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Clinical
Trial Performance
Peter Doran
UCD School of Medicine & Medical Science

Scoil an Leighis agus Eolaíocht an Leighis UCD
Characteris2cs
•  What is difference between a “good” clinical

trial and a “bad” one?
•  Good= well designed and executed

Scenario
•  You have been asked to review a clinical trial

protocol and to comment on it
•  What criteria would you use to

–  1) judge quality of trial design
–  2) gauge the performance of the study

Measures of quality?

Published?

Ins2tu2on?

Journal?

Scoil an Leighis agus Eolaíocht an Leighis UCD Impact Factor 9.8
•  Trial Is published
•  Good insVtuVon
•  Good Journal
=Good Trial

Other Criteria?

Accuracy of Results (i)
•  Do results reflect the true data

•  Do they support / refute the hypothesis
•  Are results valid?

Are Results useful? (ii)
•  PosiVve results usually more useful than negaVve
•  Is trial designed to give posiVive results
•  How might this be effected by study design?
–  Is quesVon well formed

–  How can data be used by paVents / physicians

Is Trial Safe? (ii)
•  Does trial protect safety?

•  Is it ethical
•  Does it limit risk by having smallest n possible?

Feasibility (iv)
•  Cost of trial

•  Equipment / experVse needed

Overall Criteria
•  Accurate
•  Useful
•  Safe
•  Feasible

» More detailed consideraVon of these

Accuracy
•  Clinical trial must yield the correct answer to the

quesVon that is asked
•  What might impact on accuracy
•  Categories
–  Accurate
–  Inaccurate
–  Uninterpretable

Accurate Result
•  Accurate Result;
–  Well designed trial maximises chance of accurate
result
–  posiVveresult (staVsVcally significant) when the
drug works,
–  negaVve result (lack of significance) when the
drug does not.

Inaccurate Result
•  StaVsVcal Fluke
•  Error
•  PosiVve result when the drug does not actually
work,
•  NegaVve result when it does work.
•  How do we know?

–  Repeat trials
–  Metanalysis

Uninterpretable result
•  Worst result of a clinical trial

•  Cant interpret the data either way
–  Insufficient data
–  Wrong data
–  Wrong N
–  Wrong dose / schedule
–  Bias not minimised

Bias
•  Error that will make one arm of the study

superior, when in fact there is no difference
•  We need to control all variables except the

one being compared

Bias
Control IntervenVon
Whats difference between the groups?

Where does bias come from?

Sources of bias
•  Design
•  Controlled sedng of clinical trials – care is not
standard
•  Drop outs/ loss to follow up
•  Regression to the mean
•  Inter observer variability
•  Training
–  Good trial design will reduce these

•  Has internal validity

Types of Bias
•  SystemaVc bias
–  Affects all of the study
–  Affect control and treatment arms
–  Can sVll draw conclusions
•  DifferenVal bias
–  Affect one arm of study
–  Impacts internal validity
–  Start of Study
•  E.g paVent characterisVcs at baseline
–  During Study
•  Differences in assesments, dropout rates etc
•  Safety withdrawls

Study design
•  Is study designed to give maximum chance of

posiVve result?
•  Goal of clinical trial is to show therapy is
–  Safe
–  EffecVve
•  The study must ask the right quesVon?
–  Non inferiority study

Study Design
•  To maximise clinical trial performance need to

select
–  Right design
–  Right populaVon
–  Right drug
–  Right endpoint
•  Get any of these wrong and study will be compromised

Usefulness
•  Are results generisable?

•  Results of clinical trial must be useful in clinical
pracVce
•  Study must have external validity
•  The characterisVcs of the
–  paVents,
–  intervenVon, and
–  outcome,
•  must be close enough to clinical pracVce in order
to be transferable to everyday pracVce.

