Clinical trials, data sharing and supplemental materials

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Clinical trials, data sharing and supplemental
materials

• Andrew J. Vickers
• Department of Epidemiology and Biostatistics
• Memorial Sloan-Kettering Cancer Center
• 1.30 2pm. SSP meeting

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Should authors of clinical trials be able to be
submit supplemental materials?
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It should be compulsory
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NY times scan
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Read first para of NYT article
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Overview of talk

• Experiences trying to obtain raw data
• Advantages of making raw data available
• Arguments against data sharing
• A code of conduct for use of raw data
• A final thought will journals step up to the
  plate?

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Typical experiences trying to obtain data from
medical trials

• Needed data from the control arm of a trial to
  help design a study
• NIH researcher, NIH funded trial
• I am not prepared to release the data at this
  point

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Anecdote 2

• Conducting a meta-analysis
• Needed proportions from a published trial that
  reported means and SDs
• I would love to provide you with these data but
  my biostatistician wont allow it

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Anecdote 3

• Wanted data from a large cancer trial to
  illustrate a novel statistical technique
• Investigators were suspicious

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I implore you, oh great king, pity me, poor,
little worm that I am

• We promised
• The data would only be used for a statistical
  methodology study
• We would expressly state in the paper that no
  clinical conclusions should be drawn
• We would slightly corrupt the data
• We would send a draft to the investigators and
  they would have veto power

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Too bad
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How I have done it .

• Show biomed paper
• Link to excel file
• Etc.

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Notice that .

• File is not large (21 Kb)
• File needs no editing

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Why share data?

• Analyses can be reproduced and checked by others
• Acts as an additional incentive for checking that
  a data set is clean and accurate
• May help prevent fraud and selective reporting
• Allows testing of secondary hypotheses
• Aids design of future trials
• Simplifies data acquisition for meta-analysis
• Teaching
• Aids development and evaluation of novel
  statistical methods

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Why share data?

• Analyses can be reproduced and checked by others
• Acts as an additional incentive for checking that
  a data set is clean and accurate
• May help prevent fraud and selective reporting
• Allows testing of secondary hypotheses
• Aids design of future trials
• Simplifies data acquisition for meta-analysis
• Teaching
• Aids development and evaluation of novel
  statistical methods

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Reported results

• Sensitivity of 100
• Specificity of 95

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Conclusions

• We compared SELDI proteomic spectra from three
  experiments on ovarian cancer.
• These spectra are available on the web at
  http//clinicalproteomics.steem.com
• The results were not reproducible across
  experiments.

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Key point

• Publication of raw data is routine for
• Protein chemistry
• Genomic research
• Astronomy
• But not clinical trials

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Why share data?

• Analyses can be reproduced and checked by others
• Acts as an additional incentive for checking that
  a data set is clean and accurate
• May help prevent fraud and selective reporting
• Allows testing of secondary hypotheses
• Aids design of future trials
• Simplifies data acquisition for meta-analysis
• Teaching
• Aids development and evaluation of novel
  statistical methods

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Acts as an additional incentive for checking that
a data set is clean and accurate

• My house is neater when I know someone is coming
  to visit
• Biomarker study
• Gross errors found in clinical trial data set

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May help prevent fraud and selective reporting
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Allows testing of secondary hypotheses

• CARET study do vitamins help prevent lung
  cancer?
• Peter Bach at MSKCC what is the association
  between amount of cigarette smoking and lung
  cancer?
• Predictive model
• Used to evaluate CT screening for lung cancer

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Aids design of future trials

• Numerous decisions on trial design should be
  based on data
• How many patients do we need?
• When should we measure patients?
• What is the best way to measure outcome?

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Simplifies data acquisition for meta-analysis

• A single study rarely tells you much
• Combine data from several studies to get the big
  picture meta-analysis
• Can be difficult to combine data if results are
  presented in different ways

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Teaching

• Best way to teach swimming is to put your
  children in the water
• Best way to teach statistics is to have students
  analyze real data sets

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Development of novel statistical methods
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Arguments against data sharing

• Cost and trouble of putting data set together
• Doesnt this have to be done anyway?

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Arguments against data sharing 2

• It might violate patient privacy
• Changing names to codes and dates to lengths of
  time is hardly rocket science

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Arguments against data sharing 3

• Other researchers might conduct invalid analyses
• A decision for the scientific community as a whole

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Arguments against data sharing 4

• Researchers have a right to exploit data that
  they may have spent years collecting

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A code of conduct for sharing data from clinical
trials

• Independent investigators planning to publish a
  new analysis should contact the trialists before
  undertaking any analyses
• One or more trialists should be offered a
  co-authorship or opportunity to write a
  commentary published alongside the new analysis
• Journals should not publish new analyses of
  previously published data unless a trialist is
  co-author or writes separate commentary
• Published new analyses should cite the original
  trial

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Code of conduct for trialists

• Data set must be clean, well annotated,
  de-identified
• Publish immediately data for the main analyses
• No need to share data for planned 2ry analyses
• All raw data made available no longer than five
  years after first publication of trial results
• There is no need to update data
• Trialists must share data if analyses are not to
  be published

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• To the Editor
• Cancer Data? Sorry, Cant Have It (Essay, Jan.
  22) Andrew Vickers hints at a truth known to
  most physicians with any connection to medical
  research the pursuit of academic and scientific
  prestige is often as important as the potential
  benefit to patients. Theres a simple fix. If the
  top dozen or so medical journals refused to
  consider publication of any research results
  without a pledge from the authors to make the raw
  data available for follow-up analysis, the
  problem would disappear.
• David R. Bacon, M.D.

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Will journals step up to the plate?

• Should the results of human experimentation
  become personal property of the researchers?
• Publication
• Ethical approval
• Disclosure of conflict of interest
• Data made publicly available