Usefulness features
Figure 2 provides a bird’s eye view of binary usefulness features in
proportion to the total body of PTB trials (n=350) and according to
publication year and impact factor. In supplementary material (Table S4)
more details on the exact numbers and proportions are shown, split in
subgroups.
Problem base. The incidence of PTB <37weeks in
the control or placebo groups of the trials varied from 0-100% with a
median of 13.7% (IQR 7-30%) (Table S4 and Figure S2). This median is
comparable with the worldwide incidence of PTB of 11.1% (6), but the
range covers the full spectrum, including very low risk, high risk and
very high risk populations (i.e. triplet pregnancies).
Context placement. A total of 185/350 trials (53%, 95%CI
48-58%) justified the importance of their study in context of previous
systematic reviews (n=101/138 [73%] 95%CI 65-80% published ≧2010)
and 18/350 trials (5%, 95%CI 3-8%) performed a systematic review as
part of their study or included and updated meta-analyses.
Information gain. Information gain was deemed to be present in
192/350 trials (55%, 95%CI 50-60%). Absence of power calculations
decreased from 71/212 trials (34%) among those published before 2010 to
29 /138 trials (21%) among those published ≧2010 (RR 0.63, 95%CI
0.43-0.91) (Table 1). However, from the 250 trials reporting a power
calculation, calculations were incomplete and thus un-informative in 107
(43%, 95%CI 40-50%). Examples of non-informative power calculations:
‘we aimed for 80% power with an α of 0.05 and a β of 0.20’ ,
incoherent information ‘32 infants are necessary to reach a power
of 0.05% at the 80% confidence leve l’, or incomplete reporting on the
expected (absolute or relative) proportions of the primary outcome with
and without the intervention ‘we aimed for a 20% difference’ .
The aimed differences for prolongation of gestational age varied from 3
days till 14 days; and birthweight, from 80g till 1500g (Figure S2 and
Table S5). Use of composite or surrogate outcomes increased from 28/212
trials (13%) before 2010 to 34/138 trials (25%) ≧2010 (RR 1.87, 95%CI
1.19-2.93)(Table S4).
Pragmatism: A total of 17/350 trials (5%, 95%CI 3-8%)
employed a pragmatic design, with no difference over time in their
relative frequency.
Patient centeredness and value for money: No trials reported
involvement of mothers to reflect patients’ top priorities in research
questions or outcomes used. No value of information analysis was
reported in any final manuscript.
Feasibility: There were 113/350 trials (32%, 95%CI 28-37%)
that did not report their intended sample size, while 34/350 trials
(10%, 95%CI 7-13%) were unable to recruit their intended sample size
(not counting DSMB interference because of clear benefit or harm n=5).
Transparency: A total of 95/138 trials (69%, 95%CI 61-75%),
published ≧2010 were registered and a total of 38/138 (28%, 95%CI
21-36) were preregistered (registration before randomization of first
patient). Change over time using ≧ 2010 as a cut-off shows an increase
from 0.5% vs 28%, RR 58, 95% CI 8-420%. Protocols were available in
21/138 trials (15%, 95%CI 10-22%). Change over time shows an increase
from 0.5% to 15%, RR 32, 95% CI 4-237%. Data sharing statement was
reported in 11/138 (8%, 95%CI 5-14%) trials ≧2010 with an increase
from 2% to 8%, RR 3, 95% CI 1-10%.
A total of 255/350 trials (73%, 95%CI 68-77%) reported funding
sources and 151/350 (43%, 95%CI 38-48%) reported on conflicts of
interest.