A cohort examination to establish reporting of the remit and function of Trial Steering Committees in randomised controlled trials
Conroy et al. Trials
A cohort examination to establish reporting of the remit and function of Trial Steering Committees in randomised controlled trials
Elizabeth J. Conroy 0 1
Barbara Arch 0
Nicola L. Harman 0 1
J. Athene Lane 2
Steff C. Lewis 5
John Norrie 5
Matthew R. Sydes 3 4
Carrol Gamble 0 1
0 Clinical Trials Research Centre, University of Liverpool , Liverpool , UK
1 MRC North West Hub for Trials Methodology Research, Department of Biostatistics, University of Liverpool , Block F Waterhouse Building, 1-5 Brownlow Street, Liverpool L69 3GL , UK
2 Bristol Randomised Trials Collaboration, University of Bristol , Bristol , UK
3 London MRC Hub for Trials Methodology Research , London , UK
4 MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, UCL , London , UK
5 Centre for Population Health Sciences, Edinburgh University , Edinburgh , UK
Background: The DAMOCLES project established a widely used Data Monitoring Committee (DMC) Charter for randomised controlled trials (RCTs). Typically, within the UK, the DMC is advisory and recommends to another executive body; the Trial Steering Committee (TSC). Despite the executive role of the TSC, the CONSORT Statement does not explicitly require reporting of TSC activity, although is included as an example of good reporting. A lack of guidance on TSC reporting can impact transparency of trial oversight, ultimately leading to a misunderstanding regarding role and, subsequently, further variation in practice. This review aimed to establish reporting practice of TSC involvement in RCTs, and thus make recommendations for reporting. Methods: A cohort examination identifying reporting practice was undertaken. The cohort comprised RCTs published in three leading medical journals (the British Medical Journal, The Lancet and the New England Journal of Medicine) within 6 months in 2012 and the full NIHR HTA Monograph series. Details of TSC constitution and impact were extracted from main publications and published supplements. Results: Of 415 publications, 264 were eligible. These were typical in terms of trial design. Variations in reporting between journals and monographs was notable. TSC presence was identified in approximately half of trials (n = 144), of which 109 worked alongside a DMC. No publications justified not convening a TSC. When reported, the role of the committee and examples of impact in design, conduct and analysis were summarised. Conclusions: We present the first review of reporting TSC activity in the published academic literature. An absence of reporting standards with regards to TSC constitution, activity and impact on trial conduct was identified which can influence transparency of reporting trial oversight. Consistent reporting is vital for the benefits and impact of the TSC role to be understood to support adoption of this oversight structure and reduce global variations in practice.
Trials; Oversight committee; Trial Steering Committee; Executive Committee; Clinical Trial; Data Monitoring Committee; Randomised controlled trial
The DAMOCLES project [
] established a Data Monitoring
Committee Charter [
] which has been widely used for
randomised controlled trials since 2005. As established
within DAMOCLES, the Data Monitoring Committee
(DMC) is typically advisory and makes recommendations
to another executive body; considered the Trial Steering
Committee (TSC). Currently however, no evidence-based
Charter exists for TSCs to establish their role and
functionality in RCTs.
The MRC Guidelines for Good Clinical Practice
(1998) defined a three-committee oversight structure:
the day-to-day Trial Management Group, the DMC
and the executive TSC [
]. This document provided
guidance and a suggested terms of reference for TSCs
which has been widely adopted within the UK [
However, a need for redevelopment and expansion of
these guidelines has been identified [
]. This may
have led to these guidelines recently being withdrawn,
and subsequently revised, with limited changes mainly
concerning responsibilities to funder. The need for
the development of expanded universal guidelines
Both DAMOCLES [
] and the Consolidated Standards
of Reporting Trials (CONSORT) Statement [
evidence-based minimum set of recommendations for
reporting randomised trials, recommend that trial
reports should include information about interim
analyses and the data monitoring process. The purpose of
CONSORT is to facilitate the complete and transparent
reporting of trials and, as such, has been widely adopted
by journals to aid critical appraisal and interpretation.
