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| ID | Type | Description | Link |
|---|---|---|---|
| EP02001.029 | Other Identifier | Merck | |
| 2010_015 | Other Identifier | Merck |
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| Name | Class |
|---|---|
| World Health Information Science Consultants, LLC | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Esophageal Cancer Cases | 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. |
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| Comparison Sample (Case-Cohort) | 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. |
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| Non-treated Comparators | Participants who did not initiate treatment of osteoporosis with a study drug | ||
| Alendronate | Participants initiating treatment for osteoporosis with alendronate |
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| Etidronate | Participants initiating treatment for osteoporosis with etidronate |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Alendronate | Drug |
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| 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 |
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Inclusion Criteria:
Cases:
Comparator Controls:
Exclusion Criteria:
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Women who have at least two years of experience in the GPRD and are 55 or older between 1996 and 2008; all cases of esophageal cancer were identified and matched to all women in the comparison sample (all women with same year of birth drawn from the random subsample of 25,000).
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| Name | Affiliation | Role |
|---|---|---|
| Alec Walker, MD, DrPH | World Health Information Science Consultants, LLC | Study Director |
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| Label | URL |
|---|---|
| EUPAS Register (EUPAS17909) | View source |
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684,815 women in the General Practice Research Database (GPRD) formed the Overall Study Population. These women met the demographic criteria of being age 55 or older, were born between 1922 and 1955, had more than 720 days experience in the GPRD and at least one of those days fell between 1996 and 2008.
Participants were not recruited nor enrolled in this study. This study is a retrospective observational study. Data from the GPRD were anonymized and used to develop participant cohorts. All diagnoses and treatments were recorded in the course of routine medical practice.
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| ID | Title | Description |
|---|---|---|
| FG000 | Overall Study Population |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Ibandronate | Participants initiating treatment for osteoporosis with ibandronate |
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| Risedronate | Participants initiating treatment for osteoporosis with risedronate |
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| Raloxifene | Participants initiating treatment for osteoporosis with raloxifene |
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| Etidronate | Drug |
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| Ibandronate | Drug |
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| Risedronate | Drug |
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| Raloxifene | Drug |
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| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Overall Study Population |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Number | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | 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. | Case-Cohort analysis population came from the Overall Study Population and comprised 929 women with esophageal cancer (cases) and a Comparison Sample of 338,911 matched control women. Participants may have been exposed to more than one study drug. Also, one comparator may have been used for multiple study drugs. | Posted | Number | Percentage of participants | Exposure to study drug at least 720 days before disease onset |
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| Primary | 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. | Inception Cohort came from the Overall Study Population beginning treatment with an osteoporosis study drug (initiators, 78,630 women) and 300,610 matched control women, who did not receive study drug (noninitiators). Participants may have been exposed to more than one study drug. Also, one comparator may have been used for multiple study drugs. | Posted | Number | Number of cases per 100,0000 woman-years | Up to approximately 7.3 years of follow-up |
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Adverse events were not collected during this study.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Overall Study Population | 0 | 0 | 0 | 0 |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme Corp | 1-800-672-6372 | ClinicalTrialsDisclosure@merck.com |
| ID | Term |
|---|---|
| D004938 | Esophageal Neoplasms |
| D002294 | Carcinoma, Squamous Cell |
| D000230 | Adenocarcinoma |
| ID | Term |
|---|---|
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D006258 | Head and Neck Neoplasms |
| D004066 | Digestive System Diseases |
| D004935 | Esophageal Diseases |
| D005767 | Gastrointestinal Diseases |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D018307 | Neoplasms, Squamous Cell |
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| ID | Term |
|---|---|
| D019386 | Alendronate |
| D012968 | Etidronic Acid |
| D000077557 | Ibandronic Acid |
| D000068296 | Risedronic Acid |
| D020849 | Raloxifene Hydrochloride |
| ID | Term |
|---|---|
| D004164 | Diphosphonates |
| D063065 | Organophosphonates |
| D009943 | Organophosphorus Compounds |
| D009930 | Organic Chemicals |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D013629 | Tamoxifen |
| D013267 | Stilbenes |
| D001597 | Benzylidene Compounds |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
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| Ibandronate |
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| Risedronate |
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| Raloxifene |
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| A hazard ratio estimate was calculated from the case-control matched set to measure the risk association between exposure to etidronate treatment and incidence of esophageal cancer. | Logistic Regression Model | The case-cohort hazard ratio estimate for drug exposure was based on analysis of all cases of esophageal cancer and their comparison sample. | Hazard Ratio (HR) | 1.3 | 2-Sided | 95 | 0.9 | 2.0 | Superiority or Other (legacy) |
| A hazard ratio estimate was calculated from the case-control matched set to measure the risk association between exposure to ibandronate treatment and incidence of esophageal cancer. | Logistic Regression Model | The case-cohort hazard ratio estimate for drug exposure was based on analysis of all cases of esophageal cancer and their comparison sample. | Hazard Ratio (HR) | 4.9 | 2-Sided | 95 | 1.4 | 16.7 | Superiority or Other (legacy) |
| A hazard ratio estimate was calculated from the case-control matched set to measure the risk association between exposure to risedronate treatment and incidence of esophageal cancer. | Logistic Regression Model | The case-cohort hazard ratio estimate for drug exposure was based on analysis of all cases of esophageal cancer and their comparison sample. | Hazard Ratio (HR) | 1.6 | 2-Sided | 95 | 1.0 | 2.5 | Superiority or Other (legacy) |
| A hazard ratio estimate was calculated from the case-control matched set to measure the risk association between exposure to raloxifene treatment and incidence of esophageal cancer. | Logistic Regression Model | The case-cohort hazard ratio estimate for drug exposure was based on analysis of all cases of esophageal cancer and their comparison sample. | Hazard Ratio (HR) | 0.7 | 2-Sided | 95 | 0.2 | 2.2 | Superiority or Other (legacy) |
| Alendronate |
Participants who initiated osteoporosis treatment with alendronate |
| OG002 | Etidronate | Participants who initiated osteoporosis treatment with etidronate |
| OG003 | Ibandronate | Participants who initiated osteoporosis treatment with ibandronate |
| OG004 | Risendronate | Participants who initiated osteoporosis treatment with risedronate |
| OG005 | Raloxifene | Participants who initiated osteoporosis treatment with raloxifene |
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