Transcript Open slide - CTN Dissemination Library

Monitoring the Progress of Clinical Trials in a Network Setting:
Experience from the National Drug Abuse Treatment Clinical Trials Network
P. VanVeldhuisen1, C. Allen1, A. Wahle1, L. Lu1, C. Cushing2, P. Wakim2, B. Tai2
1NIDA
Data and Statistics Center 2, The EMMES Corporation, Rockville, MD; 2NIDA Center for the Clinical Trials Network, Bethesda, MD
Abstract
Audience
The National Drug Abuse Treatment Clinical Trials Network (CTN), established by the
National Institute on Drug Abuse (NIDA), has developed a comprehensive set of webbased standardized Trial Progress Reports (TPR) to use as a management tool to
effectively monitor the progress of on-going clinical trials in real-time. These reports
track the progress of each protocol within the CTN from the date of first randomization
to final closeout and publication of main results. The content includes areas from all
aspects of the clinical trials: recruitment, retention, availability of primary outcome,
treatment exposure (i.e., the number of medication or placebo doses actually taken, or
psychosocial therapy sessions actually attended, divided by the corresponding number
that a participant is expected to take or attend), quality assurance, and regulatory.
Most of the reports in the TPR are updated daily and all reports are web-based and are
available on a secure website to provide real-time access to critical protocol
information. The TPR provides both a big-picture view of the NIDA CTN protocols and
a very detailed view to meet the needs of the varied audience, which include:
NIDA as the Sponsor and the
Executive Committee as the CTN Governance Body
NIDA’s Center for the Clinical Trials Network and the CTN Executive Committee use the
TPR to assess the overall progress of multiple on-going protocols. Example
presentations below include protocol-specific monthly recruitment in the CTN and
overall protocol performance statistics. Protocol performance statistics show colorcoded boxes across various monitored areas, where green denotes good performance,
yellow where problem areas are identified, and red where poor performance is noted
and remedial actions required.
Lead Investigative Team as the Study Leaders
The Lead Investigative Team of the clinical trial uses the TPR to monitor overall
progress of the protocol and to identify areas of concern on an individual site level.
Example presentations below include expected number of randomizations compared
with actual, and site-level performance with green, yellow and red color designations.
Investigators and staff at participating sites use the TPR to monitor their individual
site’s performance against other sites. Example presentations below include
recruitment, treatment exposure, primary outcome availability, and long-term follow-up.
Expected vs. Actual Randomizations, By CTP
Expected vs. Actual Randomizations, Overall
CTP1
CTP2
CTP3
CTP4
CTP5
CTP6
CTP7
CTP8
CTP9
CTP10
Number of Participants Randomized on Active Trials
2010
Protocol
 The sponsor and study leadership to assess the overall progress of multiple
on-going protocols.
 The protocol lead teams to monitor their respective protocols in order to
identify areas of concern on an individual site level.
 The investigators and staff at each participating community treatment provider
(CTP) within a protocol to monitor their individual site’s performance against
other sites.
Metrics have been developed for key protocol components to provide feedback at a
glance on the progress of the protocols. These metrics have been assigned colorcodes, where green denotes good performance, yellow where problem areas are
identified, and red where poor performance is noted and remedial actions required.
Community Treatment Providers (CTPs)
as the Participating Sites
CTN-9996
CTN-9997
CTN-9998
CTN-9999
Total
Jun
Jul
0
10
15
0
25
8
32
20
0
60
Aug Sep
9
37
16
0
62
13
35
12
0
60
2011
Oct
3
38
15
12
68
Nov Dec
13
33
20
53
119
Jan
Feb
Mar
Apr
10
33
16
39
98
14
33
16
67
130
12
38
25
76
151
15
28
32
38
113
7
28
21
46
102
Month to
date
8
20
30
70
128
Last
Protocol Total
12
months
112
112
365
365
238
321
401
401
1116
1199
Trial Performance (Flags and Triggers) for Active Protocol
Recruitment
Missing
Forms
Audits
Regulatory
Availability of
Primary
Outcome Data
Treatment
Exposure
Follow-up
Visits
114%
92%
102%
112%
0.1%
0.0%
0.4%
0.3%
0.4%
0.3%
0.3%
0.1%
None
None
None
None
89%
65%
91%
82%
78%
69%
94%
59%
68%
71%
75%
84%
CTP
CTN-9996
CTN-9997
CTN-9998
CTN-9999
Expected and Actual Randomizations, Overall and by CTP
The TPR has allowed the NIDA CTN leadership and protocol teams to monitor and
intervene in the critical aspects of recruitment, retention, data quality, and treatment
implementation to improve upon the overall quality of the research being conducted.
Date CTP
Opened for
Enrollment
Date of 1st
Randomization
Expected
Randomizations
to Date **
Actual
Randomizations,
Cumulative
Actual/
Expected
(%)
Actual/
Proposed
(%)
Expected or
Actual Date of
Last
Randomization
Expected
or Actual
Date of
Last Follow
up ***
CTP 1
50
06/09/2010
06/16/2010
30
30
80%
48%
07/02/2011
05/11/2012
CTP 2
50
07/01/2010
07/08/2010
27
27
85%
46%
07/24/2011
06/02/2012
CTP
Explanation of Color Code for Performance Tables
Green
Dash Board View
Proposed
Randomization*
Yellow
Red
CTP 3
50
06/29/2010
07/14/2010
26
26
119%
62%
07/30/2011
06/08/2012
Recruitment
Randomized is more than 80% of
expected.
Randomized is between 60% and
80% of expected.
Randomized is below 60% of
expected.