However, there is an absence of content focussing on
the clinical trial oversight structure and responsibilities
for decision-making. While reporting of DMC activity is
included within CONSORT as part of reporting interim
analyses, and DAMOCLES suggests reporting DMC
membership, the reporting of TSC activities is not
The objective of this cohort examination was to
establish current practice of reporting of TSC involvement in
RCTs, to recommend reporting standards for TSC
activity and to identify impact on trial conduct.
EJC searched publications within a 6-month period (1
July 2012 to 31 December 2012) from four sources.
Three top general medical journals (the British Medical
Journal (BMJ), The Lancet (Lancet) and the New England
Journal of Medicine (NEJM)) and within the full UK
National Institute for Health Research Health Technology
Assessment (NIHR HTA) Monograph series. Journals
were selected that are known for endorsing high standards
of reporting when publishing RCTs. The NIHR HTA
Monograph series (HTA), a peer-reviewed, open-access
journal that publishes full details of a single study funded
by the NIHR HTA funding stream. NIHR HTA is a major
UK funding body which supports policy-makers such as
the National Institute for Health and Care Excellence, the
National Screening Committee and the Department of
]. The full NIHR HTA Monograph series
was searched as opposed to those published within
the set timeframe because this series has a suggested
word count of 50,000 and so enables more details of
the work to be included when compared to a typical
peer-reviewed journal and so were considered more
likely to provide a comprehensive description of TSC remit
and function. Therefore, when summarising examples of
reporting, results from journals and monographs are
Published RCTs were identified by searching of titles,
abstracts and keywords of primary research papers
published within the timeframe using the search term
random*. When eligibility was unclear a second reviewer
(CG) was consulted.
We included all RCTs publishing main trial results.
Articles presenting results of: secondary analyses;
preliminary analyses; and additional reports of published
RCTs; for example, results of long-term follow-up,
Data extraction and analysis
A Data Extraction Form was designed and piloted by
EJC and CG. Data was extracted from all published
materials (main trial report and supplementary material
when applicable). EJC extracted data on trial design, trial
stopping and oversight committee reporting (see Table 1)
and entered into an MS Access database. BA
independently extracted data from a random 10%, stratified by
TSC reporting and source.
Quantitative items were analysed using descriptive
statistics. Standard statistical software was used throughout
(Statistical Analysis Software (SAS 9.1.3; SAS Institute Inc.,
Cary, NC, USA)). Text extracts from articles were examined
using NVivo qualitative data analysis software (QSR
International Pty Ltd. Version 10, 2012). EJC and CG identified
themes within text items which were used to contextualise
and illuminate quantitative results. Extracts are denoted by
(…) and (words) denoted the addition of words or replaced
words to aid understanding. Each paper was mapped to a
unique project identification number; details of this mapping
are given in Additional file 1: Table S1. Due to differences in
focus of paper between journal manuscripts and the
monograph series, results are presented split by source and, where
applicable, split into sections appropriate for the content.
5.3. If applicable, has the absence of committees been justified? If yes,
DMC Data Management Committee, HTA Health Technology Assessment
Monograph series, TSC Trial Steering Committee
Eligible cohort and demographics
Journals were searched in May 2013. The search
returned 415 hits, of which 264 (63.6%) were eligible
(127 HTA; 16 BMJ; 66 Lancet; 55 NEJM). Figure 1
provides further details. Trial funders were geographically
distributed with the majority being of UK (n = 161,
61.0%) or USA (n = 50, 18.9%) origin. Typically trials
were parallel (n = 233, 88.3%), two-armed, (n = 185,
70.1%) with a pharmaceutical intervention (n = 132,
50.0%) and blinded (n = 162, 61.4%). Patients were
individually randomised (n = 237, 90.5%) within the
secondary and/or tertiary setting (n = 128, 48.5%). Other design
features and characteristics, overall and split by source,
are summarised in Table 2.
Variations in published material
Due to variations in publishing requirements, differences
were anticipated between monographs and journals.
