Risk of Pancreatic Cancer and Renal Cancer in Patients Exposed to Gabapentin in the United Kingdom General Practice Research Database
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 54,202
- 主要终点
- Number of Pancreatic Cancer Cases and Matched Controls With the Indicated Exposure to Gabapentin
研究概览
简要总结
High doses of gabapentin are associated with pancreatic acinar cell tumors in rats, but there has been no post marketing pancreatic carcinogenicity signal with gabapentin as reported by spontaneous reports in the Adverse Events Reporting System or in the published literature. In a published case-control screening study of the association of gabapentin with 55 cancers, the only cancer that met the screening criteria for possibly increased cancer risk with gabapentin exposure was renal (including renal pelvis) cancer. This association was judged to be likely due to or substantially accentuated by confounding by cigarette smoking, hypertension, and lifestyle (Cancer Causes Control 2009;20:1821-1835).
The primary objective of this study is to determine whether exposure to gabapentin is associated with an increased risk of developing pancreatic cancer or renal cancer in the United Kingdom (UK) General Practice Research Database (GPRD). Almost all members of the UK population are registered with a General Practice, which centralizes the medical information not only from the general practitioners themselves but also from specialist referrals and hospital attendances. Over 487 General Practices contribute data to the GPRD.
The study cohort from which cases and controls are drawn is all subjects in the GPRD 1993-2008. Gabapentin was approved in the UK in May 1993. Entry into the study cohort begins Jan 1, 1993 for all those who are registered in GPRD before that time, and at the time of registration if later than Jan 1, 1993. Patients with a first diagnosis of the respective cancer 1995-2008 are risk set matched with up to 10 controls within the same General Practice for age at cohort entry (within two years), sex, and year of entry into the study cohort (within one year). For cases, the index date is the date of first diagnosis of the respective cancer. The index date for controls is set as the date at which the follow-up time from cohort entry is the same as the case. The index date is chosen so as to give the control equal follow-up time to that of the case for ascertainment of use of gabapentin. Cases and controls will be required to have at least 2 years of follow-up in the study cohort before their index date. Data on gabapentin prescriptions are obtained for cases and controls from study cohort entry to the index date.
Crude and adjusted odds ratios and 95% confidence intervals (CI) will be produced from conditional logistic regression models, with additional analyses evaluating for latency and dose-response. For pancreatic cancer, covariates are smoking, body mass index, diabetes, epilepsy, neuropathic pain, and chronic pancreatitis. For renal cancer, covariates are smoking, body mass index, diabetes, hypertension, diuretic use, epilepsy, and neuropathic pain.
详细描述
Patients were not recruited for nor enrolled in this study. This study is a retrospective observational study. Data from medical records or insurance claims databases are anonymised and used to develop a patient cohort. All diagnoses and treatment are recorded in the course of routine medical practice. Actual number of patients could be less than , as it is possible for a patient to be represented in more than one of the four arms (See "Participant Flow: Overall Study" Table) because of the risk set sampling.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Retrospective
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The study cohort from which cases and controls are drawn is all subjects in the UK GPRD 1993-
- •Entry into the study cohort begins Jan 1, 1993 for all those who are registered in GPRD before that time, and at the time of registration if later than Jan 1,
- •Follow-up ends Dec 31, 2008, or earlier if the respective cancer is diagnosed, or if the subject leaves the GPRD for any reason including death.
排除标准
- •Cases and controls will be required to have at least 2 years of follow-up in the study cohort before their index date (For cases, the index date is the date of first diagnosis of the respective cancer. The index date for controls is set as the date at which the follow-up time from cohort entry is the same as the case.)
研究组 & 干预措施
UK GPRD 1993-2008
The study cohort from which cases and controls are drawn is all subjects in the United Kingdom (UK) General Practice Research Database (GPRD) 1993-2008. Each member of the UK population is registered with a General Practice, which centralizes the medical information not only from the general practitioners themselves but also from specialist referrals and hospital attendances. Over 487 General Practices contribute data to the GPRD. Entry into the study cohort begins Jan 1, 1993 for all those who are registered in GPRD before that time, and at the time of registration if later than Jan 1, 1993.
干预措施: Gabapentin prescriptions (Drug)
结局指标
主要结局
Number of Pancreatic Cancer Cases and Matched Controls With the Indicated Exposure to Gabapentin
时间窗: The case index date (ID) was the date of incident pancreatic cancer diagnosis ascertained in the GPRD study cohort 1995-2008. The matched control ID was the date at which the follow-up time from his/her cohort entry was the same as that for the case
Incident pancreatic cancer. Gabapentin Exposure Description: Without 2 year lag = Gabapentin prescription from cohort entry to index date. With 2 year lag = Gabapentin prescription from cohort entry to 2 years prior to index date (to control for prediagnostic prescribing for pain symptoms possibly related to cancer).
Number of Pancreatic Cancer Cases and Matched Controls With the Indicated Duration of Exposure to Gabapentin
时间窗: The case index date (ID) was the date of incident pancreatic cancer diagnosis ascertained in the GPRD study cohort 1995-2008. The matched control ID was the date at which the follow-up time from his/her cohort entry was the same as that for the case
Incident pancreatic cancer. Gabapentin Exposure Description: Without 2 year lag = Gabapentin exposure from cohort entry to index date. With 2 year lag = Gabapentin exposure from cohort entry to 2 years prior to index date (to control for prediagnostic prescribing for pain symptoms possibly related to cancer). Tertile's without 2 year lag: Tertile 1 (0.01 - 1.55 months), Tertile 2 (1.56 - 6.44 months), and Tertile 3 (6.45 - 78.36 months). Tertile's with 2 year lag: Tertile 1 (0.01 - 1.78 months), Tertile 2 (1.79 - 7.20 months), and Tertile 3 (7.21 - 64.13 months).
