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

NCT01077817 | Completed Results

• 3 other identifiers: 0217A-352EP02001.0292010_015
• Study Type: observational
• Target: 684,815
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Esophageal Cancer; Squamous Cell Carcinoma; Adenocarcinoma

Outcome Measures

Primary Outcomes (2)

• 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

Study Arms (8)

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.

Drug: Alendronate; Drug: Etidronate; Drug: Ibandronate; Drug: Risedronate; Drug: Raloxifene

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.

Drug: Alendronate; Drug: Etidronate; Drug: Ibandronate; Drug: Risedronate; Drug: Raloxifene

Non-treated Comparators

Participants who did not initiate treatment of osteoporosis with a study drug

Alendronate

Participants initiating treatment for osteoporosis with alendronate

Drug: Alendronate

Etidronate

Participants initiating treatment for osteoporosis with etidronate

Drug: Etidronate

Ibandronate

Participants initiating treatment for osteoporosis with ibandronate

Drug: Ibandronate

Risedronate

Participants initiating treatment for osteoporosis with risedronate

Drug: Risedronate

Raloxifene

Participants initiating treatment for osteoporosis with raloxifene

Drug: Raloxifene

Interventions

Alendronate DRUG

Also known as: FOSAMAX®

Alendronate; Comparison Sample (Case-Cohort); Esophageal Cancer Cases

Etidronate DRUG

Also known as: DIDRONEL®

Comparison Sample (Case-Cohort); Esophageal Cancer Cases; Etidronate

Ibandronate DRUG

Also known as: BONIVA®

Comparison Sample (Case-Cohort); Esophageal Cancer Cases; Ibandronate

Risedronate DRUG

Also known as: ACTONEL®, ATELVIA®

Comparison Sample (Case-Cohort); Esophageal Cancer Cases; Risedronate

Raloxifene DRUG

Also known as: EVISTA®

Comparison Sample (Case-Cohort); Esophageal Cancer Cases; Raloxifene

Eligibility Criteria

• Age: 55 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

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).

You may qualify if:

• 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.

You may not qualify if:

• Women with diagnosis of any other cancer or Paget's Disease or who have received oral or intravenous steroids before the index date

Sponsors & Collaborators

• Organon and Co: lead
• World Health Information Science Consultants, LLC: collaborator

Related Links

• EUPAS Register (EUPAS17909)

MeSH Terms

Conditions

Esophageal Neoplasms; Carcinoma, Squamous Cell; Adenocarcinoma

Interventions

Alendronate; Etidronic Acid; Ibandronic Acid; Risedronic Acid; Raloxifene Hydrochloride

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Squamous Cell

Intervention Hierarchy (Ancestors)

Diphosphonates; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tamoxifen; Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Alec Walker, MD, DrPH

  World Health Information Science Consultants, LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 26, 2010
• First Posted: March 1, 2010
• Study Start: February 26, 2010
• Primary Completion: February 16, 2012
• Study Completion: February 16, 2012
• Last Updated: February 3, 2022
• Results First Posted: May 1, 2013

Record last verified: 2022-02