However, there were clear differences between sources,
Key journals were restricted by word count though
supplements were often published. While all three journals
encouraged protocol and supplementary appendices, this
appeared to be endorsed by the NEJM only. Further
details are provided in Table 3.
Trial oversight committees
Table 4 describes level of TSC and DMC reporting split
by publication source.
Publications reporting neither a TSC nor DMC (71/264,
26.9%) varied by source from 7% (NEJM, 4/55) to 63%
(BMJ, 10/16). Only NEJM and HTA publications justified
no DMC. NEJM publications justifying no DMC (n = 2)
gave reason in the published protocol as a supplement
stating that the DMC was not applicable (NEJM16) and:
‘A data monitoring committee for efficacy is not
required for this study. Data safety monitoring will be
conducted on an ongoing basis as detailed in the
Safety Review Plan’. (NEJM44)
HTA publications justifying not having a DMC (n =
3) gave reasons: the trial examined routine therapies
(HTA67); no interim analyses were planned (HTA83)
and the trial did not involve a medicinal product
Of the 120 trials not explicitly reporting use of a TSC,
none justified its absence.
Aside from trials with cellular or gene therapy
interventions of which there were few, TSCs were
consistently reported regardless of intervention type, from 48%
of psychological or behavioural intervention trials (14/
29) to 79% physical intervention trials (11/14). DMCs
were reported less frequently, from 23% in resources
and infrastructure trials (5/22) to 73% in pharmaceutical
intervention trials (97/132) or medical device trials (19/
26). Trials with neither committee most commonly
involved a complimentary intervention (3/6, 50%) or
psychological and behavioural (13/29, 45%). Further details
are provided in Tables 5 and 6.
Trial steering committees
Trial Steering Committee was the most common TSC
name (61/144, 42%). Other variants were Steering
Committee (42/144, 29%); Steering Group (14/144, 10%)
and Executive Committee (10/144, 7%). Table 7 shows
Four fifths indicated the number of committee members,
varying from half (BMJ, 3/6) to 85% (HTA, 71/84). The
number of members ranged from 2 to 52 with a median
of 7. Details are provided in Table 8.
One hundred and ten publications listed members
of which 84 specified a Chair. Other roles or fields of
expertise were detailed in almost half of trials with a
TSC (66/144). Common representation were clinical
(n = 46), statistical (n = 29) and patient and/or public
(PPI) (n = 39).
Reporting was unclear with regards to membership
Journal manuscripts One publication specified that the
funder (NIHR) appointed the TSC, stating that members
were ‘researchers independent of the study funders,
although several have served on their advisory or funding
One publication indicated voting members when
listing members (Lancet25).
Ten NEJM publications gave details of TSC
membership beyond listing members and affiliations. Half of
these described sponsor representation, with one
specifying this representation as none voting (NEJM20).
All 32 (9 Lancet, 23 NEJM) supplements reporting
TSCs listed members and/or affiliations.
Thirteen NEJM protocols discussed committee
membership. Protocol reporting consisted listing
members by role and/or field of expertise (n = 10) or
by name (n = 6), of which three reported both.
Monographs Forty-six gave details of TSC membership
beyond listing members and affiliations.
Independence was discussed in 32 publications (32/
46, 69.6%), of which 30 specified an independent Chair.
Two reported funder input in selecting the Chair.
