Effective Presentation of Study Results

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Effective Presentation of Study Results
How are RCTs presented in abstracts
publications? and Some things to consider in your
own presentations
NCIC CTG New Investigators Course October
2009 Christopher Booth MD FRCPC Queens
University Cancer Research Institute
The Cancer Research Institute at Queens
University Division of Cancer Care and
Epidemiology
2
Outline Part I

• How are RCTs presented in abstracts
  publications?
• Evolution of endpoints and perception of benefit
  in oncology RCTs over time
• What results are clinically meaningful?
• RCTs closed early for benefit
• How are RCTs presented at conferences?

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University Division of Cancer Care and
Epidemiology
3
Outline Part II

• Issues to consider when presenting your study
  results
• Audience
• Preparation
• Key messages
• Fancy PowerPoint
• Summary

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University Division of Cancer Care and
Epidemiology
4
Part I How are RCTs presented in abstracts
publications?
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University Division of Cancer Care and
Epidemiology
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1. How have endpoints and perception of benefit
evolved in oncology RCTs?
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Study Design

• Overview of all RCTs systemic therapy in breast,
  NSCLC, colorectal cancer
• 1975-2004
• 6 major journals JCO, Cancer Treatment Reports,
  JNCI, NEJM, Lancet, JAMA
• Data abstraction using standardized forms and
  methodology

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University Division of Cancer Care and
Epidemiology
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Temporal Trends
1975-84 1985-94 1995-2004 P value (trend)
Total RCTs 47 (15) 107 (33) 167 (52) lt0.0001

Breast RCTs 19 (40) 53 (50) 81 (49) 0.475
NSCLC RCTs 23 (49) 29 (27) 39 (23) 0.002
CRC RCTs 5 (11) 25 (23) 47 (28) 0.017
321 RCTS over three decades involving gt170 000
patients
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University Division of Cancer Care and
Epidemiology
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Study Participants
1975-84 1985-94 1995-04 P (trend)
International 26 28 52 lt0.0001
Co-op group 28 56 43 0.661

Sample size 100 249 446 lt0.0001
Accrual time 30 mo 41 mo 33 mo 0.93
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University Division of Cancer Care and
Epidemiology
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Statistics
1975-84 1985-94 1995-04 P (trend)
1º endpoint
Time to event 39 72 78 lt0.0001
RR 54 25 14 lt0.0001
ITT analysis
Any 70 87 93 lt0.0001
33 of RCTs in 1995-2004 did not clearly identify
primary endpoint
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University Division of Cancer Care and
Epidemiology
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Sponsorship
1975-84 1985-94 1995-04 P (trend)
Government 60 62 31 lt0.0001
Industry 4 23 57 lt0.0001
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University Division of Cancer Care and
Epidemiology
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Effect Size and Conclusions
1975-1984 1985-1994 1995-2004
Median HR (95CI) 1.4 (1.0-2.3) 1.2 (1.0-2.4) 1.2 (1.1-1.3)
Plt0.05 for primary EP 23 30 42
Strong endorsement 31 39 49
1. Effect size stable over time 2. Modern RCTs
more likely to have plt0.05 3. Modern authors more
likely to call their trial positive
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University Division of Cancer Care and
Epidemiology
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The Cancer Research Institute at Queens
University Division of Cancer Care and
Epidemiology
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Key Findings

1. Increase in number and size of RCTs
2. More international trials, faster accrual
3. Shift in primary endpoint from RR to survival EPs
   
4. Major shift towards for-profit sponsorship
5. Effect size has remained stable over time
6. Authors of modern RCTs more likely to endorse
   experimental arm
7. For-profit sponsorship and plt0.05 are
   independently associated with strong endorsement
   of experimental arm

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University Division of Cancer Care and
Epidemiology
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2. Are these results clinically meaningful?

