G. Biondi Zoccai – Ricerca in cardiologia RICERCA CLINICA IN CARDIOLOGIA INTERVENTISTICA (2/2)...

G. Biondi Zoccai – Ricerca in cardiologiaRICERCA CLINICA IN CARDIOLOGIA

INTERVENTISTICA (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

G. Biondi Zoccai – Ricerca in cardiologia

What to expect?

Core modules

• IntroductionIntroduction

• Finding out relevant literatureFinding out relevant literature

• General guidelines for literature appraisalGeneral guidelines for literature appraisal

• Abstract and Introduction appraisalAbstract and Introduction appraisal

• Methods and Results appraisal 1Methods and Results appraisal 1 - - Patients and proceduresPatients and procedures

• Methods and Results appraisal 2Methods and Results appraisal 2 - - Data collection/management and Data collection/management and

descriptive analysisdescriptive analysis

• Methods and Results appraisal 3Methods and Results appraisal 3 - - Inferential analysisInferential analysis

• Discussion and Conclusions appraisalDiscussion and Conclusions appraisal


Topics of this presentationTopics of this presentation

• Study designStudy design

• Patient characterizationPatient characterization

• ProceduresProcedures

• Follow-upFollow-up

• End-pointsEnd-points

• Additional analysesAdditional analyses


Study designStudy design

The study design should be clearly stated either The study design should be clearly stated either

in the end of the Introduction, or in the Methods in the end of the Introduction, or in the Methods

BEWARE IF IT IS NOT CLEARLY STATED!BEWARE IF IT IS NOT CLEARLY STATED!

• Focus on prospective vs retrospective designFocus on prospective vs retrospective design

• Clarify whether the study was single or multicenterClarify whether the study was single or multicenter

• Is the study beneficial to any third party (eg sponsor)? If yes, assess Is the study beneficial to any third party (eg sponsor)? If yes, assess

whether it was spontaneous or funded, and whether any conflict of whether it was spontaneous or funded, and whether any conflict of

interest is presentinterest is present

Remember, not telling the whole truth is much more common Remember, not telling the whole truth is much more common

than telling lies, but nonetheless may be done than telling lies, but nonetheless may be done

on purpose to fool the readers! on purpose to fool the readers!


Study designStudy design

Ardissino JAMA 2004




• Patient selection/characterizationPatient selection/characterization






PatientsPatients

Clear statements on the selection of patients are pivotalClear statements on the selection of patients are pivotal

to explicitly identify the target populationto explicitly identify the target population

BEWARE IF THEY ARE NOT CLEARLY STATED!BEWARE IF THEY ARE NOT CLEARLY STATED!

• Focus on inclusion vs exclusion criteriaFocus on inclusion vs exclusion criteria

• Focus on consecutive vs purposeful enrolmentFocus on consecutive vs purposeful enrolment

• Is the patient population highly selected or are they everyday subjects?Is the patient population highly selected or are they everyday subjects?• Do authors provide separate numbers of patients screened, enrolled Do authors provide separate numbers of patients screened, enrolled

and randomizedand randomized

Remember, a highly selected population will provide more internally Remember, a highly selected population will provide more internally

valid answers, but at the price of lower external validityvalid answers, but at the price of lower external validity


PatientsPatients

Ardissino JAMA 2004


PatientsPatients


PatientsPatients

Biondi Zoccai Ital Heart J 2003


ProceduresProcedures

Clear statements on the interventional procedures are Clear statements on the interventional procedures are

pivotal to ensure reproducibility of outcomespivotal to ensure reproducibility of outcomes

BEWARE IF THEY ARE NOT CLEARLY STATED!BEWARE IF THEY ARE NOT CLEARLY STATED!

• Focus on technical aspects, devices, and safety measuresFocus on technical aspects, devices, and safety measures

• Additional therapies are important as well (eg thienopyridines)Additional therapies are important as well (eg thienopyridines)

• Can the techniques described be reasonably performed in other cath Can the techniques described be reasonably performed in other cath

labs with the available equipments and expertise?labs with the available equipments and expertise?

