | . | . | . | No |
Paul S [25] Primary outcome | . | Chronic or resolved hepatitis B virus infection | Tumor and chemotherapy subtype, alternative statistical model, quality of design | No | . | . | . | No |
Paul S [25] Secondary outcomes | . | . | Alternative statistical model, quality of design | No | . | . | . | No |
Li L [26] | Type of control, mode of therapy, individual drugs | . | Length of follow up, type of design | No | . | . | . | No |
Molnar AO [27] | . | . | Type of design | No | . | . | . | No |
Ziff OJ [28] Primary outcome | . | . | Data adjustment, population type | No | Difference between digoxin and control arms at baseline: Diabetes, hypertension, diuretics, anti-arrhythmic drugs | . | Summary bias score, baseline study level variable: Year of publication, age, sex, previous myocardial infarction | No |
Ziff OJ [28] Secondary outcomes | . | . | . | No | . | . | . | No |
CGESOC [29] | Duration of use in current and past users of hormone therapy, types of hormone therapy | Tumour histology and malignant potential of the tumour | Study design, geographical region, age at first use of hormone therapy, age at menarche, parity, oral contraceptive use, height, bosy mass index, alcohol use, tobacco use, mother or sister with ovarian/breast cancer, histerectomy | No | . | . | . | No |
Bellemain-Appaix A [30] | Clopidogrel dose | Types of percutaneous coronary intervention | Type of design | No | . | . | . | No |
Grigoriadis S [31] | Timing of exposure to SSRIs | . | Study design, congenital malformations, control, meconium aspiration | No | . | . | . | No |
Li L [32] | Type of incretin agents, type of control, mode of therapy, individual incretin agents | . | Length of follow-up, alternative effect measure, alternative statistical model | No | . | . | . | No |
Kalil AC [33] | Different MIC cutoffs, assay type | Hospital or 30-d mortality | Publication year, quality of design | No | Vancomycin MIC cut-off, vancomycin exposure in the previous 6 months, vancomycin trough levels, proportion of patients who received vancomycin treatment | Control mortality, APACHE II score, Charlson score, duration of bacteremia, proportion of patients with endocarditis, proportion of patients located in the intensive care unit | Age | No |
Stegeman BH [34] | Generation of progestogen used in combined oral contraceptives, combined oral contraceptive pill | Method of diagnosis confirmation | Funding source, study design | Yes (outcome) | . | . | . | No |
Maneiro JR [35] | Type of biologic agent, concomitant treatment (monotherapy vs combined therapy), prior use of TNF inhibitors | Type of disease | Length of follow-up, data quality, study design, level of evidence of studies | No | Type of biologic agent, prior use of TNF inhibitors, method of measurement of antibodies, type of the anti-TNF monoclonal antibody | Type of disease, time of disease duration, time to assess response | Age and sex of patients, number of participants, length of follow-up, data quality, study design, level of evidence of studies | No |
Hartling L [36] Primary outcomes | Type of drug-comparison | Type of scale for the assessment of symptoms and quality of life | . | No | . | . | . | No |
Hartling L [36] Secondary outcomes | . | . | . | No | . | . | . | No |
Hsu J [37] | Individual drugs, dosage of antiviral, timing of treatment | . | Data adjustment, confirmed influenza, type of influenza A vs B, pandemic versus seasonal influenza, severity of influenza, age, pregnancy, baseline risk (e.g. immune-compromised), setting, funding conflict | No | . | . | . | No |
Caldeira D [38] Incidence of pneumonia | . | . | Study design, previous stroke, heart failure, chronic kidney disease, non-Asian patients | No | . | . | . | No |
Caldeira D [38] Pneumonia related mortality | . | . | Study design | No | . | . | . | No |
MacArthur GJ [39] | Duration of exposure to opiate substitution treatment | . | Data adjustment, geographical region, site of recruitment, monetary incentives, percentage of female participants, percentage of individuals from ethnic minorities | No | Exposure to methadone maintenance treatment at baseline only | . | Inclusion only of studies at lower risk of bias, inclusion only of studies that measured an incidence rate ratio, exclusion of studies that did not adjust for confounders | No |
Mantha S [40] | Route of administration | . | Data adjustment | No | . | . | . | No |
Silvain J [41] | Route of administration | . | Types of percutaneous coronary intervention, study publication, study size, quality of design | No | . | . | . | No |
McKnight RF [42] | . | . | . | No | . | . | . | No |