Alastair Hay, Consultant Senior Lecturer in Primary Health Care

The TARGET Programme: strengths, weaknesses, opportunities and lessons

learned (so far).

What is the problem?• High rates of RTIs in children lead to

• Economic burden to health services and parents (and their employers)

• Unnecessary use of antibiotics leads toIncreased selective pressure on antimicrobial

resistance andMedicalisation of illness vicious or virtuous circle

• Clinical uncertainty drives use but leads to low specificity

2

What does the TARGET team believe is the solution?

• Clinical prediction rule?• Yes, but…

What to “predict” (diagnosis vs. prognosis)? Which symptoms and signs to measure? How would a prediction rule fit into current clinical

practice (simple vs. complex intervention)?

3

Programme overview4

Parent Clinician Child

WS2* - Qualitative studies

Parent knowledge, health seeking behaviour

and information needs

WS1* - Systematic reviews

a) Factors associated with frequent attendance b) Natural history of RTI symptoms in childhood;

WS3* - Prospective cohort study

Clinical (and microbiological) factors associated with poor

prognosis to derive and validate a clinical rule to

predict hospitalisation from RTI

WS4* - cluster randomised controlled

trial Clinical and cost effectiveness of clinical

rule + parent information

Years 1

2

3

4

5

Programme overview5

Parent Clinician Child

WS2* - Qualitative studies

Parent knowledge, health seeking behaviour

and information needs

WS1* - Systematic reviews

a) Factors associated with frequent attendance b) Natural history of RTI symptoms in childhood;

WS3* - Prospective cohort study

Clinical (and microbiological) factors associated with poor

prognosis to derive and validate a clinical rule to

predict hospitalisation from RTI

WS4* - cluster randomised controlled

trial Clinical and cost effectiveness of clinical

rule + parent information

Years 1

2

3

4

5

WS3 – CPR study

• Research questions • Can baseline characteristics be used to

predict the need for hospitalisation in children <12 years presenting to primary care with acute cough?

• Do specific bacteria and/or viral microbes (or combinations of microbes) predict poor prognosis?

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WS3 – CPR study

• Design: prospective cohort (derivation and validation) study

• Eligibility: Children <12 years presenting to primary care with acute cough

• Independent variables• Baseline symptoms and signs + other

characteristics (e.g. deprivation)• Detailed microbiology and virology

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WS3 – CPR study

• Dependent variables• Primary – hospitalisation• Secondary - symptom duration, symptom

severity, antibiotic prescribing and reconsultations

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WS3 – CPR study

• Challenges• How to determine sample size• Logistics of recruiting a large cohort• Minimising (and/or adjusting for) spectrum

bias• Confounding by indication

9

WS3 – CPR study

• Sample size methods1. Certainty with which strength of association

between individual predictors and outcome

2. Overall precision of the sensitivity and specificity of a validated rule

3. Ratio of candidate predictors to outcome events

10

WS3 – CPR study

• Recruitment logistics• Collaboration• Simple data collection proforma• Web and paper based• Re-imbursement for clinician time

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DESCARTE pooled recruitment up to end of May 2009(Consent Form Data)

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Months of study

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Actual cumulative recruitment

WS3 – CPR study

• Spectrum bias• Difference in illness (e.g. aetiology) between

derivation and validation datasets• Can undermine validation• One potential solution is to anticipate which

parameters are most likely to change and• Measure them (e.g. microbiology)• Adjust analysis for them

13

WS3 – CPR study

• Confounding by indication• Can potentially be reduced by

Derive and validate in the control arm of a RCT (unlikely to be ethical)

Assume that antibiotic prescribing is not associated with risk of outcome and exclude children prescribed antibiotics

Include all children, look for association between antibiotics and key predictors and model antibiotic effects

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Summary

• Albeit with some limitations, CPRs can be appropriately applied in the infection field. Limitations include• Spectrum bias• Confounding by indication (antibiotic use)

• Logistic challenges of recruiting large sample sizes• Collaboration• Use of technology to help manage data

• Funders want to support CPR research