RICERCA CLINICA
IN CARDIOLOGIA
INTERVENTISTICA
G. Biondi Zoccai – Ricerca in cardiologia
(2/2)
Percorso didattico basato sulla
revisione ed interpretazione dei dati
derivanti dalla letteratura scientifica
Giuseppe Biondi Zoccai, Divisione di Cardiologia 1,
Ospedale S. Giovanni Battista “Molinette”, Torino
[email protected] – http://www.metcardio.org
What to expect?
G. Biondi Zoccai – Ricerca in cardiologia
Core modules
•
Introduction
•
Finding out relevant literature
•
General guidelines for literature appraisal
•
Abstract and Introduction appraisal
•
Methods and Results appraisal 1 - Patients and procedures
•
Methods and Results appraisal 2 - Data collection/management and
descriptive analysis
•
Methods and Results appraisal 3 - Inferential analysis
•
Discussion and Conclusions appraisal
Topics of this presentation
G. Biondi Zoccai – Ricerca in cardiologia
• Study design
• Patient characterization
• Procedures
• Follow-up
• End-points
• Additional analyses
Topics of this presentation
G. Biondi Zoccai – Ricerca in cardiologia
• Study design
• Patient characterization
• Procedures
• Follow-up
• End-points
• Additional analyses
Study design
G. Biondi Zoccai – Ricerca in cardiologia
The study design should be clearly stated either
in the end of the Introduction, or in the Methods
BEWARE IF IT IS NOT CLEARLY STATED!
•
Focus on prospective vs retrospective design
•
Clarify whether the study was single or multicenter
•
Is the study beneficial to any third party (eg sponsor)? If yes, assess
whether it was spontaneous or funded, and whether any conflict of
interest is present
Remember, not telling the whole truth is much more common
than telling lies, but nonetheless may be done
on purpose to fool the readers!
Study design
G. Biondi Zoccai – Ricerca in cardiologia
Ardissino JAMA 2004
Topics of this presentation
G. Biondi Zoccai – Ricerca in cardiologia
• Study design
• Patient selection/characterization
• Procedures
• Follow-up
• End-points
• Additional analyses
Patients
G. Biondi Zoccai – Ricerca in cardiologia
Clear statements on the selection of patients are pivotal
to explicitly identify the target population
BEWARE IF THEY ARE NOT CLEARLY STATED!
•
Focus on inclusion vs exclusion criteria
•
Focus on consecutive vs purposeful enrolment
•
•
Is the patient population highly selected or are they everyday subjects?
Do authors provide separate numbers of patients screened, enrolled
and randomized
Remember, a highly selected population will provide more internally
valid answers, but at the price of lower external validity
Patients
G. Biondi Zoccai – Ricerca in cardiologia
Ardissino JAMA 2004
Patients
G. Biondi Zoccai – Ricerca in cardiologia
Patients
G. Biondi Zoccai – Ricerca in cardiologia
Biondi Zoccai Ital Heart J 2003
Topics of this presentation
G. Biondi Zoccai – Ricerca in cardiologia
• Study design
• Patient selection/characterization
• Procedures
• Follow-up
• End-points
• Additional analyses
Procedures
G. Biondi Zoccai – Ricerca in cardiologia
Clear statements on the interventional procedures are
pivotal to ensure reproducibility of outcomes
BEWARE IF THEY ARE NOT CLEARLY STATED!
•
Focus on technical aspects, devices, and safety measures
•
Additional therapies are important as well (eg thienopyridines)
•
Can the techniques described be reasonably performed in other cath
labs with the available equipments and expertise?
•
Do authors provide accurate data on the management of all scenarios
(even the worst case one)?
Remember, centers with a specific expertise in a technique or device
might provide results that are not easily reproducible by others
Procedures
G. Biondi Zoccai – Ricerca in cardiologia
Ardissino JAMA 2004
Procedures
G. Biondi Zoccai – Ricerca in cardiologia
Procedures
G. Biondi Zoccai – Ricerca in cardiologia
Colombo CCI 2005
Topics of this presentation
G. Biondi Zoccai – Ricerca in cardiologia
• Study design
• Patient selection/characterization
• Procedures
• Follow-up
• End-points
• Additional analyses
Follow-up
G. Biondi Zoccai – Ricerca in cardiologia
Follow-up procedures should be standardized and
equally applied to all relevant patient groups
•
Focus on follow-up techniques (eg lab tests, ECG, phone interview,
office visit,…)
•
Clearly identify follow-up duration (mean, median, standard deviation,
range,…). Is it similar in the groups being compared?
•
Was enrolment going over for a long time or limited to a brief time
frame?
•
Were there drop-outs, drop-ins, non-compliant pts, or losses to followup?
Remember, for clinical studies a >95% follow-up
is mandatory to limit the risk of attrition bias
Follow-up
G. Biondi Zoccai – Ricerca in cardiologia
Holmes JAMA 2006
Follow-up
G. Biondi Zoccai – Ricerca in cardiologia
Holmes JAMA 2006
Follow-up
G. Biondi Zoccai – Ricerca in cardiologia
Ardissino JAMA 2004
Topics of this presentation
G. Biondi Zoccai – Ricerca in cardiologia
• Study design
• Patient selection/characterization
• Procedures
• Follow-up
• End-points
• Additional analyses
End-points
G. Biondi Zoccai – Ricerca in cardiologia
Clear statements on the primary, secondary, and
additional end-points are paramount.
In case of doubt, remain skeptical!
BEWARE OF SECONDARY END-POINTS
OR SUB-GROUP ANALYSES!
•
•
•
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Focus on the primary end-point, as this was the only one for which the
study was truly powered
Check for spurious inconsistencies between primary vs secondary or
efficacy vs safety end-points
Were outcome assessors unaware of treatment assignment?
Sub-group analyses are by definition (unless otherwise stated)
hypothesis-generating. In any case, the risks of alpha error and
biological non-plausibility apply
End-points
G. Biondi Zoccai – Ricerca in cardiologia
Ardissino JAMA 2004
End-points
G. Biondi Zoccai – Ricerca in cardiologia
Holmes JAMA 2006
End-points
G. Biondi Zoccai – Ricerca in cardiologia
Topics of this presentation
G. Biondi Zoccai – Ricerca in cardiologia
• Study design
• Patient selection/characterization
• Procedures
• Follow-up
• End-points
• Additional analyses
Additional analyses
G. Biondi Zoccai – Ricerca in cardiologia
Additional analyses (eg, QCA, IVUS, TIMI flow,
troponin release) are important in that they
may drive the primary end-point (eg, TLR)
or substantiate it indirectly (eg TIMI flow)
•
Focus on technical aspects, devices, software and reproducibility
•
Was personnel involved in additional analyses unaware of treatment
assignment?
•
Beware of tautology issues
•
Some studies may indeed have more a pathophysiological than a
clinical edge
Remember that additional analyses should
be distinguished from cosmetic analyses
Additional analyses
G. Biondi Zoccai – Ricerca in cardiologia
Additional analyses
G. Biondi Zoccai – Ricerca in cardiologia
Windecker NEJM 2005