This poster presents a summary of research conducted to assess consistency of data reporting between clinical trials listed on clinicaltrials.gov and corresponding peer-reviewed medical publications for oncology drugs approved by the FDA between 2014 and 2016.

1. Audio
Summary
Scan
for poster
CONSISTENCY OF CLINICAL DATA
REPORTING BETWEEN CLINICALTRIALS.GOV
AND PUBLICATIONS
Michelle Rebello, Aparna Nori, Sudha Korwar, Urvashi Nikte, Kushal Banerjee, and Namita Bose
Cactus Communications, Mumbai, India
14th
Annual Meeting of ISMPP (April 30–May 2, 2018), National Harbor, MD, USA
#6
Introduction
& Objective
Abstract Methods Results Conclusions
& Limitations
Acknowledgments References

2. CONSISTENCY OF CLINICAL
DATA REPORTING BETWEEN
CLINICALTRIALS.GOV
AND PUBLICATIONS
Comparison of efficacy and safety data reporting between clinicaltrials.gov and publications for oncology drugs
2014a
2015a
2016a
Total (%)
Completed Phase II–IV trials on clinicaltrials.gov 14 35 2 51 (100)
Trials with study results posted on clinicaltrials.gov 11 21 1 33/51 (64.7)
Trials with corresponding publications 10 15 0 25/51 (49.0)
Trials with efficacy (primary and secondary) results 22/51b
(43.1)
Trials with safety results 25/51 (49.0)
Efficacy datac
Trials with consistent primary efficacy outcome/s between clinicaltrials.gov and publication 21/22 (95.5)
Trials with consistent secondary efficacy outcomes between clinicaltrials.gov and publication 8/22 (36.4)
Trials used for clinicaltrials.gov/publication data comparisond
18/22 (81.8)
Trials in which primary efficacy data matched 17/18 (94.4)
Safety datac
SAEse
Trials with SAE data posted on clinicaltrials.gov 25/25 (100)
Trials reporting SAE data in corresponding publication 14/25 (56.0)
Trials used for clinicaltrials.gov/publication data comparisond
8/25 (32.0)
Trials in which SAE data matched 5/8 (62.5)
Other AEsf
Trials with AE data posted on clinicaltrials.gov 25/25 (100)
Trials reporting AE data in corresponding publication 19/25 (76.0)
Trials used for clinicaltrials.gov/publication data comparisond
10/25 (40.0)
Trials in which AE data matched 5/10 (50)
a
Year of US FDA-approval for oncology drug
b
Out of 25 registered trials with corresponding publications, 3 were safety trials with no primary efficacy component
c
Completed trials on clinicaltrials.gov (having results posted) which had corresponding publications were used for efficacy (n=22) and safety (n=25) analyses
d
Subset of completed trials in which efficacy and/or safety data could be compared between clinicaltrials.gov and publication based on comparable population and timing
of reporting results in the publication
e
SAEs include AEs that result in death, require either inpatient hospitalization or the prolongation of hospitalization, are life-threatening, result in a persistent or significant
disability/incapacity or result in a congenital anomaly/birth defect
f
Includes all AEs other than SAEs
AEs, adverse events; SAE, serious adverse events
Objective
Reporting of results on clinical trial registries and development of medical
publications are handled by discrete functions within the biopharmaceutical industry.
We assessed consistency of reporting, given the importance of providing accurate
clinical trial data to both clinicians and patients.
Research design and methods
We compared results of completed Phase II–IV trials on clinicaltrials.gov with
corresponding publications for US FDA-approved oncology drugs (2014–2016).
Results
Of 51 completed trials, 64.7% posted results on clinicaltrials.gov and 49.0% also had
corresponding publications (Table). Primary and secondary efficacy outcomes were
consistent between clinicaltrials.gov and publications in 95.5% and 36.4% trials,
respectively, with primary efficacy data matching in 94.4% trials. All examined trials
reported serious adverse events (SAEs) and other AEs on clinicaltrials.gov versus
56.0% and 76.0%, respectively, in publications. SAE and AE data matched in
62.5% and 50.0% trials, respectively, between clinicaltrials.gov and corresponding
publications.
Conclusions
There is a need for greater concordance in reporting secondary efficacy outcomes
and safety data between clinical trial registries and medical publications.
Introduction
& Objective
Abstract Methods Results Conclusions
& Limitations
Acknowledgments References

3. CONSISTENCY OF CLINICAL
DATA REPORTING BETWEEN
CLINICALTRIALS.GOV
AND PUBLICATIONS
Introduction
• The United States Food and Drug Administration (US FDA) and other regulatory
bodies, such as the European Medicines Agency and World Health Organization,
mandate registration of clinical trials and submission of results within 1 year of
study completion1–3
• Regulatory bodies also recommend that the main findings be submitted for
publication in a peer-reviewed journal within 1 year of study completion3,4
• The validity of clinical trial registries and medical publications as data sources is
integral to the accurate and balanced reporting of clinical trial data; however,
data reporting is inconsistent between clinical trial registries and published data5,6
• To better understand the extent of incongruities, we compared data reported
in a clinical trial registry and corresponding medical publications for recent
FDA-approved drugs within the oncology therapy area
Objective
• To assess consistency of data reporting between clinical trials listed on
clinicaltrials.gov and corresponding peer-reviewed medical publications for
oncology drugs approved by the FDA between 2014 and 2016
Introduction
& Objective
Abstract Methods Results Conclusions
& Limitations
Acknowledgments References