CTP 4
50
06/29/2010
07/06/2010
27
27
70%
38%
07/22/2011
05/31/2012
Data Quality: Audits
Error rate is less than 0.5%.
Error rate is between 0.5% and 1%.
Error rate is greater than 1%.
CTP 5
50
06/28/2010
07/29/2010
24
24
71%
34%
08/14/2011
06/23/2012
Data Quality: Missing
Forms
Percent of missing forms overdue (>
30 days) is less than 0.5%.
Percent of missing forms overdue (>
30 days) is between 0.5% and 1%.
Percent of missing forms overdue
(> 30 days) is greater than 1%.
CTP 6
50
06/11/2010
06/14/2010
30
30
107%
64%
06/30/2011
05/09/2012
CTP 7
50
06/28/2010
07/19/2010
25
25
96%
48%
08/04/2011
06/12/2012
Regulatory
All have up-to-date IRB and FWA
approval.
One or more active sites have IRB
or FWA approval expiring within the
next 30 days.
One or more active sites do not
have up-to-date IRB or FWA
approval.
CTP 8
50
06/29/2010
08/03/2010
23
23
91%
42%
08/19/2011
06/28/2012
CTP 9
50
06/28/2010
07/07/2010
27
27
104%
56%
07/23/2011
06/01/2012
Availability of Primary
Outcome Data
Percent of primary outcome
measures with values is more than
80%.
Percent of primary outcome
measures with values is between
60% and 80%.
Percent of primary outcome
measures with values is below
60%.
CTP 10
50
06/11/2010
06/17/2010
29
29
93%
54%
07/03/2011
05/12/2012
Overall
500
06/09/2010
06/14/2010
268
246
92%
49%
08/19/2011
06/28/2012
Treatment Exposure
Average proportion of treatment
sessions attended is more than 80%.
Average proportion of treatment
sessions attended is between 60%
and 80%.
Average proportion of treatment
sessions attended is below 60%.
Follow-up Visits
Average proportion of follow-up visits
attended is more than 70%.
Average proportion of follow-up
visits attended is between 50% and
70%.
Average proportion of follow-up
visits attended is below 50%.
* Proposed Randomization=final target number of randomizations per CTP based on the sample size N. These numbers will not change in successive Trial Progress
Reports.
** Expected Randomization to Date=number of randomizations expected at this point in time, based on the randomization rate specified in the protocol. These numbers will
change from one Trial Progress Report to the next.
*** Expected date=Date of last randomization + upper limit of time window for last follow-up visit.
Availability of Primary Outcome Measure
CTP
CTP 1
CTP 2
CTP 3
CTP 4
CTP 5
CTP 6
CTP 7
CTP 8
CTP 9
CTP 10
Overall
CTN-9996
CTN-9997
CTN-9998
CTN-9999
Key Features of TPR
• Timing
• Updated daily to allow real-time information on status of protocols
• Format of tables
• Consistent format and performance criteria to allow comparisons
across protocols
• Individual reports and consolidated reports available from dash board
• All in pdf format
• No treatment-specific or outcome data (beyond availability) provided
Recruitment
Missing
Forms
Audits
Regulatory
Availability of
Primary Outcome
Data
Treatment
Exposure
Follow-up
Visits
CTP 1
81%
0.1%
0.13%
None
64%
44%
100%
CTP 2
85%
0.0%
0.08%
None
62%
74%
80%
CTP 3
119%
0.0%
0.01%
None
68%
75%
88%
CTP 4
70%
0.0%
0.02%
None
3%
77%
50%
CTP 5
71%
0.0%
0.04%
None
71%
58%
50%
CTP 6
107%
0.0%
0.01%
None
68^
79%
67%
CTP 7
96%
0.0%
0.01%
None
76%
77%
88%
CTP 8
91%
0.0%
0.06%
None
41%
60%
29%
CTP 9
104%
0.0%
0.01%
None
75%
87%
78%
CTP 10
93%
0.0%
0.05%
None
55%
51%
67%
Overall
92%
0.0%
0.03%
None
65%
69%
71%
CTP
CTP 1
CTP 2
CTP 3
CTP 4
CTP 5
CTP 6
CTP 7
CTP 8
CTP 9
CTP 10
Overall
Actual Number
of Treatments
195
333
485
285
207
446
316
287
506
292
3352
Total
Number of
Treatments
Expected
440
448
644
368
356
564
412
476
580
568
4856
Percentage of Expected
Outcome Measures
Available
64%
62%
68%
73%
71%
68%
76%
41%
75%
55%
65%
Primary Outcome Measures
Available
300
264
401
251
230
414
335
161
412
307
3075
Attendance at Long-Term Follow-Up Visits
Treatment Exposure
CTP
Flags and Triggers: Overall and by CTP
Expected Primary
Outcome Measures
472
428
590
344
324
612
442
392
550
556
4710
Percentage
of Expected
Treatments
Completed
44%
74%
75%
77%
58%
79%
77%
60%
87%
51%
69%
CTP
CTP 1
CTP 2
CTP 3
CTP 4
CTP 5
CTP 6
CTP 7
CTP 8
CTP 9
CTP 10
Overall
Attendance at
Long-term Follow-up Visit
6/6 (100%)
4/5 (80%)
7/8 (88%)
2/4 (50%)
2/4 (50%)
9/12 (75%)
7/8 (88%)
2/7 (29%)
7/9 (78%)
7/9 (78%)
53/72 (74%)
Acknowledgement
This research was supported by the National Institute on Drug Abuse, National Drug
Abuse Treatment Clinical Trials Network, National Institutes of Health, through Contract
No. HHSN271200900034C.