5–1: Appendix 5–1 Beyond the Basics: Questions to Consider for Critique of Primary Literature

RANDOMIZED CONTROLLED TRIAL

• Refer to Chapter 4, Drug Literature Evaluation I: Controlled Clinical Trial Evaluation

PHARMACOECONOMIC ANALYSIS

• Refer to Chapter 6, Pharmacoeconomics

NONINFERIORITY TRIAL

• Is the reference drug’s efficacy established using adequate historical data and/or addition of a placebo arm?

• Are the participants and outcome measures for the noninferiority similar compared to previous studies that confirmed the efficacy of the reference drug (e.g., constancy assumption)?

• Is the method used to determine the noninferiority (NI) margin predetermined before the study, both clinically and statistically sound, and the reasoning clearly stated in the article?

• Was a per-protocol analysis used? If so, did they also perform an intention-to-treat analysis?

• Was the sample size modified as the study progressed? If so, was a clear explanation of how the blinded information was handled and by what method these modifications were determined also provided?

• Was this study an attempt to rescue a failed superiority trial?

N-OF-1 TRIAL

• Was assignment of active and control treatment to study periods randomized?

• Was the study blinded?

• Were multiple observation periods used?

• Were study endpoints clearly defined?

• Was the washout period between study periods adequate?

ADAPTIVE CLINICAL TRIAL (ACT)

• Are the methodologies used to make adaptive changes in the trial adequately described?

• What logistical issues exist and have they been adequately addressed?

• Are the adaptive changes based on evidence and good clinical judgment?

• Did extensive adaptation to the protocol occur during the study?

• To what extent is intrusion of bias noted?

• Who has access to the information created from interim analyses?

• If the study was stopped early, is the totality of evidence adequate?

STABILITY STUDY

• Were study methodologies and test conditions clearly defined?

• Were validated assays used?

• Were assays validated using time-zero measurements and an adequate number of test samples taken?

BIOEQUIVALENCY STUDY

• Did the protocol define the characteristics of the subjects?

• Were confounding factors (e.g., smoking, alcohol use) identified and controlled?

• Was a crossover design used?

• Was the study randomized and blinded?

PROGRAMMATIC RESEARCH

• Were one of two options used for subject comparison: (1) comparison of subjects to those not using the program or service, (2) comparison of subjects before or after initiation of the program or service?

• Was the program or service clearly defined?

• Did the authors specify from whose perspective (e.g., patient, provider, physician, third-party payer) the study was undertaken?

• If costs were analyzed, were all costs associated with provision of the program or service included in the analysis, including personnel, inflationary changes, and cost savings had the intervention not occurred?

• Were clinically important outcome parameters used to assess effectiveness of the program or service?

COHORT STUDY