Numerous studies have directly assessed patient preferences for different treatments, but have provided little evidence supporting the validity of their preference questionnaires. OBJECTIVE: The objective of this study was to perform a qualitative analysis of patients' perspectives of an Osteoporosis Treatment Preference Questionnaire (OTPQ) comparing preferences for once-monthly versus once-weekly administration of bisphosphonate therapy for osteoporosis. METHODS: The OTPQ contains one question directly eliciting dosing schedule preference, two questions with multiple items assessing possible reasons for the stated preferences, and a convenience question. Because the OTPQ comprises no multi-item scales and thus psychometric evaluation analyses would be limited, a cognitive debriefing study was conducted as the primary method of assessing validity. This study involved semi-structured one-on-one telephone interviews with a convenience sample of women currently receiving bisphosphonate therapy for postmenopausal osteoporosis. They completed the OTPQ at the beginning of the phone call and subsequently were interviewed about the mental process involved in responding to the questions, their interpretation of the items, and how responses were selected. RESULTS: Twenty women completed the interviews. The participants were primarily white (85%), had a mean age of 63.7 years, and most were taking weekly alendronate (85%). In general, participants believed that the OTPQ was easy to understand and appropriate for assessing patient preferences for once-monthly versus once-weekly osteoporosis treatment. One item was not interpreted in a consistent manner among 9 of the first 15 participants. As a result, this item was revised and tested with the remaining five participants. These additional interviews affirmed that the revision clarified the intent of the item. No additional modifications to the questionnaire were required based on the findings. CONCLUSIONS: This cognitive debriefing study provided a strong foundation for the content validity of the OTPQ. Such studies should be a critical component in the development of preference questionnaires.