The recent implementation of the International Conference on Harmonization's E2C Guidelines was an important step toward globalizing the activities of drug safety departments. While many details have not yet been addressed, the primary objective of this initiative is clear: the preparation and worldwide submission of standardized periodic reviews of a marketed product's safety record. This article presents a strategy for integrating surveillance activities and epidemiological principles into periodic safety update reporting (PSUR), while at the same time meeting the regulatory requirements set forth in the ICH E2C Guidelines. A stepwise approach to PSUR compilation, interpretations of critical subsections of the ICH E2C Guidelines, and issues unique to the United States reporting environment are discussed.
Food and Drug Administration.International Conference On Harmonisation: Guideline On Clinical Safety Data Management: Periodic Safety Update Reports For Marketed Drugs. Availability Notice, Federal Register. [Docket No. 96D-0041]. 1997;62(96, May 19):27470–27476.
2.
GoldsmithDL. The impact of the international conference on harmonization (ICH) on pharmacoepidemiology and pharmacovigilance. Pharmacoepi Drug Safety.1998;7:289–291.
3.
VenuletJ. Possible strategies for early recognition of potential drug safety problems. Adv Drug React Ac Pois Rev.1988;1:39–42.
4.
RoyallBWVenuletJ. Methodology for international drug monitoring. Meth Inform Med.1972;2:75–86.
5.
Food and Drug Administration. FDA Web Page: AERS, 1998.
6.
SeidlLGThorntonGFSmithJWCluffLE. Studies on the epidemiology of adverse drug reactions. III. Reactions in patients on a general medical service. Johns Hopkins Med J.1966;119:299–315.
7.
KramerMS. Assessing causality of adverse drug reactions: Global introspection and its limitations. Drug Inf J.1986;20:433–437.
8.
KramerMSLeventhalJMHutchinsonTAFeinsteinAR. An Algorithm for the operational assessment of adverse drug reactions: I. Background, description, and instructions for use. JAMA.1979;242:623–632.
9.
NaranjoCABustoUSellersEMSandorPRuizIRobertsEAJanecekEDomecqCGreenblattDJ. A method for estimating the probability of adverse drug reactionsClin Pharmacol Ther.1981;30: 239–245.
10.
HutchinsonTALaneDA. Assessing methods for causality assessment of suspected adverse drug reactions. J Clin Epidemiol.1989;42:5–16.
11.
LaneDA. The logic of uncertainty: Measuring degree of belief. Drug Inf J.1986;20:445–453.
12.
LaneDAKramerMSHutchinsonTAJonesJKNaranjoC. The causality assessment of adverse drug reactions using a Bayesian approach. Pharmaceut Med.1987;2:265–283.
13.
EdwardsIRLindquistMWiholmBENapkeE. Quality criteria for early signals of possible drug reactions. The Lancet.1990;336:156–158.
14.
BlumMDGrahamDJMcCloskeyCA. Temafloxacin syndrome: Review of 95 cases. Clin Inf Dis.1994;18:946–950.
15.
The Pink Sheet.1998; June 29:13–14.
16.
VenningGR. Identification of adverse reactions to new drugs. I: What have been the important adverse reactions since thalidomide?Br Med J.1983;286: 199–202.
17.
LiDLindquistMEdwardsIR. Evaluation of early signals of drug-induced Stevens-Johnson Syndrome in the WHO ADR Database. Pharmacoepi Drug Safety.1992;1:11–18.
18.
Food and Drug Administration.International Conference On Harmonisation: Guideline On Clinical Safety Data Management: Definitions And Standards For Expedited Reporting. Availability Notice, Federal Register [Docket No. 93D-0203]. 1995;60(40, Mar1):11284–11287.
19.
Federal Register.Vol 62, Number 122, June 25, 1997;34166–34168.
20.
NapkeE. Drug adverse alerting program. Can Pharm J.1968;20:251–254.
21.
FinneyDJ. Statistical aspects of monitoring for danger in drug therapy. Meth Inform Med.1971;10:1–8.
22.
RoyallBW. International aspects of the study of adverse reactions to drugs. Biometrics.1971;27: 689–698.
23.
TsongY. False alarm rates of statistical methods used in determining increased frequency of reports on adverse drug reaction. J Biopharm Stat.1992;2: 9–30.
24.
NorwoodPKSampsonAR. A statistical methodology for postmarketing surveillance of adverse drug reaction reports. Stat Med.1988;7:1023–1030.
25.
Tubert-BitterPBegaudBMondeYChaslerieAHaramburuF. Comparing the toxicity of two drugs in the framework of spontaneous reporting: A confidence interval approach. J Clin Epidemiol.1996;49: 121–123.
26.
RossiACHsuJPFaichGA. Ulcerogenicity of Piroxicam: An analysis of spontaneously reported data. Br Med J.1987;294:147–150.
27.
TubertPBegaudBHaramburuFPereJC. Spontaneous reporting: How many cases are required to trigger a warning?Br J Clin Pharmac.1991;32: 407–408.
28.
BegaudBMorideYTubert-BitterPChaslerieAHaramburuF. False-positives in spontaneous reporting: Should we worry about them?Br J Clin Pharmac.1994;38:401–404.
29.
21 C.F.R. § Section 314.80, C2(ii) (1995).
30.
Medicines Control Agency.MCA News. Mail 101; May/June 1997;2–3.
