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Table 1 Description of variables included in the analyses

From: Factors associated with positive and negative recommendations for cancer and non-cancer drugs for rare diseases in Canada

Variable Values Details
Recommendation 0 if negative
1 if positive
• Negative: do not list
• Positive: list, list with conditions, list with criteria, list if price reduced or cost-effectiveness improved
Submission characteristics
Year of recommendation Continuous variable • Year of final recommendation
Type of submission 0 if new submission
1 if resubmission
• Type of submission according to CADTH classification
Presence of RCTs 0 if no
1 if yes
• RCTs were included in the systematic review
Therapeutic class of drugs 0 if alimentary tract & metabolism
1 if Antineoplastic & immunomodulating
2 if other
• Classification of drugs based on ATC codes
Characteristics of disease
Type of condition 0 if cancer
1 if non-cancer
• Classification based on ICD-10
Prevalence 0 if ultra-orphan
1 if orphan
• Ultra-orphan: < 1 in 100,000 people
• Orphan: < 1 in 2000 people
Clinical need 0 if no or not stated
1 if yes
• Need for alternative treatment options, no existing treatment or “unmet need”
Clinical safety/efficacy
Safety issues 0 if yes
1 if no
• Concerns over potential serious life-threatening adverse events or unknown safety profiles
Improvements in biomarker/ surrogate outcome 0 if no, inconsistent or not measured
1 if yes
• Biomarker is “a defined characteristic that is measured as an indicator of normal biological process, pathogenic process, or responses to an exposure or intervention, including therapeutic interventions” [17].
• Surrogate outcome is “an endpoint that is used in clinical trials as a substitute for a direct measure of how a patient feels, functions, or survives” [17].
• Meaningful improvements defined as statistically significant differences or non-inferiority in biomarker/ surrogate outcomes (e.g. weight, 6 min walk test, progression-free survival)
Improvements in clinical outcomes 0 if no, inconsistent or not measured
1 if yes
• Clinical outcome is “an outcome that describes or reflects how an individual feels, functions or survives” [17].
• Meaningful improvements defined as statistically significant differences or non-inferiority in clinical outcomes (e.g. survival, transplantation)
Improvements in PRO 0 if no, inconsistent or not measured
1 if yes
• PRO is “a measurement based on a report that comes directly from the patient about the status of a patient’s health condition without amendment or interpretation of the patient’s response by a clinician or anyone else” [17].
• Meaningful improvements defined as statistically significant differences or non-inferiority in PRO (e.g. QOL, rating of pain intensity, SF-36)
Quality of evidence
Availability of comparative data 0 if no
1 if yes
• Based on availability of direct head-to-head comparative studies (where comparators were available)
Consistency between population in trials and indications 0 if no
1 if yes
• Present when ‘final recommendation’ document stated that data from trials included all subgroup of the indicated population
• Not present when for example submitted indication includes mild, moderate, and severe forms of disease but trial data limited to mild-moderate forms of disease
Bias in outcome measures 0 if yes
1 if no
• Present when indicated in the final recommendation document
• Bias in outcome measurements (e.g., subjective outcomes classified by non-blinded investigators)
Long term data 0 if no
1 if yes
• Presence of long-term data where long-term data is important given the course of disease
• Present when indicated in the final recommendation document
Other study design issues 0 if yes
1 if no
• Concerns over other aspects of study design (e.g., small sample size, carry-over effects associated with withdrawal trial methodology)
• Present when indicated in the final recommendation document
Cost/ cost-effectiveness
Daily treatment cost Continuous variable in $CDN/ patient • Average daily treatment cost of drugs per patient
ICER Continuous variable in $CDN/QALY • ICER calculated by CADTH or by manufacturer if no ICER calculated by CADTH was available
  1. ATC Anatomical Therapeutic Chemical (ATC) Classification System, CADTH Canadian Agency for Drugs and Technologies in Health, ICD International Classification of Disease, ICER Incremental Cost-effectiveness Ratio, ICU Intensive Care Unit, PRO Patient- reported Outcome, QALY Quality-adjusted Life Years, QOL Quality of Life, RCT Randomized Controlled Trial