Clinical trial NCT01138124: Gabapentin and Risk of Pancreatic Cancer and Renal Cancer (GPRD)
Official title: Risk of Pancreatic Cancer and Renal Cancer in Patients Exposed to Gabapentin in the United Kingdom General Practice Research Database
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Renal Pelvis Cancer
Restless Legs Syndrome
Epilepsy
Neuropathic Pain
Chronic Pancreatitis
Hypertension
Pancreatic Cancer
Diabetes
Renal Cancer
Renal Cell Carcinoma
Keywords: renal cell carcinoma
epidemiology
pancreatic cancer
renal cancer
renal pelvis cancer
GPRD
case-control
Gapabentin
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2010-06-07
Enrollment: 54202
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: RETROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The study cohort from which cases and controls are drawn is all subjects in the UK GPRD 1993-2008. 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. 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. There are several advantages to the GPRD dataset for this study. It is a large dataset with detailed longitudinal prescription data, and long term follow-up (mean 7 years) to allow for latency in carcinogenicity. It provides good representation of the elderly who are disproportionately affected by pancreatic and renal cancers, and routinely includes data recorded by general practitioners on potential risk factors such as smoking and body mass index.

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* The study cohort from which cases and controls are drawn is all subjects in the UK GPRD 1993-2008. 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. 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.

Exclusion Criteria:

* 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.)

Primary outcomes:
measure: Number of Pancreatic Cancer Cases and Matched Controls With the Indicated Exposure to Gabapentin
timeFrame: 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
measure: Number of Pancreatic Cancer Cases and Matched Controls With the Indicated Number of Gabapentin Prescriptions
timeFrame: 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
measure: Number of Pancreatic Cancer Cases and Matched Controls With the Indicated Duration of Exposure to Gabapentin
timeFrame: 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
measure: Number of Pancreatic Cancer Cases and Matched Controls With the Indicated Cumulative Dose of Gabapentin
timeFrame: 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
measure: Number of Renal Cancer Cases and Matched Controls With the Indicated Exposure to Gabapentin
timeFrame: 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.
measure: Number of Renal Cancer Cases and Matched Controls With the Indicated Number of Gabapentin Prescriptions
timeFrame: 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.
measure: Number of Renal Cancer Cases and Matched Controls With the Indicated Duration of Exposure to Gabapentin
timeFrame: 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.
measure: Number of Renal Cancer Cases and Matched Controls With the Indicated Cumulative Dose of Gabapentin
timeFrame: 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.
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: