TY - JOUR
KW - Acute Disease
KW - Brain Ischemia
KW - Consumer Product Safety
KW - Databases, Factual
KW - Drug Monitoring/methods
KW - Drug Toxicity
KW - Electronic Health Records
KW - Family Practice/trends
KW - Feasibility Studies
KW - Fibrinolytic Agents/pharmacology
KW - Forecasting
KW - Great Britain
KW - Humans
KW - Hypoglycemic Agents
KW - Longitudinal Studies
KW - Medical Audit
KW - Patient Selection
KW - Primary Health Care
KW - Psychological Techniques
KW - Randomized Controlled Trials as Topic
KW - Treatment Outcome
AU - S. Johansson
AU - M. A. Wallander
AU - F. J. de Abajo
AU - L. A. Garcia Rodriguez
A1 - 
AB - BACKGROUND: Post-launch drug safety monitoring is essential for the detection of adverse drug signals that may be missed during preclinical trials. Traditional methods of postmarketing surveillance such as spontaneous reporting have intrinsic limitations, many of which can be overcome by the additional application of structured pharmacoepidemiological approaches. However, further improvement in drug safety monitoring requires a shift towards more proactive pharmacoepidemiological methods that can detect adverse drug signals as they occur in the population. OBJECTIVE: To assess the feasibility of using proactive monitoring of an electronic medical record system, in combination with an independent endpoint adjudication committee, to detect adverse events among users of selected drugs. METHODS: UK General Practice Research Database (GPRD) information was used to detect acute liver disorder associated with the use of amoxicillin/clavulanic acid (hepatotoxic) or low-dose aspirin (acetylsalicylic acid [non-hepatotoxic]). Individuals newly prescribed these drugs between 1 October 2005 and 31 March 2006 were identified. Acute liver disorder cases were assessed using GPRD computer records in combination with case validation by an independent endpoint adjudication committee. Signal generation thresholds were based on the background rate of acute liver disorder in the general population. RESULTS: Over a 6-month period, 8148 patients newly prescribed amoxicillin/clavulanic acid and 5577 patients newly prescribed low-dose aspirin were identified. Within this cohort, searches identified 11 potential liver disorder cases from computerized records: six for amoxicillin/clavulanic acid and five for low-dose aspirin. The independent endpoint adjudication committee refined this to four potential acute liver disorder cases for whom paper-based information was requested for final case assessment. Final case assessments confirmed no cases of acute liver disorder. The time taken for this study was 18 months (6 months for recruitment and 12 months for data management and case validation). To reach the estimated target exposure necessary to raise or rule out a signal of concern to public health, we determined that a recruitment period 2-3 times longer than that used in this study would be required. Based on the real market uptake of six commonly used medicinal products launched between 2001 and 2006 in the UK (budesonide/eformoterol [fixed-dose combination], duloxetine, ezetimibe, metformin/rosiglitazone [fixed-dose combination], tiotropium bromide and tadalafil) the target exposure would not have been reached until the fifth year of marketing using a single database. CONCLUSION: It is feasible to set up a system that actively monitors drug safety using a healthcare database and an independent endpoint adjudication committee. However, future successful implementation will require multiple databases to be queried so that larger study populations are included. This requires further development and harmonization of international healthcare databases.
BT - Drug safety : an international journal of medical toxicology and drug experience
C5 - HIT & Telehealth
CP - 3
CY - New Zealand
DO - https://doi.org/10.2165/11319010-000000000-00000
IS - 3
JF - Drug safety : an international journal of medical toxicology and drug experience
N2 - BACKGROUND: Post-launch drug safety monitoring is essential for the detection of adverse drug signals that may be missed during preclinical trials. Traditional methods of postmarketing surveillance such as spontaneous reporting have intrinsic limitations, many of which can be overcome by the additional application of structured pharmacoepidemiological approaches. However, further improvement in drug safety monitoring requires a shift towards more proactive pharmacoepidemiological methods that can detect adverse drug signals as they occur in the population. OBJECTIVE: To assess the feasibility of using proactive monitoring of an electronic medical record system, in combination with an independent endpoint adjudication committee, to detect adverse events among users of selected drugs. METHODS: UK General Practice Research Database (GPRD) information was used to detect acute liver disorder associated with the use of amoxicillin/clavulanic acid (hepatotoxic) or low-dose aspirin (acetylsalicylic acid [non-hepatotoxic]). Individuals newly prescribed these drugs between 1 October 2005 and 31 March 2006 were identified. Acute liver disorder cases were assessed using GPRD computer records in combination with case validation by an independent endpoint adjudication committee. Signal generation thresholds were based on the background rate of acute liver disorder in the general population. RESULTS: Over a 6-month period, 8148 patients newly prescribed amoxicillin/clavulanic acid and 5577 patients newly prescribed low-dose aspirin were identified. Within this cohort, searches identified 11 potential liver disorder cases from computerized records: six for amoxicillin/clavulanic acid and five for low-dose aspirin. The independent endpoint adjudication committee refined this to four potential acute liver disorder cases for whom paper-based information was requested for final case assessment. Final case assessments confirmed no cases of acute liver disorder. The time taken for this study was 18 months (6 months for recruitment and 12 months for data management and case validation). To reach the estimated target exposure necessary to raise or rule out a signal of concern to public health, we determined that a recruitment period 2-3 times longer than that used in this study would be required. Based on the real market uptake of six commonly used medicinal products launched between 2001 and 2006 in the UK (budesonide/eformoterol [fixed-dose combination], duloxetine, ezetimibe, metformin/rosiglitazone [fixed-dose combination], tiotropium bromide and tadalafil) the target exposure would not have been reached until the fifth year of marketing using a single database. CONCLUSION: It is feasible to set up a system that actively monitors drug safety using a healthcare database and an independent endpoint adjudication committee. However, future successful implementation will require multiple databases to be queried so that larger study populations are included. This requires further development and harmonization of international healthcare databases.
PP - New Zealand
PY - 2010
SN - 0114-5916; 0114-5916
SP - 223
EP - 232
EP - 
T1 - Prospective drug safety monitoring using the UK primary-care General Practice Research Database: theoretical framework, feasibility analysis and extrapolation to future scenarios
T2 - Drug safety : an international journal of medical toxicology and drug experience
TI - Prospective drug safety monitoring using the UK primary-care General Practice Research Database: theoretical framework, feasibility analysis and extrapolation to future scenarios
U1 - HIT & Telehealth
U3 - https://doi.org/10.2165/11319010-000000000-00000
VL - 33
VO - 0114-5916; 0114-5916
Y1 - 2010
ER -