Ignite Creation Date:
2024-05-06 @ 7:06 AM
Last Modification Date:
2024-10-26 @ 11:45 AM
Study NCT ID:
NCT02475499
Status:
COMPLETED
Last Update Posted:
2016-03-14
First Post:
2015-06-16
Brief Title:
Incretin-based Drugs and Pancreatic Cancer
Sponsor:
Canadian Network for Observational Drug Effect Studies CNODES
Organization:
Canadian Network for Observational Drug Effect Studies CNODES
Study Overview
Official Title:
The Use of Incretin-based Drugs and the Risk of Pancreatic Cancer in Patients With Type 2 Diabetes
Status:
COMPLETED
Status Verified Date:
2016-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The purpose of this study is to determine whether incretin-based drugs used to treat type 2 diabetes taken either alone in or combination with other anti-diabetic drugs are associated with an increased risk of pancreatic cancer PC compared to sulfonylureas
The investigators will carry out separate population based cohort studies using administrative health databases in five jurisdictions in Canada the US and the UK Cohorts will be defined by the initiation of a new anti-diabetic drug when incretin-based drugs entered the market with follow-up until hospitalization for PC The results from the separate sites will be combined to provide an overall assessment of the risk of PC in users of incretin-based drugs and by class of incretin-based drugs
The investigators will carry out separate population based cohort studies using administrative health databases in five jurisdictions in Canada the US and the UK Cohorts will be defined by the initiation of a new anti-diabetic drug when incretin-based drugs entered the market with follow-up until hospitalization for PC The results from the separate sites will be combined to provide an overall assessment of the risk of PC in users of incretin-based drugs and by class of incretin-based drugs
Detailed Description:
The study objective is to determine whether the use of incretin-based drugs compared with the use of sulfonylureas is associated with an increased risk of pancreatic cancer PC in routine clinical practice The investigators will use a common-protocol approach to conduct retrospective cohort studies using administrative health care data from five jurisdictions the Canadian provinces of Alberta Manitoba and Ontario as well as United States US MarketScan and the United Kingdom UK Clinical Practice Research Datalink CPRD Briefly the Canadian databases include population-level data on physician billing diagnoses and procedures from hospital discharge abstracts and dispensations for prescription drugs Ontario data will be restricted to patients aged 65 years and older as prescription data are not available for younger patients The CPRD is a clinical database that is representative of the UK population and contains the records for patients seen at over 680 general practitioner practices in the UK these data will be linked to the Hospital Episode Statistics HES database which contains in-hospital diagnosis and procedure data US MarketScan includes individuals and their dependents covered by large US employer health insurance plans and government and public organizations
Study population
In each jurisdiction the investigators will assemble a base cohort that includes all patients with a first-ever prescription for a non-insulin anti-diabetic drug including biguanides sulfonylureas thiazolidinediones DPP-4 inhibitors GLP-1 analogs alpha-glucosidase inhibitors meglitinides or combinations of these drugs from the earliest availability of data at each site to the last date of availability of data The date of prescription for the CPRD or dispensation for all other sites of the first-ever non-insulin anti-diabetic drug will define the date of base cohort entry From this base cohort a study cohort will be created including all patients who initiated a new anti-diabetic drug class during the year in which incretin-based drugs entered the market in each jurisdiction or any time thereafter These new users consist of both those who are newly-treated for diabetes as well as those who switch to or add on a new anti-diabetic drug class not included as part of their previous treatment history The date of study cohort entry is defined by the prescription date of the newly-prescribed drug class Patients in the study cohort will be followed from the date of study cohort entry 365 days until an event defined below or censoring due to death departure from the database loss of continuous health plan or drug plan enrolment entry into a long-term care facility or the end of the study period June 30 2014 or the last date of data availability at that site whichever occurs first
Case-control selection
The cohort defined above will be analyzed using a nested case-control analysis where cases are defined as a hospitalization for PC Risk set sampling will be used to randomly select up to 20 controls for each case matched on sex age 365 days date of study cohort entry 180 days duration of treated diabetes 90 days and duration of follow-up in days
Exposure assessment