4. CONSISTENCY OF CLINICAL
DATA REPORTING BETWEEN
CLINICALTRIALS.GOV
AND PUBLICATIONS
Data extraction and comparison
clinicaltrials.gov
Publication
Clinical
trials.gov
Were the same primary and secondary
efficacy outcome measures reported?
Did primary efficacy data match?*
Were SAEs†
, other AEs‡
, and
discontinuations due to AEs reported?
Did the data for total # (or total #/group) of SAEs, other AEs,
and discontinuations due to AEs match?*
Methods
• Oncology drugs approved by the FDA between January 1, 2014, and December 31,
2016, were identified using the FDA archives7
• Completed Phase II–IV trials for approved drugs were identified on
clinicaltrials.gov
• Of the completed trials, those with results posted on clinicaltrials.gov and
with results published in a peer-reviewed journal were used for further analysis
»» Publications were identified as reported on clinicaltrials.gov or through a
PubMed search using appropriate search strings. The NCT number was used to
match the publication to the registered trial.
*Data were compared in a subset of trials for which (1) data were available in both the registry and publication and (2) time-frame
reported in the publication matched the clinicaltrials.gov entry
† SAEs included AEs that were life-threatening; required either inpatient hospitalization or prolongation of hospitalization; or led to
a congenital anomaly/birth defect, persistent or significant disability/incapacity, or death
‡
Other AEs included AEs other than SAEs
AE, adverse event; SAE, serious adverse event
Introduction
& Objective
Abstract Methods Results Conclusions
& Limitations
Acknowledgments References

5. CONSISTENCY OF CLINICAL
DATA REPORTING BETWEEN
CLINICALTRIALS.GOV
AND PUBLICATIONS
Phase II, 52%
(n=13)
Phase III, 40%
(n=10)
Phase IV, 8%
(n=2)
Primary study
completion date
Publication
date
17.6 (±14.9) months
*Of 25 registered trials with corresponding publications, 3 were safety trials with no primary efficacy component
FDA, Food and Drug Administration
Completed Phase II–IV
trials for FDA-approved
oncology drugs, N=51
Trials with
results posted on
clinicaltrials.gov
(65%; n=33)
Trials with
corresponding
peer-reviewed
publications
(49%; n=25)
Trials used for efficacy
analysis, n=22*
Trials used for safety
analysis, n=25
2014, n=14
2015, n=35
2016, n=20
2014, n=11
2015, n=21
2016, n=10
2014, n=10
2015, n=15
2016, n=00
Results
• A total of 29 oncology drugs were approved by the FDA between 2014 and 2016
• Of these, 20 drugs were associated with 51 completed Phase II–IV trials, and
half of the trials had results posted on clinicaltrials.gov as well as corresponding
peer-reviewed publications
• More than half of the completed trials with results posted on clinicaltrials.gov
and corresponding publications were Phase II trials
• Average time from study completion to publication was nearly 1.5 years
Scan for
list of drugs
Introduction
& Objective
Abstract Methods Results Conclusions
& Limitations
Acknowledgments References
q
Data
selection
Efficacy
outcomes
Safety
outcomes

6. CONSISTENCY OF CLINICAL
DATA REPORTING BETWEEN
CLINICALTRIALS.GOV
AND PUBLICATIONS
95.5% (n=21)
4.5%
(n=1)
Consistent
Primary
efficacy outcomes
Secondary
efficacy outcomes
Inconsistent
36.4% (n=8)63.6% (n=14)
1 trial
Outcome changed to a
more clinically relevant
outcome in publication
7 trials
# of outcomes on
clinicaltrials.gov
> in publication
6 trials
# of outcomes on
clinicaltrials.gov
< in publication
Data matched
94.4%
(n=17)
Trials used
for comparison
81.8%
(n=18)
Data did
not match
5.5%
(n=1)
Trials not
used for
comparison
18.2%
(n=4)*
Were the same primary and secondary efficacy outcome measures
reported?
• Primary efficacy outcomes were more consistently reported than secondary
efficacy outcomes between clinicaltrials.gov and corresponding publications
(efficacy analysis; n=22 trials)
Did primary efficacy data match?
match?
• For all but 1 trial, primary efficacy data reported on clinicaltrials.gov matched those
in corresponding publications
*4 out of 22 trials were not used for data comparison because of mismatched time-frames between clinicaltrials.gov entry
and publication
Introduction
& Objective
Abstract Methods Results Conclusions
& Limitations
Acknowledgments References
q
Data
selection
Efficacy
outcomes
Safety
outcomes

