Background
Methods
Searches
Study inclusion and exclusion criteria
Data extraction strategy
Domains (type of bias) | Review authors’ judgement | ||
---|---|---|---|
Low risk of bias | High risk of bias | Unclear risk of bias. | |
Random sequence generation (selection bias) | The investigators describe a random component in the sequence generation process such as drawing of lots | The investigators describe a nonrandom component in the sequence generation process. Usually, the description would involve some systematic, nonrandom approach | Insufficient information about the sequence generation process to permit judgement of “low risk” or “high risk” |
Allocation concealment (selection bias) | Participants and investigators enrolling participants could not foresee assignment because of the use of, for example, sequentially numbered, opaque, sealed envelopes to conceal allocation | Participants or investigators enrolling participants could possibly foresee assignments and thus introduce selection bias, such as allocation based on assignment envelopes used without appropriate safeguards (e.g., if envelopes were unsealed or nonopaque or not sequentially numbered) | Insufficient information to permit judgement of “low risk” or “high risk”. This is usually the case if the method of concealment is not described or not described in sufficient detail to allow a definite judgement – for example, if the use of assignment envelopes is described, but it remains unclear whether envelopes were sequentially numbered, opaque and sealed |
Blinding of participants and personnel (performance bias) | Any one of the following: • No blinding or incomplete blinding, but the review authors judge that the outcome is not likely to be influenced by lack of blinding • Blinding of participants and key study personnel ensured, and unlikely that the blinding could have been broken | Any one of the following: • No blinding or incomplete blinding, and the outcome is likely to be influenced by lack of blinding • Blinding of key study participants and personnel attempted but likely that the blinding could have been broken, and the outcome is likely to be influenced by lack of blinding | Any one of the following: • Insufficient information to permit judgement of “low risk” or “high risk” • The study did not address this outcome |
Blinding of outcome assessment (detection bias) | Any one of the following: • No blinding of outcome assessment, but the review authors judge that the outcome measurement is not likely to be influenced by lack of blinding • Blinding of outcome assessment ensured, and unlikely that the blinding could have been broken | Any one of the following: • No blinding of outcome assessment, and the outcome measurement is likely to be influenced by lack of blinding • Blinding of outcome assessment, but likely that the blinding could have been broken, and the outcome measurement is likely to be influenced by lack of blinding | Any one of the following: • Insufficient information to permit judgement of “low risk” or “high risk” • The study did not address this outcome |
Incomplete outcome data (attrition bias) | Any one of the following: • No missing outcome data • Reasons for missing outcome data unlikely to be related to true outcome (for survival data, censoring unlikely to be introducing bias) • Missing outcome data balanced in numbers across intervention groups, with similar reasons for missing data across groups • For dichotomous outcome data, the proportion of missing outcomes compared with observed event risk not enough to have a clinically relevant impact on the intervention effect estimate • For continuous outcome data, plausible effect size (difference in means or standardized difference in means) among missing outcomes not enough to have a clinically relevant impact on observed effect size • Missing data have been imputed using appropriate methods. | Any one of the following: • Reason for missing outcome data likely to be related to true outcome, with either imbalance in numbers or reasons for missing data across intervention groups • For dichotomous outcome data, the proportion of missing outcomes compared with observed event risk enough to induce clinically relevant bias in intervention effect estimate • For continuous outcome data, plausible effect size (difference in means or standardized difference in means) among missing outcomes enough to induce clinically relevant bias in observed effect size • “As-treated” analysis done with substantial departure of the intervention received from that assigned at randomization • Potentially inappropriate application of simple imputation. | Any one of the following: • Insufficient reporting of attrition/exclusions to permit judgement of “low risk” or “high risk” (e.g., number randomized not stated, no reasons for missing data provided) • The study did not address this outcome. |
Extraction fields | Type of interventions | |||
---|---|---|---|---|
Pharmacological (drugs and nutritional supplements) | Nonpharmacological (rehabilitation, behavioral treatment, education, psychotherapy) | Surgical procedures and medical devices (disposal or implementable) | Other (e.g., therapeutic strategies) | |
Setting (location and type of infrastructure delivering the intervention) | x | x | x | x |
Dose | x | |||
Mode of administration (e.g., oral versus intravenous) | x | |||
Timing | x | |||
Duration of treatment | x | |||
Treatment adherence | x | x | ||
Intervention development process | x | |||
Intervention content (components) | x | |||
Equipment or materials used or provided (physical or informational) | x | x | ||
Mode of implementation (e.g., individually versus in groups) | x | |||
Schedule (frequency or intensity, timing and duration) | x | |||
Care provider background | x | x | x | |
Pre-(operative) care | x | x | ||
Anesthesia | x | |||
Procedure (sequencing of the technique) | x | x | ||
Post-(operative) care | x | x |
Data analysis
Results
Reports identification
Study characteristics
Characteristics |
N = 121 |
---|---|
Trial location | |
Sub-Saharan countries only | 104 (85.9) |
• South Africa | 20 (19.2) |
• Nigeria | 12 (11.5) |
• Tanzania | 10 (9.6) |
• Kenya | 8 (7.6) |
• Uganda | 8 (7.6) |
• Malawi | 6 (5.7) |
• Rwanda | 4 (3.8) |
• Ethiopia | 3 (2.8) |
Several Sub-Saharan countries | 5 (4.1) |
Sub-Saharan African countries and high-income countries (HICs) or other countries (not HICs) | 12 (8.9) |
Medical area | |
Malaria | 25 (20.6) |
HIV/AIDS | 24 (19.9) |
Tuberculosis | 4 (3.3) |
Diarrheal diseases | 3 (2.4) |
Preterm birth complications | 2 (1.6) |
Other diseases | 63 (52.2) |
Study design | |
Parallel groups | 97 (80.1) |
Clusters | 19 (15.8) |
Factorial design | 3 (2.4) |
Cross-over | 2 (1.7) |
Experimental intervention | |
Pharmacological (drugs and nutritional supplements) | 74 (61.1) |
Nonpharmacological | 47 (38.9) |
• Participative interventions | 40 (85.1) |
• Devices | 3 (6.3) |
• Surgical procedures | 1 (2.3) |
• Therapeutic strategies | 3 (6.3) |
Comparator | |
Active treatment | 43 (35.5) |
Usual care | 32 (26.4) |
Placebo | 24 (19.9) |
Other | 22 (18.2) |
Sample size (median [IQR]) | 346 [160–932] |
Inadequate methods and risk of bias in RCTs
Domains | Type of problem in original trial report |
N = 121 No. (%) | Methodological adjustment | Cost |
---|---|---|---|---|
Generation of randomization sequence | Inappropriate randomization methods including sequence generated by some rule based on date/day of admission or on hospital or clinic record number | 5 (4) | Referring to a random number table; Using a computer random-number generator Coin tossing Shuffling cards or envelopes Throwing dice Drawing of lots | No cost |
Allocation concealment | No explicitly unconcealed procedure or unsealed or nonopaque or not sequentially numbered envelopes | 10 (8) | Central allocation (including telephone, web-based and pharmacy-controlled randomization) or sequentially numbered, opaque, sealed envelopes | Minor |
Incomplete outcome data | Exclusion of patients from the analysis | 14 (11) | Intention-to-treat analysis | No cost |
Intention-to-treat analysis but inadequate missing data imputation | 2 (1) | Intention-to-treat analysis with a multiple imputation method | Minor |