Ever-use of an anti-diabetic drug will be defined as any prescription for an anti-diabetic agent between base cohort entry and the index day -365 days This 365-day lag period will be applied to account for disease latency and potential protopathic bias by only considering prescriptions received from and including the Base Cohort Entry Date until and including the date one year prior to the Index day Ever-use of exposure will be classified hierarchically based on the following three mutually-exclusive categories 1 incretin-based drugs 2 sulfonylureas 3 other antidiabetic agents Sulfonylureas will serve as the primary reference category as incretin-based drugs are second- to third-line therapy and thus used at a comparable point in the disease management
Statistical analyses
Conditional logistic regression will be used to estimate odds ratios ORs and corresponding 95 confidence intervals CIs of the association of hospitalization for PC comparing ever-use of incretin-based drugs to ever-use of sulfonylureas This is considered the primary analysis Secondary analyses will include sub-classifying ever-users of incretin-based drugs by type ie DPP-4 inhibitor vs GLP-1 analog cumulative duration of ever-use 365 days 366-729 days and 730 days and time since initiation of treatment among ever-users In addition four sensitivity analyses will be conducted all defined a priori to assess the robustness of the results Finally all site-specific estimates will be meta-analyzed using random-effects models with inverse variance weighting with fixed-effects analyses conducted as sensitivity analyses The amount of between-site heterogeneity will be estimated using the I square statistic
Study population
In each jurisdiction the investigators will assemble a base cohort that includes all patients with a first-ever prescription for a non-insulin anti-diabetic drug including biguanides sulfonylureas thiazolidinediones DPP-4 inhibitors GLP-1 analogs alpha-glucosidase inhibitors meglitinides or combinations of these drugs from the earliest availability of data at each site to the last date of availability of data The date of prescription for the CPRD or dispensation for all other sites of the first-ever non-insulin anti-diabetic drug will define the date of base cohort entry From this base cohort a study cohort will be created including all patients who initiated a new anti-diabetic drug class during the year in which incretin-based drugs entered the market in each jurisdiction or any time thereafter These new users consist of both those who are newly-treated for diabetes as well as those who switch to or add on a new anti-diabetic drug class not included as part of their previous treatment history The date of study cohort entry is defined by the prescription date of the newly-prescribed drug class Patients in the study cohort will be followed from the date of study cohort entry 365 days until an event defined below or censoring due to death departure from the database loss of continuous health plan or drug plan enrolment entry into a long-term care facility or the end of the study period June 30 2014 or the last date of data availability at that site whichever occurs first
Case-control selection
The cohort defined above will be analyzed using a nested case-control analysis where cases are defined as a hospitalization for PC Risk set sampling will be used to randomly select up to 20 controls for each case matched on sex age 365 days date of study cohort entry 180 days duration of treated diabetes 90 days and duration of follow-up in days
Exposure assessment
Ever-use of an anti-diabetic drug will be defined as any prescription for an anti-diabetic agent between base cohort entry and the index day -365 days This 365-day lag period will be applied to account for disease latency and potential protopathic bias by only considering prescriptions received from and including the Base Cohort Entry Date until and including the date one year prior to the Index day Ever-use of exposure will be classified hierarchically based on the following three mutually-exclusive categories 1 incretin-based drugs 2 sulfonylureas 3 other antidiabetic agents Sulfonylureas will serve as the primary reference category as incretin-based drugs are second- to third-line therapy and thus used at a comparable point in the disease management
Statistical analyses
Conditional logistic regression will be used to estimate odds ratios ORs and corresponding 95 confidence intervals CIs of the association of hospitalization for PC comparing ever-use of incretin-based drugs to ever-use of sulfonylureas This is considered the primary analysis Secondary analyses will include sub-classifying ever-users of incretin-based drugs by type ie DPP-4 inhibitor vs GLP-1 analog cumulative duration of ever-use 365 days 366-729 days and 730 days and time since initiation of treatment among ever-users In addition four sensitivity analyses will be conducted all defined a priori to assess the robustness of the results Finally all site-specific estimates will be meta-analyzed using random-effects models with inverse variance weighting with fixed-effects analyses conducted as sensitivity analyses The amount of between-site heterogeneity will be estimated using the I square statistic
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None