Criteria	Good (meet all criteria)	Fair	Poor (has one or more)
Design	Crossover design (or parallel design with appropriate justification)	Parallel design
Sample Size	Cross-over n≥12; if parallel design, n should be higher	n is 8–12	n<8
Exposure	Clear definition of exposure (clearly defined drug(s), dosages, and frequency). Clearly stated exposure assessment accounting for ensured exposure to drug (in d-d-I studies, exposure to both drugs clearly defined).	Clear definition of exposure. Adequate but less than ideal exposure assessment (self-report alone).	Exposure not defined. No exposure assessment.
Outcome	Appropriate PK parameter mea sured for desired outcome (e.g., for hormonal contraception Cmax, AUC or Cavg.; for non-oral formulation C average or AUC) and the measured out come has clinically meaningful relevance (known or theoretical).	PK parameter less than ideal but still give some potentially useful information.	Clinically irrelevant PK parameter.
Timing	Time of the blood draw(s)/testing appropriate for the desired outcome. Repeated measures taken (unless steady state demonstrated to be achieved, then one-time measurement OK).	Time of blood draw not ideal but still yields useful information. One-time measurements.	Time of blood draw out of range to yield meaningful information in relation to desired outcome.
Intersubjective variability	Methods minimize possibility for intersubjective variability. (e.g., range of timing for blood draws). There is adequate control in studies for factors known to impact metabolism (age, BMI, other medications, or other known risk factors) as appropriate/needed.	Moderate intersubjective variability. Some controlling for factors known to impact metabolism or no theoretical factors known to impact so no controlling done.	Very large intersubjective variability. No control and clear presence of factors that very likely impacted metabolism between subjects.
Population	Appropriate population chosen (e.g., reproductive-aged women).	Less than ideal population but not fatally so.	Completely wrong population chosen that has proven or likely will have different metabolism/effect of the drugs.
Steady state of perpetrator drug (Victim drug OK for one-time dose)	Clearly allowed for perpetrator drug to be in steady state at time of evaluation.	Likely that perpetrator drug was in steady state; however,methods not clearly defined or uncertain of SS actually reached.	Perpetrator drug clearly NOT in steady state.
Assay/analyses and validation	Study described methods for analysis and validation of analyses.	Study did not describe methods for analysis and validation of analyses.	Methods described for analysis or validation described but methods used known to be