• Do authors provide accurate data on the management of all scenarios Do authors provide accurate data on the management of all scenarios

(even the worst case one)?(even the worst case one)?

Remember, centers with a specific expertise in a technique or device Remember, centers with a specific expertise in a technique or device

might provide results that are not easily reproducible by othersmight provide results that are not easily reproducible by others



Ardissino JAMA 2004



Colombo CCI 2005


Follow-upFollow-up

Follow-up procedures should be standardized and Follow-up procedures should be standardized and

equally applied to all relevant patient groupsequally applied to all relevant patient groups

• Focus on follow-up techniques (eg lab tests, ECG, phone interview, Focus on follow-up techniques (eg lab tests, ECG, phone interview,

office visit,…)office visit,…)

• Clearly identify follow-up duration (mean, median, standard deviation, Clearly identify follow-up duration (mean, median, standard deviation,

range,…). Is it similar in the groups being compared?range,…). Is it similar in the groups being compared?

• Was enrolment going over for a long time or limited to a brief time Was enrolment going over for a long time or limited to a brief time

frame?frame?

• Were there drop-outs, drop-ins, non-compliant pts, or losses to follow-Were there drop-outs, drop-ins, non-compliant pts, or losses to follow-

up? up?

Remember, for clinical studies a Remember, for clinical studies a >>95% follow-up 95% follow-up

is mandatory to limit the risk of attrition bias is mandatory to limit the risk of attrition bias


Follow-upFollow-up

Holmes JAMA 2006


Follow-upFollow-up

Ardissino JAMA 2004


End-pointsEnd-points

Clear statements on the primary, secondary, and Clear statements on the primary, secondary, and

additional end-points are paramount. additional end-points are paramount.

In case of doubt, remain skeptical! In case of doubt, remain skeptical!

BEWARE OF SECONDARY END-POINTS BEWARE OF SECONDARY END-POINTS

OR SUB-GROUP ANALYSES! OR SUB-GROUP ANALYSES!

• Focus on the primary end-point, as this was the only one for which the Focus on the primary end-point, as this was the only one for which the

study was truly poweredstudy was truly powered• Check for spurious inconsistencies between primary vs secondary or Check for spurious inconsistencies between primary vs secondary or

efficacy vs safety end-pointsefficacy vs safety end-points• Were outcome assessors unaware of treatment assignment?Were outcome assessors unaware of treatment assignment?• Sub-group analyses are by definition (unless otherwise stated) Sub-group analyses are by definition (unless otherwise stated)

hypothesis-generating. In any case, the risks of alpha error and hypothesis-generating. In any case, the risks of alpha error and

biological non-plausibility applybiological non-plausibility apply



Ardissino JAMA 2004



Holmes JAMA 2006


Additional analysesAdditional analyses

Additional analyses (eg, QCA, IVUS, TIMI flow, Additional analyses (eg, QCA, IVUS, TIMI flow,

troponin release) are important in that they troponin release) are important in that they

may drive the primary end-point (eg, TLR) may drive the primary end-point (eg, TLR)

or substantiate it indirectly (eg TIMI flow) or substantiate it indirectly (eg TIMI flow)

• Focus on technical aspects, devices, software and reproducibilityFocus on technical aspects, devices, software and reproducibility

• Was personnel involved in additional analyses unaware of treatment Was personnel involved in additional analyses unaware of treatment

assignment?assignment?

• Beware of tautology issuesBeware of tautology issues

• Some studies may indeed have more a pathophysiological than a Some studies may indeed have more a pathophysiological than a

clinical edgeclinical edge

Remember that additional analyses shouldRemember that additional analyses should

be distinguished from cosmetic analysesbe distinguished from cosmetic analyses



Windecker NEJM 2005

G. Biondi Zoccai – Ricerca in cardiologia RICERCA CLINICA IN CARDIOLOGIA INTERVENTISTICA (2/2)...

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