Observational Study of Incidence Rates of Esophageal Cancer in Women Taking Medications for the Prevention or Treatment of Osteoporosis (MK-0217A-352)

Study Overview
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Brief Summary
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This is a 2-phase retrospective database study, using both case-cohort and inception (intention-to-treat) cohort analyses to evaluate any association between oral treatments for osteoporosis and the risk of esophageal cancer in women.

Official Title
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The Risk of Esophageal Cancer in Relation to the Treatment and Prevention of Osteoporosis in Women

Conditions
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Esophageal Cancer, Squamous Cell Carcinoma, Adenocarcinoma

Intervention / Treatment
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* Drug: Alendronate
* Drug: Etidronate
* Drug: Ibandronate
* Drug: Risedronate
* Drug: Raloxifene


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cases: Women in the database aged 55 or older between 1996 and 2008 with diagnosis of esophageal cancer Comparator Controls: Each case was matched to all women in the random subcohort of 25,000 who had the same year of birth as the case and were in the database at the time of diagnosis. Exclusion Criteria: Women with diagnosis of any other cancer or Paget's Disease or who have received oral or intravenous steroids before the index date

Ages Eligible for Study
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Minimum Age: 55 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Esophageal Cancer Cases<br>Participants with any United Kingdom General Practice Research Database (GPRD) Medical code for esophageal cancer (cases). Cases were confirmed and case onset dates determined by electronic algorithm (based on electronic medical record data) or by medical record review. | Drug: Alendronate<br> <br> * Other names: FOSAMAX®;Drug: Etidronate<br> <br> * Other names: DIDRONEL®;Drug: Ibandronate<br> <br> * Other names: BONIVA®;Drug: Risedronate<br> <br> * Other names: ATELVIA®;Drug: Raloxifene<br> <br> * Other names: EVISTA®;|
| Comparison Sample (Case-Cohort)<br>Participants who were matched to cases by age and membership in the GPRD on the case's onset date, and had not experienced any form of esophageal cancer or Paget's Disease and had not received oral or intravenous steroids or chemotherapy or radiotherapy, as indicated by GPRD codes. | Drug: Alendronate<br> <br> * Other names: FOSAMAX®;Drug: Etidronate<br> <br> * Other names: DIDRONEL®;Drug: Ibandronate<br> <br> * Other names: BONIVA®;Drug: Risedronate<br> <br> * Other names: ATELVIA®;Drug: Raloxifene<br> <br> * Other names: EVISTA®;|
| Non-treated Comparators<br>Participants who did not initiate treatment of osteoporosis with a study drug | |
| Alendronate<br>Participants initiating treatment for osteoporosis with alendronate | Drug: Alendronate<br> <br> * Other names: FOSAMAX®;|
| Etidronate<br>Participants initiating treatment for osteoporosis with etidronate | Drug: Etidronate<br> <br> * Other names: DIDRONEL®;|
| Ibandronate<br>Participants initiating treatment for osteoporosis with ibandronate | Drug: Ibandronate<br> <br> * Other names: BONIVA®;|
| Risedronate<br>Participants initiating treatment for osteoporosis with risedronate | Drug: Risedronate<br> <br> * Other names: ATELVIA®;|
| Raloxifene<br>Participants initiating treatment for osteoporosis with raloxifene | Drug: Raloxifene<br> <br> * Other names: EVISTA®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Exposure to Study Drugs (Case-Cohort Analysis) | To determine the use of study drugs (alendronate, etidronate, ibandronate, risedronate, and raloxifene) among female participants with esophageal cancer (cases) and a comparison subcohort, a case-cohort analysis was performed using women meeting criteria from the General Practice Research Database (GPRD, United Kingdom). Exposure to osteoporosis drugs administered 720 days before cancer onset was determined in cases and compared to contemporaneous assessments in a comparison subcohort matched by year of birth and membership in the GPRD on the case's onset date. Cases were confirmed and case onset dates determined by electronic algorithm (based on electronic medical record data) or by medical record review. | Exposure to study drug at least 720 days before disease onset | 
| Number of Cases of Esophageal Cancer Per 100,000 Woman-Years (Intent-to-Treat Analysis) | To assess the relative risk of esophageal cancer associated with osteoporosis study drugs (alendronate, etidronate, ibandronate, risedronate, and raloxifene), initiators of osteoporosis drugs and non-initiators (comparators, women sharing match criteria with the initiator) entered an inception cohort for every three-month period, beginning in the first quarter of 1996. Assignment to study drug exposure group remained fixed from the start of follow-up, analogous to an intent-to-treat analysis. The risk of esophageal cancer among initiators of study drug compared to non-initiators of study drug was estimated through calculation of a hazard ratio. For calculation of 721+ day hazard ratios, only esophageal cancer cases occurring at least 721 days from initiation of study drug were used. For calculation of 1441+ day hazard ratios, only esophageal cancer cases occurring at least 1441 days from initiation of study drug were used. | Up to approximately 7.3 years of follow-up |