• Clinically Relevant Endpoints
• Patients define a useful therapy as one that
• increases survival OR
• improves QOL/reduces symptoms of cancer
• Reassuring shift from RR to survival endpoints
• Increasing use and recognition of PROs
  Gemcitabine Pancreas TAX 327 HRPC

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University Division of Cancer Care and
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Clinically Relevant Endpoints

• Current standards for analyzing QOL and symptom
  control need improvement
• 112 RCTs for advanced cancer
• 19 established a priori hypothesis
• 21 defined minimal differences in QOL scores
  that were clinically meaningful
• Increasing use of surrogate endpoints (DFS, PFS)

Joly et al Ann Oncol 2007 Sargent et al JCO 2005
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University Division of Cancer Care and
Epidemiology
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University Division of Cancer Care and
Epidemiology
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Clinically Relevant Endpoints

• Clinical benefit (CB) in trials of pancreas
  cancer
• composite improvement in pain, weight,
  performance status
• CB now widely (mis)used to describe PR/CR/SD
• 71 trials in JCO since 1997
• 28 used patient-centered definition
• 72 referred to objective tumor measurements

Burris et al JCO 1997 Ohorodnyk et al ASCO 2009
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University Division of Cancer Care and
Epidemiology
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(No Transcript)
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3. RCTs Closed Early for Benefit
Korn et al JCO 2009 Sargent JCO 2009
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Korn et al JCO 2008

• 27 NCI co-operative group trials that were closed
  early for benefit
• Of the 18 trials with follow-up available,
  initial magnitudes of benefit were preserved in
  17 (94) trials
• the system is working
• Dan Sargent JCO 2008

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University Division of Cancer Care and
Epidemiology
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Booth, Meyer et al Under Review

• Literature search identified 62 RCTCEB
• Primary endpoint not explicitly stated in 19
• ITT all randomized patients in only 66
• Most trials open to accrual (45/62, 73) at the
  time of closure.
• Formal IA performed in 56 (90) trials
• 75 (42/56) planned and 79 (44/56) reported
  stopping rules.
• Trials on average accrued 73 of the planned
  sample size.
• Follow-up reports for 18 (29) RCTCEB show that
  results and conclusions were maintained.

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4. How are RCTs presented at conferences?
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University Division of Cancer Care and
Epidemiology
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Trial Reporting NFAs

• 138 RCTs published 2000-2004
• 197 corresponding abstracts 1990-2004
• Results were stated or implied to be non-final
  analyses in 86 abstracts (44)
• 124 abstracts (63) discordant with article
• Conclusions substantively different in 17 (10)

Meeting abstracts often include NFAs and are
often discordant with mature publication
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University Division of Cancer Care and
Epidemiology
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Bias in Oncology RCTs

• Publication Bias
• 510 RCTs presented at ASCO 1989-1998
• 26 were not published within 5 years
• 81 of trials with plt0.05 were published compared
  to 68 of trials with pgt0.05
• This should improve with mandatory trial
  registration

Krzyzanowska JAMA 2003
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University Division of Cancer Care and
Epidemiology
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Bias in Oncology RCTs

• Sponsorship Bias
• Multiple studies have demonstrated that RCTs
  sponsored by industry are more likely to be
  positive than non-industry trials
• Reasons are likely complex and multifactorial

Djulbegovic Lancet 2000 Booth JCO 2008 Peppercorn
Cancer 2007
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University Division of Cancer Care and
Epidemiology
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ACS 2008 Statistics
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Part I SUMMARY

• 1. Major changes in cancer treatment/research
  since 1970s
• Patient outcomes have improved
• RCT methodology and reporting are improving
• Trials are larger, complex, stronger
  correlative component
• What constitutes a positive trial has changed
  
• 2. It is critical to keep in patient-centered
  outcomes in focus at every step of the drug
  development pathway
• 3. Be critical in the way you interpret results
  of RCTs in published form and at conferences

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University Division of Cancer Care and
Epidemiology
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Acknowledgements

• Drs. Ralph Meyer and Bill Mackillop
• NCIC Clinical Trials Group
• Queens University Cancer Research Institute
• Kingston, Ontario
• Drs. Ian Tannock and Monika Krzyzanowska
• Princess Margaret Hospital, Toronto, Ontario

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University Division of Cancer Care and
Epidemiology
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Part IIThings to consider when presenting your
own study results
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University Division of Cancer Care and
Epidemiology
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Topics for Discussion

1. Audience
2. Preparation and timing
3. Key messages
4. Fancy PowerPoint (?)
5. Summary
6. Time for discussion

The Cancer Research Institute at Queens
University Division of Cancer Care and
Epidemiology