Current pediatric research limits and promises

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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

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

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

5

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…)

6

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

Clinical question

Answer

Researchstaff



Targetedpopulation


Study type





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

• 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

Solution: training in research / better mentoring

Mentee or Protégé

Mentor

Clinical question

Answer

Researchstaff



Targetedpopulation


Study type





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


• Biais of recruitment

Sexe Age Race

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Is the population representative of my patients?

Is the research standart adequate?

Clinical question

Answer

Researchstaff



Targetedpopulation


Study types

Limitations ofstudies / RCT




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

RCT long-term results

Current limitation: long-term studies

Treatment

Placebo

Treatment vs.placebo Surveillance

Years (/decades)

Outcome

Years (/decades)


RCT

Cohortstudies

Solution: cohort studiescohort studiessystematic reviews / meta-analysis


RCT conflicting results

Solution: cohort studiessystematic reviews / meta-analysissystematic reviews / meta-analysis

RCT conflicting results / meta-analysis

New treatment against what?

Rejection of H0One tailed test

10%Response rate

30%Response rate

Small number of subjects

RCT against placebo

RCT best available treatment

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

Equivalence, non-inferiority and superiority trials

Superiority trial

Non inferiority trial

Equivalence, non-inferiority and superiority trials

Clinical question

Answer

Researchstaff



Targetedpopulation


Study types

Limitations ofstudies / RCT




Basic research

Biomarkers(PSA, CRP…)

TranslationalTranslationalResearch Type IResearch Type I

Individual patient

CommunityTranslationalTranslational

Research Type IIResearch Type II

Clinicaltrials

Evidence(Guidelines…)

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?

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

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

Current pediatric research limits and promises

Health & Medicine

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