Number of Pancreatic Cancer Cases and Matched Controls With the Indicated Number of Gabapentin Prescriptions
时间窗: The case index date (ID) was the date of incident pancreatic cancer diagnosis ascertained in the GPRD study cohort 1995-2008. The matched control ID was the date at which the follow-up time from his/her cohort entry was the same as that for the case
Incident pancreatic cancer. Gabapentin Exposure Description: Without 2 year lag = Gabapentin exposure from cohort entry to index date. With 2 year lag = Gabapentin exposure from cohort entry to 2 years prior to index date (to control for prediagnostic prescribing for pain symptoms possibly related to cancer). Tertiles without 2 year lag: Tertile 1 (1-2 prescriptions),Tertile 2 (3-8 prescriptions), and Tertile 3 (9-218 prescriptions). Tertile's with 2 year lag: Tertile 1 (1-2 prescriptions), Tertile 2 (3-10 prescriptions),Tertile 3 (11-191 prescriptions).
Number of Pancreatic Cancer Cases and Matched Controls With the Indicated Cumulative Dose of Gabapentin
时间窗: The case index date (ID) was the date of incident pancreatic cancer diagnosis ascertained in the GPRD study cohort 1995-2008. The matched control ID was the date at which the follow-up time from his/her cohort entry was the same as that for the case
Incident pancreatic cancer. Gabapentin Exposure Description: Without 2 year lag = Gabapentin exposure from cohort entry to index date. With 2 year lag = Gabapentin exposure from cohort entry to 2 years prior to index date (to control for prediagnostic prescribing for pain symptoms possibly related to cancer). Tertile's without 2 year lag: Tertile 1 (0.01 - 33.6 grams), Tertile 2 (33.7 - 185.0 grams), and Tertile 3 (185.1 - 7500.2 grams). Tertile's with 2 year lag: Tertile 1 (0.01 - 39.0 grams), Tertile 2 (39.1 - 210.0 grams), and Tertile 3 (210.1 - 5623.8 grams).
Number of Renal Cancer Cases and Matched Controls With the Indicated Exposure to Gabapentin
时间窗: The case index date (ID) was the date of incident renal cancer diagnosis ascertained in the GPRD study cohort 1995-2008. The matched control ID was the date at which the follow-up time from his/her cohort entry was the same as that for the case.
Incident renal cancer. Gabapentin Exposure Description: Without 2 year lag = Gabapentin prescription from cohort entry to index date. With 2 year lag = Gabapentin prescription from cohort entry to 2 years prior to index date (to control for prediagnostic prescribing for pain symptoms possibly related to cancer).
Number of Renal Cancer Cases and Matched Controls With the Indicated Number of Gabapentin Prescriptions
时间窗: The case index date (ID) was the date of incident renal cancer diagnosis ascertained in the GPRD study cohort 1995-2008. The matched control ID was the date at which the follow-up time from his/her cohort entry was the same as that for the case.
Incident renal cancer. Gabapentin Exposure Description: Without 2 year lag = Gabapentin exposure from cohort entry to index date. With 2 year lag = Gabapentin exposure from cohort entry to 2 years prior to index date (to control for prediagnostic prescribing for pain symptoms possibly related to cancer). Tertiles without 2 year lag: Tertile 1 (1-2 prescriptions),Tertile 2 (3-8 prescriptions), and Tertile 3 (9-218 prescriptions). Tertile's with 2 year lag: Tertile 1 (1-2 prescriptions), Tertile 2 (3-10 prescriptions),Tertile 3 (11-191 prescriptions).
Number of Renal Cancer Cases and Matched Controls With the Indicated Duration of Exposure to Gabapentin
时间窗: The case index date (ID) was the date of incident renal cancer diagnosis ascertained in the GPRD study cohort 1995-2008. The matched control ID was the date at which the follow-up time from his/her cohort entry was the same as that for the case.
Incident renal cancer. Gabapentin Exposure Description: Without 2 year lag = Gabapentin exposure from cohort entry to index date. With 2 year lag = Gabapentin exposure from cohort entry to 2 years prior to index date (to control for prediagnostic prescribing for pain symptoms possibly related to cancer). Tertile's without 2 year lag: Tertile 1 (0.01 - 1.55 months), Tertile 2 (1.56 - 6.44 months), and Tertile 3 (6.45 - 78.36 months). Tertile's with 2 year lag: Tertile 1 (0.01 - 1.78 months), Tertile 2 (1.79 - 7.20 months), and Tertile 3 (7.21 - 64.13 months).
Number of Renal Cancer Cases and Matched Controls With the Indicated Cumulative Dose of Gabapentin
时间窗: The case index date (ID) was the date of incident renal cancer diagnosis ascertained in the GPRD study cohort 1995-2008. The matched control ID was the date at which the follow-up time from his/her cohort entry was the same as that for the case.
Incident renal cancer. Gabapentin Exposure Description: Without 2 year lag = Gabapentin exposure from cohort entry to index date. With 2 year lag = Gabapentin exposure from cohort entry to 2 years prior to index date (to control for prediagnostic prescribing for pain symptoms possibly related to cancer). Tertile's without 2 year lag: Tertile 1 (0.01 - 33.6 grams), Tertile 2 (33.7 - 185.0 grams), and Tertile 3 (185.1 - 7500.2 grams). Tertile's with 2 year lag: Tertile 1 (0.01 - 39.0 grams), Tertile 2 (39.1 - 210.0 grams), and Tertile 3 (210.1 - 5623.8 grams).
次要结局
未报告次要终点