Members represented the following fields: clinical
(n = 12), PPI (n = 6), statistical (n = 3) and health
BMJ British Medical Journal, HTA Health Technology Assessment Monograph series, NEJM New England Journal of Medicine
aAdvertisements in newsletters (n = 1); Child and Adolescent Mental Health Services (n = 1); Community mental health teams (n = 1); Community nurse services
(n = 1); Community nursing services and community leg ulcers clinics (n = 1); Community old age psychiatry services (n = 1); Community sources (n = 1);
Department of Veterans Affairs (n = 3); National population registrar (n = 1); Community paediatricians (n = 1); Registrar (n = 3); Schools (n = 1); Secondary schools
(n = 1); University podiatry schools and podiatry clinics (n = 1); Vaccination centres in schools (n = 1); Villages (n = 1); Not specified (n = 8)
bOther setting: Veterans Affairs Medical Centre (n = 1); From other trials (n = 1)
cNot clear: Adult mental health setting (n = 1); Antenatal clinic (n = 1); Centres (n = 29); Child and Adolescent Mental Health Services (n = 1); Child Development
Centre (n = 1); Clinic site (n = 1); Clinical centres (n = 1); Clinical sites (n = 1), Clinics (n = 2); Countries (n = 2); European medical centres (n = 1); Institutes (n = 1);
Institutions (n = 1); Sites (n = 13); Not described (n = 7)
dTotal arms equal to: six (n = 2); eight (n = 1); nine (n = 1); twelve (n = 1)
eDefined by UK Clinical Research Collaboration Health Research Classification System
fCategories not mutually exclusive
gBoth: Composite (n = 3) (Disease improvement calculated from CHAQ, physician’ global assessment of disease activity, parents’ global assessment of overall
wellbeing, number of joints with limited range of movement (ROM), number of active joints and erythrocyte sedimentation rate (n = 1)); Foot and Ankle Outcome
Score (n = 1); Post-operative nausea and vomiting (n = 1)
hOther units of randomisation: Clinic (n = 1); Family (n = 2); Hospital (n = 1); Household (n = 1); Partner (n = 1); School (n = 1); Village (n = 1); Year group (n = 1);
Paediatric diabetes services (n = 1)
iJustification for no blinding: Not possible or practical due to nature of intervention or trial design (n = 30); Not possible/practical as in practice caused difficulties
for patients (n = 1); Not possible/practical as shown by other similar trials (n = 2); Not possible/practical so cluster randomisation approach used (n = 1); Not
possible – no additional justification given (n = 4); Attempted to blind although were not successful (n = 1); Large sample size means that results are not
compromise (n = 1); Not blinding reflects real practice (n = 2); Test for impact of not blinding post trial (n = 1)
economics (n = 1). Including the Chair, the number of
independents, discussed in 25 publications, ranged
from two to six (most commonly three, n = 17).
Nonindependent members, discussed in three publications,
specified statistical (n = 3) and health economics (n = 2)
Thirty-one listed members without specifying
independence. Represented fields were Patient and Public
Involvement (PPI) (n = 21), clinical (n = 12), statistical
(n = 9), health economics (n = 3) and funder (n = 2).
Three allowed observers at meetings.
Journal manuscripts One publication discussed meeting
frequency (bimonthly meetings (BMJ15)). One stated
yearly reports were circulated (Lancet3) possibly indicating
Seven supplementary protocols provided TSC meeting
information. Four gave the frequency of these, ranging
from monthly to annually. Two were unclear stating
meetings were held periodically. Others reported that meetings
held by teleconference (n = 2) and gave insight to report
contents (n = 1).
Monographs Twenty-five publications (25/144)
discussed meeting frequency or timing. Timings, when
specified, were biyearly (n = 12); yearly (n = 7);
quarterly (n = 2) and as required (n = 1). Three gave
meeting dates and another three gave the total
number of meetings. One specified the length of TSC
meetings as 80–100 min. Four indicated timing of
BMJ British Medical Journal, HTA Health Technology Assessment Monograph series, NA not applicable, NEJM New England Journal of Medicine
first meeting as prior to (n = 2) or at (n = 1) trial
commencement and before recruitment (n = 1)
Journal manuscripts Eleven Lancet and 17 NEJM
publications indicated role or responsibility. No BMJ articles
discussed role. One supplementary appendix reporting
TSCs (1/23 NEJM) gave insight into TSC role.
Design and oversight
Four Lancet publications reported involvement in trial
design, specifically the committee designing the study with
sponsor (2/4), under surveillance of the DMC (1/4), or
supervising the design (1/4). Eleven NEJM publications
reported involvement in design, wherein the role
encompassed overseeing (2/11), being responsible for (3/11) and/
or involvement in (7/11) trial design, with one specifying
that this was independent of the sponsor.