7. CONSISTENCY OF CLINICAL
DATA REPORTING BETWEEN
CLINICALTRIALS.GOV
AND PUBLICATIONS
• SAEs and other AEs were reported for all trials on clinicaltrials.gov versus
56% (n=14) and 76% (n=19) of trials, respectively, in publications
• Discontinuations due to AEs were reported more frequently in publications
(92%; n=23) than on clinicaltrials.gov (80%; n=20)
Were SAEs, other AEs, and discontinuations due to AEs reported?
*In 4 trials, only treatment-related SAEs were reported in the publication
AE, adverse event; SAE, serious adverse event
• A total of 25 trials were used in the safety analysis
Percentage of trials (%)
0 10 20 30 40 50 60 70 80 90 100
56% (n=14)*
76% (n=19)
92% (n=23)
Publication clinicaltrials.gov
100% (n=25)
100% (n=25)
80% (n=20)
SAEs reported
Other AEs reported
Discontinuations
due to AEs reported
Introduction
& Objective
Abstract Methods Results Conclusions
& Limitations
Acknowledgments References
q
Data
selection
Efficacy
outcomes
Safety
outcomes 1/2

8. CONSISTENCY OF CLINICAL
DATA REPORTING BETWEEN
CLINICALTRIALS.GOV
AND PUBLICATIONS
MatchedDid not match
Total # of SAEs
Total # of other AEs
Total # of discontinuations
due to AEs
62.5% (n=5)37.5% (n=3)
50% (n=5)50% (n=5)
72.7% (n=8)27.3% (n=3)
32%
(n=8)
68%
(n=17)
44%
(n=11)
56%
(n=14)
SAEs
Discontinuations
due to AEs
Trials used for publication/registry data comparison
Trials not used for publication/registry data comparison
40%
(n=10)
60%
(n=15)
Other AEs
• For two-thirds of the trials analyzed, the total number of SAEs reported on
clinicaltrials.gov matched that in corresponding publications
• For half of the trials analyzed, the total number of other AEs reported on
clinicaltrials.gov matched that in corresponding publications
• For almost three-quarters of the trials analyzed, the total number of
discontinuations due to AEs reported on clinicaltrials.gov matched that in
corresponding publications
Did safety data match?
• Comparison of safety data was possible only for a small subset of trials that:
»» had safety data included in both the registry and publication, and
»» shared the same time-frame for the clinicaltrials.gov entry and the publication
AE, adverse event; SAE, serious adverse event
Introduction
& Objective
Abstract Methods Results Conclusions
& Limitations
Acknowledgments References
q
Data
selection
Efficacy
outcomes
Safety
outcomes 2/2

9. CONSISTENCY OF CLINICAL
DATA REPORTING BETWEEN
CLINICALTRIALS.GOV
AND PUBLICATIONS
Conclusions
• Primary efficacy outcome measures and primary efficacy outcome data were
highly consistent between clinicaltrials.gov and corresponding publications
• Reporting of secondary efficacy outcome measures was less consistent,
with two-thirds of publications having greater or fewer outcomes than those
prespecified in the registry
• Safety data reporting was highly varied between clinicaltrials.gov and
corresponding publications, with mismatches in safety data observed in more than
a third of the trials analyzed
• Overall, greater concordance is needed with respect to reporting secondary
efficacy outcome measures and safety data between clinicaltrials.gov and
medical publications
Limitations
• This study did not include a comparison of secondary efficacy data between
clinicaltrials.gov and corresponding publications because of the large number of
secondary endpoints for each study
• Safety data comparison was possible in only a small subset of trials for which
safety results were available in both data sources and the time-frame of reporting
results matched between the registry and the corresponding publication
Introduction
& Objective
Abstract Methods Results Conclusions
& Limitations
Acknowledgments References

10. CONSISTENCY OF CLINICAL
DATA REPORTING BETWEEN
CLINICALTRIALS.GOV
AND PUBLICATIONS
USA | UK | Japan | India | South Korea | China | Singapore
Acknowledgments
• Poster design, layout, and production support was provided by Dirk Eggermont
of Cactus Communications
• Editorial assistance was provided by Maribeth Bogush, PhD
• This study was funded by Cactus Communications
Introduction
& Objective
Abstract Methods Results Conclusions
& Limitations
Acknowledgments References

11. CONSISTENCY OF CLINICAL
DATA REPORTING BETWEEN
CLINICALTRIALS.GOV
AND PUBLICATIONS
References
1. Federal Register. Clinical Trials Registration and Results Information
Submission. 2016
2. European Medicines Agency. Posting of Clinical Trial Summary Results in
European Clinical Trials Database (EudraCT) to Become Mandatory for Sponsors
as of 21 July 2014. 2014
3. World Health Organization. WHO Statement on Public Disclosure of
Clinical Trial Results. 2015
4. General Assembly of the World Medical Association. J Am Coll Dent.
2014;8(13):14–8
5. JE Becker et al. JAMA. 2014;311(10):1063–5
6. E Tang et al. BMC Med. 2015;13(1):189
7. US Food and Drug Administration. New Drugs at FDA:
CDER’s New Molecular Entities and New Therapeutic Biological Products. 2018
Introduction
& Objective
Abstract Methods Results Conclusions
& Limitations
Acknowledgments References