Background
Methods
Study sample
Search strategy | Hits | |
---|---|---|
#1 | sensitiva or diagnose or diagnosis or diagnostica in Clinical Trials | 70,052 |
#2 | randoma in Clinical Trials | 335,175 |
#3 | “study design” next “rct” in Clinical Trials | 150,275 |
#4 | (#2 OR #3) | 449,453 |
#5 | (#1 AND #4) | 50,419 |
#6 | (#5), from 2004 to 2007 | 12,892 |
Data extraction
1. Did methods of sequence generation adequately protect against selection bias?
Clear description of method for allocating participants to study groups. Quality judged as
Adequate
,
Inadequate
or
Unclear
using criteria recommended by the Cochrane Collaboration [31]. | |
2. Did methods of allocation concealment adequately protect against selection bias?
Clear description of method for preventing knowledge or prediction of group allocation amongst patients and care-providers. Quality judged as
Adequate, Inadequate
or
Unclear
using criteria recommended by the Cochrane Collaboration [31]. | |
3. Were participants, care-providers and outcome assessors blinded to test-treatment interventions?
Clear reports of whether participants, care-providers (those responsible for patient management) and outcome assessors were masked to the identity of tests used for decision-making, and a description of methods used to mask.
| |
4. Were primary outcomes comprehensively reported?
Reports considered
adequate
with clear definition of the primary outcome and description of method and timing of measurement. When the primary outcome was not clearly defined, the outcome used in the power calculation, or if not the outcome stated in the primary study objective was considered as primary. The primary outcome was as ‘not defined’ in the absence of this information [56]. Outcomes were classified as patient based or process.
Method of measurement considered
adequate
if a validated tool used, if non-validated but fully described tool used, or if rigorous criteria to assess outcome were provided (e.g. the operational definition of a target condition and test methods used to arrive at a diagnosis). Documentation considered
complete
when the time at which the primary assessment should be conducted was also made explicit.
| |
5. For each group, is it clear whether some participants did not receive the allocated intervention, were lost to follow-up, or were not analyzed?
Clear and complete accounting of participant flow as detailed in CONSORT [30], including use of a CONSORT diagram. Reporting considered
adequate
if all five elements (Eligibility, Allocation, Receiving intervention, Followed-up, Analyzed) were reported for all study groups, and if these numbers agreed (e.g. if the number analyzed tallied with the numbers randomized and lost to follow up).
Analysis according to allocated group
–considered
inadequate
if patients not analyzed according to allocated study group, regardless of test(s) actually received.
Use of intention-to-treat
(ITT)–clear statement that ITT principle was used. Considered
adequate
if all study patients were analyzed as randomized, and analyses were complete.
Exclusions and missing data
–Clear description of numbers and reasons for missing data due to: missing outcome responses, exclusion of participants, and loss to follow-up; Description of methods used to deal with missing data
Complete analysis
–Analyses considered
complete
when no data were missing due to exclusions, missing responses or loss to follow-up for the primary outcome measured at the primary time-point. Magnitude of attrition calculated per group for each trial by comparing numbers randomized to numbers analyzed. Differential attrition considered as ≥5% and ≥20% difference between arms, following the approach advocated by the Centre for Evidence Based Medicine when judging the quality of comparative evidence of effectiveness [57]. | |
6. Was the primary analyses conducted appropriately?
Whole group analysis
–Primary outcomes measured in subgroups of the randomized population were considered
Inadequate
due to risk of selection bias [58].
Inconsistency
–Use of different outcome assessment methods in each group considered
inadequate
unless the outcome was a measure of test performance (e.g. diagnostic yield or therapeutic yield).
| |
7. How did studies determine sample size?
Reporting of a power calculation and outcome variable on which it was based, extraction of target sample size and comparison to achieved sample size.
|
Results
Included trials
Outcomes
Outcome Type | Trials, n
| (%) |
aOutcome measurements, n
| (%) |
---|---|---|---|---|
Patient | ||||
Symptom score | 13 | (25) | 14 | (9) |
Adverse events | 8 | (15) | 15 | (10) |
Function | 8 | (15) | 11 | (7) |
Quality of life | 5 | (9) | 17 | (11) |
Mortality | 4 | (8) | 4 | (3) |
Health perception | 2 | (4) | 5 | (3) |
Psychological morbidity | 2 | (4) | 6 | (4) |
Absenteeism | 1 | (2) | 1 | (1) |
Clinical status | 9 | (17) | 9 | (6) |
Residual disease rate | 7 | (13) | 7 | (5) |
Recurrent disease rate | 6 | (11) | 7 | (5) |
Patient outcome total | 53 | (54) | 96 | (64) |
Process | ||||
Therapeutic yield | 17 | (45) | 20 | (13) |
Timing of care | 8 | (21) | 8 | (5) |
Cost | 7 | (18) | 7 | (5) |
Appropriateness of treatment decision | 5 | (13) | 6 | (4) |
Diagnostic yield | 4 | (11) | 5 | (3) |
Process outcome total | 38 | (39) | 46 | (31) |
Composite outcome | ||||
Adverse patient and process event rate | 7 | (7) | 7 | (5) |
Primary outcome not defined | 6 | (6) | 0 | (0) |
Total | 103 | (100) | 149 | (100) |
Risk of bias from randomization, blinding and loss to-follow-up
Trial Quality Item | Trials, n
| (%) |
---|---|---|
Randomized sequence allocation | ||
Adequate | 59 | (57) |
Inadequate | 2 | (2) |
Unclear | 42 | (41) |
Allocation concealment | ||
Adequate | 38 | (37) |
Inadequate | 3 | (3) |
Unclear | 62 | (60) |
Blinding | ||
Patients | 5 | (5) |
Care-providers | 4 | (4) |
Outcome assessors | 22 | (21) |
aSingle-blind | 20 | (19) |
bDouble-blind | 5 | (5) |
No blinding | 78 | (76) |
Reporting of primary outcome assessment | ||
Complete | 53 | (51) |
Partial | 33 | (32) |
Absent | 17 | (17) |
Reporting of participant flow | ||
Complete | 44 | (43) |
Partial | 58 | (56) |
Absent | 1 | (1) |
Missing data | ||
Complete | 41 | (40) |
Attrition ≤10% | 30 | (29) |
Attrition >10% | 25 | (24) |
Incomplete, cannot calculate | 4 | (4) |
Unclear if complete | 3 | (3) |
Differential attrition | ||
≥ 5% between arms | 16 | (16) |
≥ 20% between arms | 1 | (1) |
Intention-to-treat (ITT) | ||
Patients analyzed as randomized | 72 | (70) |
Complete or imputed data and analyzed as randomized | 30 | (29) |
Not conducted | 31 | (30) |
Inconsistent outcome assessment | 21 | (20) |
Inappropriate subgroup analysis | 9 | (9) |
Sample size | ||
Power calculation reported | 81 | (79) |
cMedian trial sample size [IQR] | 309 | [153–731] |
cMedian study arm sample size [IQR] | 166 | [72–297] |