Three Lancet publications reported the TSC
oversee the trial, of which one stated that the TSC
supervised operations. Of the nine NEJM publications
discussing oversight and conduct, five stated that the
TSC oversees the trial (5/9), of which two required
that they oversee conduct specifically (2/9). A
Table 7 TSC name split by journal
Name of TSC
Journal (N reporting TSC) Total
BMJ (N = 6) NEJM (N = 34) Lancet (N = 20) HTA (N = 84) (N = 144)
n n/N% n n/N% n n/N% n n/N% n n/N%
Trial Steering Committee 6 100.0 1 2.9 6 30.0 48 57.1 61 41.7
Steering Committee 0 0.0 18 52.9 12 60.0 12 14.3 42 29.2
Steering Group 0 0.0 0 0.0 0 0.0 14 16.7 14 9.7
Executive Committee 0 0.0 9 26.5 1 5.0 0 0.0 10 6.9
Trial Steering Group 0 0.0 0 0.0 0 0.0 4 4.9 4 2.8
Advisory Committee 0 0.0 2 5.9 0 0.0 0 0.0 2 1.4
Project Steering Group 0 0.0 0 0.0 0 0.0 2 2.4 2 1.4
Study Steering Committee 0 0.0 1 2.9 0 0.0 1 1.2 2 1.4
Clinical Research Organisation 0 0.0 1 2.9 0 0.0 0 0.0 1 0.7
External Protocol Advisory Committee 0 0.0 1 2.9 0 0.0 0 0.0 1 0.7
Monitoring and Steering Committee 0 0.0 1 2.9 0 0.0 0 0.0 1 0.7
Neurology Steering Committee 0 0.0 0 0.0 1 5.0 0 0.0 1 0.7
Scientific Advisory Group 0 0.0 0 0.0 0 0.0 1 1.2 1 0.7
Steering and Advisory Group 0 0.0 0 0.0 0 0.0 1 1.2 1 0.7
Trial Advisory Group 0 0.0 0 0.0 0 0.0 1 1.2 1 0.7
Note: Tabled sorted by total column. BMJ British Medical Journal, HTA Health Technology Assessment Monograph series, NEJM New England Journal of Medicine
(N = 144)
BMJ British Medical Journal, HTA Health Technology Assessment Monograph series, IQR interquartile range, NEJM New England Journal of Medicine, PPI Patient
and Public Involvement, SD standard deviation, TSC Trial Steering Committee
further four stated that the TSC was responsible for
study conduct (4/9).
One supplementary appendix reporting TSCs (1/32, 1/9
Lancet) indicated operational oversight role, specifically:
these stated the TSC had full access to data (3/5), one
supervised the analysis (1/5) and three interpreted the
results (one stating that this was done independently).
‘The Steering Committee was responsible for
overseeing the scientific and operational aspect of the
Thirteen protocols discussed a role in oversight and
trial design: the role encompassed monitoring (n = 5)
and oversight of various aspects of the study (n = 5). The
TSC had a responsibility or participated in trial conduct
(n = 8) and design (n = 5). One stated that the TSC was
Two Lancet publications reported a decision-making
role, stating that the TSC could decide on study
continuation. While no NEJM main papers reported the
decisionmaking role, nine protocols did. Five explicitly defined the
TSC as the decision-making body, the remaining four
opted to provide examples of TSC decisions, such as
altering sample size (n = 2), patient withdrawals (n = 1) and
trial stopping (n = 1).