Usefulness
•  Are results acVonable

–  Has drug been administered in such a way as can
be replicated in normal clinical pracVce
•  Drug stability
•  FormulaVon
•  Dosing

Phase Dependency
•  EvaluaVon criteria are different for different

phase trials
•  E.g Phase 1 not generisable nor acVonable
•  BUT DO ENABLE NEXT PHASES

Safe and Ethical
•  Do no harm
•  Note
–  Goal of clinical trial is not to benefit the paVent, but
rather to test the hypothesis!
–  All studies expose paVents to risk

•  How do we minimise this risk?
–  Well designed clinical trial will use smallest number of

parVcipants

Feasibility
•  Well designed study will yield high quality

data
•  Data collecVon must be feasible
•  Burden of
–  InvesVgators
–  Trial staff
–  paVents

Key Design Parameters
•  Criteria
–  it must have internal and external validity
–  maximize the likelihood of a posiVve result,
protect paVent safety, and be
–  feasible and pracVcable.

Clinical Trial Must
•  Ask right quesVon

•  In right group of paVents
•  At right dose and
•  Right Vme

QuesVons


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Clinical

UCD School of Medicine & Medical Science

• What is diﬀerence between a “good” clinical

• Good= well designed and executed

UCD School of Medicine & Medical Science

• You have been asked to review a clinical trial

• What criteria would you use to

UCD School of Medicine & Medical Science

UCD School of Medicine & Medical Science

UCD School of Medicine & Medical Science

UCD School of Medicine & Medical Science

UCD School of Medicine & Medical Science

UCD School of Medicine & Medical Science

UCD School of Medicine & Medical Science

• Do results reﬂect the true data

• Are results valid?

UCD School of Medicine & Medical Science

• PosiVve results usually more useful than negaVve

• Is trial designed to give posiVive results

• How might this be eﬀected by study design?

– Is quesVon well formed

UCD School of Medicine & Medical Science

• Does trial protect safety?

UCD School of Medicine & Medical Science

• Cost of trial

UCD School of Medicine & Medical Science

UCD School of Medicine & Medical Science

• Clinical trial must yield the correct answer to the

• What might impact on accuracy

UCD School of Medicine & Medical Science

UCD School of Medicine & Medical Science

• How do we know?

UCD School of Medicine & Medical Science

• Worst result of a clinical trial

UCD School of Medicine & Medical Science

• Error that will make one arm of the study

• We need to control all variables except the

UCD School of Medicine & Medical Science

Whats diﬀerence between the groups?

UCD School of Medicine & Medical Science

– Good trial design will reduce these

UCD School of Medicine & Medical Science

UCD School of Medicine & Medical Science

• Is study designed to give maximum chance of

UCD School of Medicine & Medical Science

• To maximise clinical trial performance need to

UCD School of Medicine & Medical Science

• Are results generisable?

UCD School of Medicine & Medical Science

• Are results acVonable

UCD School of Medicine & Medical Science

• EvaluaVon criteria are diﬀerent for diﬀerent

• E.g Phase 1 not generisable nor acVonable

• BUT DO ENABLE NEXT PHASES

UCD School of Medicine & Medical Science

– All studies expose paVents to risk

– Well designed clinical trial will use smallest number of

UCD School of Medicine & Medical Science

• Well designed study will yield high quality

UCD School of Medicine & Medical Science

UCD School of Medicine & Medical Science

• Ask right quesVon

UCD School of Medicine & Medical Science

•  What is diﬀerence between a “good” clinical

•  Good= well designed and executed

•  You have been asked to review a clinical trial

•  What criteria would you use to

•  Do results reﬂect the true data

•  Are results valid?

•  PosiVve results usually more useful than negaVve

•  Is trial designed to give posiVive results

•  How might this be eﬀected by study design?

–  Is quesVon well formed

•  Does trial protect safety?

•  Cost of trial

•  Clinical trial must yield the correct answer to the

•  What might impact on accuracy

•  How do we know?

•  Worst result of a clinical trial

•  Error that will make one arm of the study

•  We need to control all variables except the

–  Good trial design will reduce these

•  Is study designed to give maximum chance of

•  To maximise clinical trial performance need to

•  Are results generisable?

•  Are results acVonable

•  EvaluaVon criteria are diﬀerent for diﬀerent

•  E.g Phase 1 not generisable nor acVonable

•  BUT DO ENABLE NEXT PHASES

–  All studies expose paVents to risk

–  Well designed clinical trial will use smallest number of

•  Well designed study will yield high quality

•  Ask right quesVon