Article type
Year
Abstract
Background: Regulatory approval of drugs is often based on trials designed to demonstrate proof of concept. However, such studies are not typically designed to simultaneously demonstrate proof of value in a formulary recommendations setting.
Objectives: To enumerate types of inadequate information in drug submissions which received a 'do not list’ recommendation from the Canadian Expert Drug Advisory Committee (CEDAC).
Methods: CEDAC 'do not list’ recommendations from 2009-2010 were reviewed. Recommendations with cited reasons involving inadequate information were identified, and recorded. A summary of these reasons was compiled.
Results: Of 26 'do not list’ recommendations, a total of 19 (73%) were associated with one or more forms of inadequacy of information. Amongst them, 10/19 (53%) were associated with inadequate evidence of a clinically meaningful benefit compared to either placebo or an active comparator, 9/19 (47%) were associated with a lack of trials versus any active comparator or a particular active comparator of interest, 5/19 (26%) failed to report data for a key outcome measure, 3/19 (16%) used a surrogate outcome considered to be of limited value, and 2/19 (11%) were associated with limited generalizability in terms of the study populations. Table 1 summarizes and highlights variations in the types of information inadequacies that were noted according to the type of evidence used in the submission.
Conclusions: Proof of concept studies don’t always provide sufficient information to show proof of value, and represent a challenge for recommendation panels. In such situations, value judgments play an important role due to uncertainties regarding the information available. Carefully planned trial designs involving relevant comparators, evaluating outcomes relevant to the interests of regulators, physicians and patients, will increase the likelihood of a recommendation for formulary listing.
Objectives: To enumerate types of inadequate information in drug submissions which received a 'do not list’ recommendation from the Canadian Expert Drug Advisory Committee (CEDAC).
Methods: CEDAC 'do not list’ recommendations from 2009-2010 were reviewed. Recommendations with cited reasons involving inadequate information were identified, and recorded. A summary of these reasons was compiled.
Results: Of 26 'do not list’ recommendations, a total of 19 (73%) were associated with one or more forms of inadequacy of information. Amongst them, 10/19 (53%) were associated with inadequate evidence of a clinically meaningful benefit compared to either placebo or an active comparator, 9/19 (47%) were associated with a lack of trials versus any active comparator or a particular active comparator of interest, 5/19 (26%) failed to report data for a key outcome measure, 3/19 (16%) used a surrogate outcome considered to be of limited value, and 2/19 (11%) were associated with limited generalizability in terms of the study populations. Table 1 summarizes and highlights variations in the types of information inadequacies that were noted according to the type of evidence used in the submission.
Conclusions: Proof of concept studies don’t always provide sufficient information to show proof of value, and represent a challenge for recommendation panels. In such situations, value judgments play an important role due to uncertainties regarding the information available. Carefully planned trial designs involving relevant comparators, evaluating outcomes relevant to the interests of regulators, physicians and patients, will increase the likelihood of a recommendation for formulary listing.