Contribution to trial documentation, data and
Seven Lancet publications involvement in trial
documentation, stating that the TSC wrote or contributed to
the final report (3/7), made the decision to publish (2/7),
or both (1/7). The TSC coordinated and resolved doubts
in interpretation in the protocol in another. Analysis and
data involvement was reported in five studies, three of
‘The (TSC) vouched for the completion and accuracy
of the data gathering and analysis’. (Lancet6)
Seven NEJM publications reported TSC involvement in
trial documentation, in contributing to writing the
manuscript (4/7) and developing the protocol (3/7), of which
one developed this with the sponsor. Four reported TSC
involvement in trial data, specifically the TSC had full
access to data (1/4) and was involved with data collection
(1/4); interpretation (1/4) and analysis (1/4). In seven, the
committee made the decision to publish, one stated that
the TSC vouches for integrity and completeness of the
data and six stated:
‘The (TSC) vouches for the accuracy and
completeness of the data and the analysis and the
fidelity of the study to the protocol’.
One supplementary appendix reporting TSCs (1/32,
1/23 NEJM) gave insight into role. Fifteen protocols
discussed TSC input into trial documentation, data
and analysis. The TSC was reported to have an input
in publications (n = 13), the protocol (n = 7) and side
studies (n = 4).
No publications specified communication between
TSC and other committees.
One appendix reporting TSCs (1/32) discussed
‘(the DMC) made recommendations to the Steering
Committee regarding endpoint analysis or potential
safety concerns’. (Lancet49)
Eight protocols discussed the TSC communicating with
the DMC (n = 7) and a Critical Event Committee (n = 1).
Monograph Forty monographs described role.
Design and oversight
Twenty-seven monographs described an oversight role,
generally (11/27) or, more specifically, overseeing progress
towards interim and overall objectives (8/27) or study
progress as a whole (8/27). Three stated independent
oversight and two that his was on behalf of the sponsor.
Generic definitions of TSC monitoring were provided
in nine monographs. This was done in accordance
with the MRC guidelines (n = 6), Good Clinical
Practice (n = 1) and in two:
‘The (TSC) ensured that the rights, safety and
wellbeing of the trial participants were the most important
considerations and prevailed over the interests of
science and society’.
Role in decision-making was reported in seven
monographs. Examples were about how the study is run (n = 2);
premature closing (n = 5); and how pilot data will inform
the main trial (n = 2).
Contribution to trial documentation, data and
Twelve had the TSC review trial specific
documentation. Specifically, the statistical analysis plan (n = 8) and
protocol (n = 5).
Ten stated that the TSC review external information
and five had authority over the publication strategy. One
had the TSC approve further analysis and one approved
The committee received recommendations from the
DMC in six monographs, informed funders on trial
progress in three, advised funders in one and liaised
between the DMC and the Trial Management Group
(TMG) in another. One stated that TSC responsibility in
resolving disputes between PIs and another had the
DMC as a subgroup of the TSC.
Journal manuscripts TSC activity having impact on
trial design, conduct and analysis was reported in 12
publications (3 BMJ; 7 Lancet; 2 NEJM) with a total 14
examples reported (4 BMJ; 8 Lancet; 2 NEJM). No
activities were reported in supplementary protocols.
Twelve (12/14; 3/4 BMJ; 7/8 Lancet; 2/2 NEJM)
publications reported TSC activity impacting trial design.
Reported activities varied within journal.
The BMJ reported TSC involvement changing the
sample size (n = 2) and primary outcome (n = 1):
‘Before the start of recruitment and data collection,
we changed the primary outcome to the reported quit
attempt measure, which is predictive of eventual
cessation. This followed expert advice from the Trial
Steering Committee on the basis of smoking cessation
research and approval from the Data Monitoring
All seven Lancet decisions regarded early stopping.
In five, the TSC decided to stop recruitment, of
which three reported that this decision was based on
DMC recommendations. Others reported the TSC
deciding to close recruitment to a trial arm (n = 1) and
make the decision to continue recruitment following
an interim analysis (n = 1):
‘Without revealing any results, the DSMB
recommended to the Executive Committee and
sponsor that the trial continue to the original
pre-planned sample size. The basis for this
recommendation was that, because of the rapid
enrolment at the time of the interim analysis, there
was insufficient 90-day data to assess the secondary
endpoints, although there were no safety concerns.
