current pediatric research limits and promises
DESCRIPTION
Description of current pediatric research agenda. Introduction to translational research.TRANSCRIPT
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Pediatric Research
Current state, difficulties and promises
F. Cachat1,2
1Pediatric Department, Samaritain Regional Hospital, Vevey, 2Départment of pediatrics, Pediatric Nephrology Unit, University Hospital, Lausanne, Switzerland
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Aims
• How research is conducted around the world
• Current limitations to research
• Solutions to improve research
The challenges of research
The rewards of research
Finding cures / improving health delivery to the patient
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Research question
ClinicalAnswer
Researchstaff
ResearchStaff recruitment / retention / mentoring
Clinical questionformulation
Targeted population
Population study generalization / minorities
Study type
Limitationsof studies / RCT
Generalizationof findings
ImplementationsGuidelines formulation
Clinical researchmethodology
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Where do we come from / current state
• Numbers of pediatric trials
Medline:
- Child and Hypertension
- Child and RCT
Research in Pediatrics
0
5000
10000
15000
20000
25000
1960-1970 1971-1980 1981-1990 1991-2000 2001-2010
Decades
Nu
mb
er o
f p
ub
licat
ion
s
Steadily increase in thenumber of clinical studies
involving children over the lasttwo decades, especially RCTespecially RCT
Steadily increase in thenumber of clinical studies
involving children over the lasttwo decades, especially RCTespecially RCT
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Where and how is pediatric research performed / current state
0
500
1000
1500
2000
2500
3000
3500
4000
4500
1960-1970
1971-1980
1981-1990
1991-2000
2001-2010
USA
England
Switzerland
India
Increase in RCT in the USAbut also in developing in developing
countriescountries (India, China…)
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Where and how is pediatric research performed / current state
RCT in majorRCT in major vs. smallresearch centers
0
50
100
150
200
250
300
350
400
450
1960-1970
1971-1980
1981-1990
1991-2000
2001-2010
Boston
Lexington
Lausanne
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Introduction summary 1
• Dramatic increase in the number of RCT performed children over the last 50 years, mainly over the last 10-20 years all over the world
• Research concentrates in the USA and Europe
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Introduction summary 2
• Increasing importance of clinical research originating and/or taking place in developing countries
• Research still concentrates in major academic centers
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Clinical question
Answer
Researchstaff
ResearchStaff recruitment / retention / mentoring
Clinical questionformulation
Targetedpopulation
Population study generalization / minorities
Study type
Limitationsof studies / RCT
Generalizationof findings
ImplementationsGuidelines formulation
Clinical researchmethodology
Determinant of research
Determinant of research
PotentialdifficultiesPotential
difficulties
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Current limitations: research faculty
• Research faculty recruitment and retention
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Current limitations: research faculty
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• Mentoring• Career planning• Performance feedback• Professional network• Connectedness and acculturation to medical school
• To improve faculty satisfaction, productivity, To improve faculty satisfaction, productivity, institutional loyalty and retentioninstitutional loyalty and retention
Solution: Faculty Development Program
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Solution: training in research / better mentoring
Mentee or Protégé
Mentor
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Clinical question
Answer
Researchstaff
ResearchStaff recruitment / retention / mentoring
Clinical questionformulation
Targetedpopulation
Population study generalization / minorities
Study type
Limitationsof studies / RCT
Generalizationof findings
ImplementationsGuidelines formulation
Clinical researchmethodology
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Research settings / targeted population
Population with condition X
Studypopulation
Conclusions
1
2
1. Is the study population representative of the general population?Internal and external validity of the study
2. Are the conclusions of the study applicable to the general population?Implementation of the findings to the general population / translational research
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Research settings / targeted population
• Biais of recruitment
Sexe Age Race
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Research settings / targeted population
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Is the population representative of my patients?
Is the research standart adequate?
