The principal investigator must ensure the safety and integrity of
individual
patients participating in the trial. He or she is responsible for
assessing,
recording and reporting information of all adverse events related to
the
treatment or procedure, and all serious or unexpected adverse events
that
may occur during the conduct of the trial.
The establishment of a special committee to monitor adverse events
should
be considered, especially in large trials. Safety-monitoring
committees
(often known as Data Monitoring Committees) should include clinicians
with
expertise in the topic under trial, bio-statisticians, and researchers
from
other relevant fields (see Trial Management).
Members of the safety-monitoring committee are responsible for giving
advice
to the principal investigator on whether to a) continue as planned b)
stop further recruitment or c) discontinue the intervention if there
is
evidence that the latter is substantially better (or worse) than the
alternatives.
Sometimes it is recommended that the intervention be modified (e.g.
treatment
dosage reduced or one treatment arm stopped in a multiple arm
trial).
Such data and safety monitoring committees often use statistical
stopping
rules to help with their decision making.
It is important that members of the data monitoring committee are
independent
of the trial. Knowledge of the data or emerging trends may make
the
investigator in charge of patient recruitment reluctant to enrol new
patients
or to continue treating those already enrolled if the data suggests one
intervention
is better than the other.
Illustrative example - WHO pre-eclampsia
trial
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Analysis plan |
Illustrative example - CRASH trial
|
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Organisation The independent Data Monitoring Committee will conduct interim analyses of mortality and morbidity among all trial participants. It will advise the Steering Group if the randomised comparisons in the trial provide both (i) proof beyond reasonable doubt of a difference in outcome between the study and control groups, and (ii) evidence that would be expected to alter substantially the choice of treatment for patients whose doctors are, in the light of the evidence from other randomised trials, substantially uncertain whether to give corticosteroids to patients with head injury. (CRASH Trial - go to protocol) go to protocol ) |
Illustrative example - Perinatal care trial
|
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Interim Analysis and Study Monitoring NICHD will determine the members of the DSMB that will be responsible for monitoring the project. (CLAP Trial - go to protocol) go to protocol ) |
This checklist has been contributed by Dave Sackett, who prepared it
for the forthcoming 3rd edition of Clinical Epidemiology; A Basic
Science for Answering Questions about Health Care, to be published by
Lippincott, Williams & Wilkins in 2005.
This text has been contributed by Dave Sackett, who prepared it
for
the forthcoming 3rd edition of Clinical Epidemiology; A Basic Science
for
Answering Questions about Health Care, to be published by Lippincott,
Williams
& Wilkins in 2005.