Transcript - LSTM Online Archive

Methodological quality of malaria RCTs conducted in Africa
Vittoria Lutje*^, Annette Gerritsen**, Nandi Siegfried***.
*Cochrane Infectious Diseases Group (CIDG), Liverpool, UK; **Department of Public Health, University of Venda, Thohoyandou, South Africa
*** South African Cochrane Centre, Medical Research Council, CapeTown, South Africa. ^ Corresponding author, email: [email protected]
Background
Methods
Good methodological quality is necessary to reduce risk of bias (RoB) in
randomized controlled trials (RCTs) and in meta-analysis. As part of a
review of clinical and methodological characteristics of malaria RCTs
conducted in Africa, we assessed RoB of trials conducted after the
publication of the original CONSORT statement in 1996 (1). This was a
novel analysis that can highlight training needs for clinicians conducting
trials in potentially resource-limited settings.
Malaria RCTs conducted in African countries were identified through
systematic searches of electronic databases (Medline, Embase,
CENTRAL, LILACS) run in August 2007. From the total abstract
dataset we extracted key characteristics on each trial and then
drew a random sample of these. Reports of RCTs in the random
sample were analysed using a standardized data extraction form.
We evaluated trial reports published between 1997 and 2007 for risk
of bias according to 4 domains (randomized sequence generation,
allocation concealment, blinding, and loss to follow-up).
Objectives
To analyse the RoB of malaria RCTs conducted in Africa between 1997
and 2007, according to 4 characteristics (sequence generation,
allocation concealment, blinding, and loss to follow-up).
Country distribution of malaria RCTs
Results
We identified 943 reports of malaria trials run in Africa from 1948 to
2007, and we drew a random sample of 176 records. Trial key
characteristics in the sample were representative of the overall
dataset. The geographical distribution of the trials is shown in Fig 1;
main clinical characteristics of the trials are reported elsewhere
(2). There were 60 RCTs published between 1997 and 2007 and
included in the Risk of bias analysis (Table 1). Sequence generation
was considered adequate (done by using a random numbers table or
electronically generated) in 35 reports. It was not clearly reported
in 21 trials. Many RCTs reports did not mention methods of
allocation concealment or whether participants or intervention
providers were blinded. In contrast, loss to follow-up was
accounted for in most trial reports (49 out of 60).
Risk of bias of malaria RCTs run in Africa between 1997 and 2007
Sequence
generation
Allocation
concealment
Blinding
Loss to follow
up
Adequate Not
Unclear
adequate
35
3
21
Not done
0
Not
possible
0
14
0
36
10
0
23
0
27
8
2
49
0
11
0
0
Conclusions
The quality of African malaria trials reports was not consistent among the 4 domains analysed: a large proportion of RCTs had a high risk of bias
for blinding and allocation concealment, but loss to follow-up was mostly adequately reported. Methods of randomization were adequate in most
reports. Suboptimal reporting of methodological characteristics has been widely reported for trials in different healthcare areas, potentially
affecting the validity of the results and the estimate of treatment effects. A high RoB is not only associated with trials conducted in resourcepoor settings or with older trials: recent RCTs have often been found to be also poorly reported. There is still a need for education about the
CONSORT statement. Prospective registration of trials and detailed instructions to trialists may help.
References
1. Begg C, Cho M, Eastwood S, Horton R, Moher D, Olkin I, et al (1996). Improving the quality of reporting of randomized controlled trials: the CONSORT statement. JAMA 276: 637-9.
2. Lutje V, Gerritsen A, Siegfried N (2011). Randomized controlled trials of malaria intervention trials in Africa, 1948 to 2007: a descriptive analysis. Malaria Journal 10:61
Acknowledgements: This work was supported by the Cochrane Infectious Diseases Group and Effective Health Care Research Programme Consortium (at LSTM) funded by the Department for
International Development UK (DFID); and the PACTR grant funded by the European and Developing Countries Clinical Trials Partnership (EDCTP).