The Executive Committee and sponsor accepted the
DSMB recommendation to continue enrolment, but
remained masked to all study results’. (Lancet36)
Within the NEJM publications reporting TSC activity
relating to trial design (n = 2), the committee established
when patients could have their dose tapered (NEJM42)
and when crossover could be permitted:
‘The independent Data and Safety Monitoring
Committee and Study Steering Committee
concluded that both progression-free survival and
overall survival were significantly longer in the
trametinib group than in the chemotherapy group
and that immediate crossover to trametinib should
be permitted’. (NEJM23)
One supplementary appendix reported TSCs (1/32)
publishing the letter of recommendation from the DMC
to the TSC requesting one arm be closed due to accruing
safety data (NEJM38), this was consistent with the main
publication wherein the trial was prematurely stopped.
No publication reporting TSC activity related to trial
Two (2/14; 1/4 BMJ; 1/8 Lancet) publications reported
TSC activity impacting analysis.
One described the TSC deciding to write a new SAP
(BMJ3) Another reported the TSC determining
exclusions from analysis and imputations for deaths or drop
Monographs Thirty-seven monographs reported 60
examples of TSC activity.
Thirty-four examples of TSC activity impacting trial
design was reported in 23 monographs.
Activities included the TSC changing the entry criteria
(n = 7); endpoints or outcomes (n = 7); sample size (n = 2);
and randomisation ratio (n = 1). Another reported the
TSC closing a treatment arm (n = 1). Others reported
TSC impact in defining the study design (n = 6) and
recruitment period (n = 2).
Most significantly, the TSC made the decision to close
the trial in five studies, as in HTA238:
‘In a meeting of the Trial Steering Committee, it was
accepted that it would not be viable to proceed with
the trial and the formal procedure for closure
(including notification of MHRA and MREC) was
initiated in May 2005’. (HTA75)
One monograph discussed the TSC overriding the
recommendations of the DMC to close the trial:
‘Although the DMC recommended continuation of
recruitment into FOOD following their meeting in
2002, the Steering Committee took the decision to
stop recruitment on 31 July 2003’. (HTA88)
Fifteen examples of TSC activity impacting trial
conduct was given in 14 monographs.
Examples of conduct were where the TSC: had input in
determining the data collection process (4/14); considered
consent issues (1/14) and input into safety issues; for
example, such as reviewing death data (1/14) and
determining serious adverse event (SAE) data requirements (3/14).
In three (3/14) the TSCs made the decision to
changing treatment regimens; for example:
‘The project Steering Group determined that (a
prescription) was inappropriate to a pragmatic study
of this kind. It was agreed that the outcome would be
more likely to represent the likely outcome of
introducing TUVP if staff were to manage patients
according to existing norms’. (HTA30)
Others (3/14) changed the recruitment procedure, for
‘On reflection and discussion of these issues, the
research team and the Trial Steering Committee
members felt that some of these issues could have
been addressed (…). They concluded that many of the
problems encountered were a direct consequence of
the changes in research governance and ethical
procedures that prevent members of the research
team approaching patients directly, but instead place
the burden of recruiting patients on busy primary care
Ten examples of TSC activity impacting analysis was
given in ten monographs.
The TSC impacted the analysis plan in seven
monographs (7/10). Examples were: determining variables for
regression model (2/7), defining equivalence limits (1/7),
removing previously planned subgroup analyses (1/7),
deciding on the analysis approach to be used, e.g.
intention-to-treat (2/7) or suggesting additional analysis:
‘Finally, at the request of the TSC, a further
exploratory analysis to examine the interactive effect
of age on the effectiveness of MRI compared with no
MRI was conducted’. (HTA111)
Other activities were the TSC determining protocol
violations (1/10) and making the decision to unblind the
trial team (2/10), for example:
‘The identification of treatments was established by code
break in the presence of the Chief Investigator, Trial
Statistician and Trial Coordinator on 20 March 2007 by
agreement with the TSC and DMEC’. (HTA104)
The extent of the adoption of a TSC, the committee with
a majority of independent members to whom the DMC
make their recommendations, for trial oversight outside
of the UK is unknown. Within the UK the establishment
of a TSC is required by a number of major public
funders yet, despite this, there is an absence of reporting
standards regarding their constitution, activities and
impact on trial conduct.
