CLINICAL TRIALS OF ANTIMICROBIAL AGENTS

Table of Contents

Why do Clinical Trials?

Problems in Clinical Trials

Low Prestige

External Validity

Examples of validity problems:

The Investigator

Acceptance of Bias

Consequences of Bias

It was noted that many patients were had received wrong treatment, i.e. they were randomised to C1 but received C2 or vice versa. An intention-to-treat analysis in which all patients were analysed as randomised showed a ?2 of 1.5 and a P-value ?.5.

Lack of Funding

The Ideal Trial Points to Consider

The trial protocol should include an introductory section describing the disease and the drugs studied; adequate references should be added. 

2. Rationale and Trial Hypothesis

Type I (alpha) Error

Type II (beta) Error)

3. Trial Design

3.1 Controls

Other controls are active drug or dose titrations

3.2 Randomisation

3.3 Blinding

4. Patient sample

The method by which patients are to be recruited should be described (from patients normally seeking attendance, by referral, by advertisements, etc.)

4.1. Exclusion criteria

4.2. Inclusion criteria

5. Trial Procedures

5.1 Good Clinical Practice (GCP)

Important details: (i) the investigator, not the sponsor has the main responsibility, (ii) all physicians involved in recruitment to a trial are investigators, (iii) CV must be supplied for all investigators, (iv) all data must be registered not only in a case report form (CRF) but also in patient records, (v) all data in CRFs must be verifiable, (vi) all data must be stored for at least 15 years

All trials can (should) be monitored by the sponsor and/or external agencies

5.2 Safety Registration

For laboratory data decide before the trial (i) normal limits, (ii) which events that are related to the disease treated (e.g. leukocytosis and CRP increase) and (iii) which values that constitute a serious event

6. Endpoints

7. Analyses

All patients must be analysed - loss of ?% of patients due to ”no data” disqualifies the trial.

7.1 Interim Analyses

7.1 ITT

7.2 PP

8. Ethics

9. Publication

Conclusions

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