Incomplete Reporting of Recruitment Information
in Clinical Trials of Biologic Agents for the
Treatment of Rheumatoid Arthritis: A Review
ISMAIL SIMSEK
1
AND YUSUF YAZICI
2
Objective. It is important to evaluate how a randomized controlled trial (RCT) sample was assembled from the general
patient population in order to determine whether a patient differs from those who participated in the trial in a meaningful
way. The aim of this study is to assess the adequacy of reporting of the recruitment process of rheumatoid arthritis (RA)
patients participating in RCTs with biologic agents.
Methods. We searched PubMed for all reports of RCTs involving etanercept, infliximab, adalimumab, golimumab,
certolizumab, abatacept, tocilizumab, and rituximab in RA patients. Data recorded were eligibility fraction, enrollment
fraction, recruitment fraction, and number of patients needed to be screened (NNS) in order to randomize 1 participant.
Results. Of the 66 trials included in the analysis, 23 (35%) reported the number of individuals assessed by investigators
for eligibility, and 18 (27%) reported the number eligible for participation. Of the studies that reported quantitative
recruitment information, the median eligibility fraction was 80.6% (interquartile range [IQR] 71.8 –91.1%) and the median
enrollment fraction was 100% (IQR 88.4 –100%). The median NNS was found to be 1.28 (IQR 1.18 –1.43).
Conclusion. A substantial majority of RCTs conducted in RA patients with biologic agents did not provide sufficient
information about the patient recruitment process, which makes assessments of external validity difficult. The rate of
reporting of the recruitment process in this study was found to be lower as compared to similar studies conducted in
different specialties.
Introduction
Randomized controlled trials (RCTs) are regarded as the
gold standard for determining the effectiveness of medical
interventions (1). As also seen in RCTs done for other
diseases, RCTs conducted with biologic agents in rheuma-
toid arthritis (RA) patients generally describe outcomes
among participants with little consideration of whether
the seen effects can be generalized to larger patient popu-
lations who are frequently unlike those who participate in
RCTs (2).
Before applying the results of an RCT for treating an
individual patient, a clinician must determine whether his
or her patient differs from those who participated in the
trial in a meaningful way. Therefore, it is important to
evaluate how the RCT sample was assembled from the
general patient population.
The trial recruitment process can be described with
qualitative and quantitative data, of which both can con-
tribute important information about the generalizability.
In addition to being part of the good practice for the design
and conduct of trials, clear and sufficiently detailed report-
ing of participant flow is important in order to assess the
generalizability, relevance, and comparability of the trial
results.
The adequacy of reporting in RCTs has received in-
creased attention during the past 2 decades and culmi-
nated in the publication of a Consolidated Standards of
Reporting Trials (CONSORT) statement in 1996 (3). The
original CONSORT checklist focuses primarily on im-
proved reporting of information related to the internal
validity of an RCT. To enable better reporting of informa-
tion regarding external validity, the revised template for
the CONSORT flow diagram starts at the stage of asking
1
Ismail Simsek, MD: Gu ¨ lhane School of Medicine, An-
kara, Turkey;
2
Yusuf Yazici, MD: New York University
School of Medicine, New York University Hospital for Joint
Diseases, New York.
Dr. Simsek has received consultant fees, speaking fees,
and/or honoraria (less than $10,000 each) from Abbott and
Pfizer. Dr. Yazici has received consultant fees, speaking
fees, and/or honoraria (less than $10,000 each) from BMS,
Abbott, Genentech, Merck, and Pfizer.
Address correspondence to Ismail Simsek, MD, GATA Ro-
matoloji BD, 06018, Etlik, Ankara, Turkey. E-mail: drisimsek
@gmail.com.
Submitted for publication February 9, 2012; accepted in
revised form April 20, 2012.
Arthritis Care & Research
Vol. 64, No. 10, October 2012, pp 1611–1616
DOI 10.1002/acr.21721
© 2012, American College of Rheumatology
BRIEF REPORT
1611