This paper aimed to provide the first review of
reporting of TSC activity by reviewing published academic
literature from within and outside the UK. Determining
the role and contribution of this executive oversight
committee was limited by a lack of reporting and, in
particular, clear indication of whether this committee
included a majority of, or even any, independent members.
It was often unclear whether the TSC being referenced
was in fact the TSC or the TMG, the committee with
heavy intellectual and practical investment in governing
the day-to-day running of the trial. In trials where no
major decisions need to be made, this may seem
unimportant. In trials where DMC recommendations are
not actioned then it is of increasing importance to
understand the extent of the vested interests of the
committee considering those recommendations. In the
cohort reported here one such example was noted
where the DMC recommended trial continuation but
the TSC decided to close the trial. Arguably, this may
be more concerning if this was the other way around;
however, poor reporting standards will obscure this
When interpreting these results, it is important to
consider the limitations which include a restriction of
the cohort to the top medical journals and the NIHR
HTA Monograph series. While this has the advantage
publishing international trials, it may also be argued that
these are of higher quality. The poor standards observed
within this cohort, therefore, may be lower elsewhere.
The timeframe of this cohort also prevented
consideration of changes over time; however, given the absence
of attention received to this important role and its
reporting standards this is unlikely. As previously
discussed, the extent of the adoption of this oversight
committee structure is not known for trials outside of
UK and little is known about industry-funded and
For TSCs to be accepted as good practice globally, it is
important that the benefits and impact of such a
committee are reported. This paper has highlighted the need
to improve reporting of TSCs and, in particular, clarify
the independence, or otherwise, of its members. Despite
the academic literature search being conducted in 2012
there has been no advancement in reporting guidelines
in this area and the situation remains unchanged.
Current reporting recommendations for DMCs [
could be used as a starting point with focus on decisions
made by the TSC.
One challenge of writing a report of a clinical trial is
including pertinent information within word limits set
by journals. It is often a balance of what can be left out
without jeopardising quality. However, clarity of
reporting on decision-making processes would seem essential
given the potential for bias. With the availability of
supplementary material, researchers must make this
information publicly accessible. This would greatly aid the
transparency of clinical trials and allow understanding of
stakeholder involvement in decisions made.
This cohort examination provides the first examination
of reporting practice of Trial Steering Committee
involvement in randomised controlled trials. A lack of
reporting standards has been identified, resultantly
understanding the benefits and impact of the TSC role
using the academic literature is challenging. Developing
reporting guidelines is essential to aid determining the
role and contribution of this executive oversight
committee. This would improve reporting standards, which
would greatly aid the transparency of clinical trials and
allow understanding of stakeholder involvement in
Additional file 1: Table S1. Project identification numbers of included
articles. Table listing all trials in cohort. (DOCX 48 kb)
BMJ: British Medical Journal; DMC: Data Monitoring Committee; NEJM: New
England Journal of Medicine; NICE: National Institute for Health and Care
Excellence; NIHR HTA: National Institute for Health Research Health
Technology Assessment; TMG: Trial Management Group; TSC: Trial Steering
Committee; UK: United Kingdom
This work was supported by the Medical Research Council Hubs for Trials
Methodology Research Network.
Availability of data and materials
The datasets used and/or analysed during the current study are available
from the corresponding author on reasonable request.
EJC participated in the study design, drafted the manuscript, conducted the
academic literature search, developed the Data Extraction Form and
extracted and analysed the data. CG participated in the study design,
developed the Data Extraction Form and analysed the data. BA extracted the
data. NLH, AL, SL, JN and MRS participated in the study design. All authors
reviewed and approved the final manuscript.
Ethics approval and consent to participate
Not applicable, not a study involving human participants, human data, or
Consent for publication
Not applicable, no individual personal data.
The authors declare that they have no competing interests.
Springer Nature remains neutral with regard to jurisdictional claims in published
maps and institutional affiliations.
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