Chapter Four: Drug Literature Evaluation I: Controlled Clinical Trial Evaluation

Learning Objectives

After completing this chapter, the reader will be able to:

• Identify skills health care practitioners need to evaluate medical literature and apply it to patient care.

• Describe special characteristics of a controlled clinical trial that distinguish this research design as the prototype for clinical research.

• Prepare a null hypothesis (H₀) based upon the clinical trial objective(s) and endpoint(s).

• Differentiate between the types of data, measures of central tendency, and measures of variability.

• Differentiate between Type I and Type II errors; discuss methods to reduce the possibility of either of these errors occurring.

• Interpret p values and 95% confidence interval (CI); discuss whether to reject or fail-to-reject the H₀ by using these clinical trial results.

• Calculate and interpret relative risk (RR), relative risk reduction (RRR), absolute risk reduction (ARR), and number needed to treat (NNT).

• State whether statistical significance and clinical difference are present using the clinical trial results.

• Explain the purpose and usage of editorials, letters to the editor, and secondary journals in critiquing clinical trials and the application of results into practice.

• Identify key features of adaptive clinical trials and noninferiority trials.

Key Concepts

• Practitioners need to be able to efficiently locate, critically analyze, and effectively communicate data from the primary literature to patients, other health care professionals, and the public.

• A controlled clinical trial is the gold-standard study design to measure and quantify effect differences between an intervention and a control.

• The entire published study should be read and thoroughly evaluated; decision-making should not rely solely on reading abstracts.

• The results of a controlled clinical trial should be extrapolated to the type of patient enrolled in the study, and readers should be aware of the limitations of surrogate endpoints and subgroup analyses.

• Randomization is an essential component of all controlled clinical trials that significantly differentiates them from other study designs.

• The controlled clinical trial primary endpoint should be appropriate for the study purpose and measured using valid techniques and methods.

• An appropriate sample size in a controlled clinical trial is vital for the study results to have any significant meaning; conducting a power analysis is important to determine a suitable sample size.

• Correctly interpreting p values is crucial to evaluating a controlled clinical trial; not all statistically significant p values are clinically important. The magnitude of difference in effect between the intervention and control cannot be determined with the p value.

• The use of 95% CI can assist the reader in assessing the magnitude of difference in effect between the intervention and control.

• Calculating measures of association (RR, ARR, RRR, NNT) for nominal data provides further information to interpret controlled clinical trial results

• Nonstatistically significant results do not equate to the intervention and control being the same or equal.

• All controlled clinical trial results need to be assessed to determine the clinical relevance of the intervention versus control.

• Controlled clinical trial investigators and ...