Radiologic correlates of symptom-based diagnostic criteria for chronic rhinosinusitis.

OBJECTIVE: In 1997, the Task Force on Rhinosinusitis (TFR) set forth symptom-based diagnostic guidelines for chronic rhinosinusitis (CRS). In the present study, we examined radiologic correlates of the TFR diagnostic criteria for rhinosinusitis. STUDY DESIGN AND SETTING: One hundred twenty-five consecutive patients undergoing computed tomography (CT) scans of the sinuses were studied at Oregon Health and Science University. Patients were evaluated prospectively with a questionnaire based on the TFR criteria, and their CT scans were graded according to the Lund-Mackay scoring system. RESULTS: Of the 125 patients, 115 met the symptom criteria for CRS. However, 40 of 115 had negative scans (Lund-McKay score, 0) despite meeting the diagnostic criteria for rhinosinusitis. Of 115, 75 had positive scans (Lund-McKay score, >1). Of the 10 patients who had negative diagnoses for rhinosinusitis, 9 had a positive CT scan. The Kappa coefficient was -0.103 (+/-95% confidence interval, -0.201 to -0.004), indicating poor agreement between CRS positivity and CT positivity. The sensitivity of TFR criteria for detecting a positive scan was 89%, but the specificity was poor at only 2%. CONCLUSION AND SIGNIFICANCE: Based on these pilot data, it appears that the specificity and predictive value of the current TFR criteria may not be adequate to serve as a diagnostic standard for rhinosinusitis. Additional validating data may provide guidance for improving the sensitivity and specificity of symptom-based diagnostic instruments for rhinosinusitis.

Challenges and opportunities in establishing scientific and regulatory standards for determining therapeutic equivalence of modified-release products: Workshop summary report.

BACKGROUND: Modified-release (MR) products are complex dosage forms designed to release drug in a controlled manner to achieve the desired efficacy and safety profiles. Inappropriate control of drug release from such products may result in reduced efficacy or increased toxicity. OBJECTIVE: This paper is a summary report of the American Association of Pharmaceutical Scientists, International Pharmaceutical Federation, and Product Quality Research Institute workshop titled "Challenges and Opportunities in Establishing Scientific and Regulatory Standards for Assuring Therapeutic Equivalence of Modified Release Products", held October 1-2, 2009, in Baltimore, Maryland. METHODS: The workshop provided an opportunity for pharmaceutical scientists from academia, industry, and regulatory agencies to discuss current regulatory expectations and industry practices for evaluating the pharmaceutical equivalence and bioequivalence of oral MR products. RESULTS: In the case of conventional monophasic MR formulations, the current regulatory approaches and criteria for bioequivalence evaluation were considered adequate for the assessment of therapeutic equivalence and inter-changeability of drug products. Additional measures may occasionally be needed to determine the bioequivalence of multiphasic MR products. The metric of partial AUC proposed by the US Food and Drug Administration received broad support as an additional measure for evaluating bioequivalence of multiphasic MR products designed to have a rapid onset of drug action followed by sustained response. The cutoff for partial AUCs may be based on the pharmacokinetic/pharmacodynamic or pharmacokinetic/ response characteristics of the products under examination. If the new metric is highly variable, the bioequivalence limits may be set based on the known within-subject variability for the reference product. CONCLUSIONS: The current regulatory approaches and criteria for bioequivalence evaluation were considered adequate for the assessment of therapeutic equivalence and interchangeability of conventional monophasic MR products. Additional measures may occasionally be needed to establish the bioequivalence of multiphasic MR products, and development of such measures is an important objective. The metric of partial AUC was proposed for products designed to have a rapid drug action followed by sustained response.

Challenges and opportunities in establishing scientific and regulatory standards for assuring therapeutic equivalence of modified release products: workshop summary report.

Modified release products are complex dosage forms designed to release drug in a controlled manner to achieve desired efficacy and safety. Inappropriate control of drug release from such products may result in reduced efficacy or increased toxicity. This workshop provided an opportunity for pharmaceutical scientists from academia, industry, and regulatory agencies to discuss current industry practices and regulatory expectations for demonstrating pharmaceutical equivalence and bioequivalence of MR products, further facilitating the establishment of regulatory standards for ensuring therapeutic equivalence of these products.

Challenges and opportunities in establishing scientific and regulatory standards for assuring therapeutic equivalence of modified-release products: workshop summary report.

Modified-release products are complex dosage forms designed to release drug in a controlled manner to achieve desired efficacy and safety. Inappropriate control of drug release from such products may result in reduced efficacy or increased toxicity. This workshop provided an opportunity for pharmaceutical scientists from academia, industry and regulatory agencies to discuss current regulatory expectations and industry practices for demonstrating pharmaceutical equivalence and bioequivalence of MR products, further facilitating the establishment of regulatory standards for ensuring therapeutic equivalence of these products.