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Clinical question
Answer
Researchstaff
ResearchStaff recruitment / retention / mentoring
Clinical questionformulation
Targetedpopulation
Population study generalization / minorities
Study types
Limitations ofstudies / RCT
Clinical researchmethodology
Generalizationof findings
ImplementationsGuidelines formulation
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Current limitations of RCT
• (Extremely) long-term outcomes for most of the chronic diseases (heart failure, chronic kidney diseases, dementia, psychosis, asthma…)
• (Major) discrepancies in major studies findings and (prohibitive) cost of major clinical studies
• (Extremely) limited benefit of new drugs
• (Poor) generalizability / implementation of RCT findings
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RCT long-term results
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RCT long-term results
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Current limitation: long-term studies
Treatment
Placebo
Treatment vs.placebo Surveillance
Years (/decades)
Outcome
Years (/decades)
RCT long-term results
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RCT
Cohortstudies
Solution: cohort studiescohort studiessystematic reviews / meta-analysis
RCT long-term results
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RCT long-term results
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RCT long-term results
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RCT conflicting results
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RCT conflicting results
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Solution: cohort studiessystematic reviews / meta-analysissystematic reviews / meta-analysis
RCT conflicting results / meta-analysis
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New treatment against what?
Rejection of H0One tailed test
10%Response rate
30%Response rate
Small number of subjects
RCT against placebo
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RCT best available treatment
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New treatment against what?
Rejection of H0One tailed test
Non inferiority trialsEquivalence trials
30%Response rate
35%Response rate
Sample size considerable larger thanplacebo-controlled trials
RCT bestavailable treatment
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Equivalence, non-inferiority and superiority trials
Superiority trial
Non inferiority trial
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Equivalence, non-inferiority and superiority trials
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Clinical question
Answer
Researchstaff
ResearchStaff recruitment / retention / mentoring
Clinical questionformulation
Targetedpopulation
Population study generalization / minorities
Study types
Limitations ofstudies / RCT
Clinical researchmethodology
Generalizationof findings
ImplementationsGuidelines formulation
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Basic research
Biomarkers(PSA, CRP…)
TranslationalTranslationalResearch Type IResearch Type I
Individual patient
CommunityTranslationalTranslational
Research Type IIResearch Type II
Clinicaltrials
Evidence(Guidelines…)
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Translational research
• The integration of advancements in molecular biology or other basic science to the individual (type I), and from the advancement of clinical trials to the community (type II)
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Translational research type II
• Implementation of RCT findings into the community
• There is a massive lack of type II translational research
• State of the affair:
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Barriers to implementation
• Unaware of the guidelines• Mistrust of guidelines• Guidelines too complicated• Lack of time, resources• Peer pressure• Patient’s preference
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Conclusions (1)
• Clinical research in pediatrics has made substantial progress over the last decades
• Better regulation
• Better participant protection
• Better research methodologies / collaboration
• Major challanges for the next years• Long-term studies
• Minorities inclusions
• Funding issues
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Conclusions (2)
• Agenda • Better and earlier training for medical students, residents
and fellow• Better career plan for clinician-scientists• Better collaboration between researchers and clinicians,
between pediatric and adult specialists• Develop and implement translational research type I and II
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Outline
• Where do we stand now?– Progression over the last decade
– Where is pediatric research currently performed?
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Outline
• Where are the limitations?– People:
• Faculty recruitment / motivation / training
– Location: • University-based research vs. office-based and potential biais
• Developing countries research and potential risks
– Research subject protection:• Research involving minorities (pregnancy, newborn, ethnic minorities, orphan diseases) and potential
risks
– Research design: • Long-term studies: inherent difficulties (time lag)
• RCT: inherent difficuties (placebo-controlled studies (best treatment vs placebo / non inferiority trials / power)
• Implementation of basic or clinical findings (translational research)
• Funding issues
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Outline• How to improve
– People: • Early student / resident / fellow involvment
• Mentoring
– Location: • Office-based research / community research / network studies
• Top-bottom and bottom-up research
• Regulations / subject protection
– Research subject protection:• Enrollement of minorities
• Regulations
• Clinical research centers
– Research design: • Cohort studies / systematic reviews – meta-analysis
• Translational research type I and II