Introduction
Principles and practice of drug safety assessment
Research and Services
Data resources
Patient-level validation of electronic medical information
Contact
Selected publications
Introduction
Recent safety-related withdrawals of “blockbuster drugs” such as Vioxx® (rofecoxib) and Lipobay® (cerivastatin) have, amongst other factors, led to an increased awareness of adverse drug effects and fostered drug safety research as well as new proactive regulatory approaches. At the same time, electronic documentation of patient data and electronic drug prescription (also called computerized physician order entry; CPOE) provide the basis for the generation of large automated databases containing longitudinal patient data that can today be used for pharmacoepidemiological drug safety studies. Furthermore, CPOE also opens new opportunities for electronic clinical decision support systems (CDSS) that can automatically check for contraindications, interactions and appropriate dosing at the time of electronic drug prescription, which calls for a continuous development and systematic evaluation of CDSS in clinical practice.
The Section of Pharmacoepidemiology and Drug Safety conducts pharnaco-epidemiological research and evaluates drug safety in clinical practice. It is naturally integrated into the many other activities that relate to drug safety at the University Hospital’s Division of Clinical Pharmacology and Toxicology. These include the regional pharmacovigilance center, drug information services, clinical “safety ward rounds” at the University Hospital, education and training of medical students and practicing physicians, basic research with a focus on drug transporters and pharmacogenetics, prospective clinical research, and medical informatics with own developments of CPOE and CDSS solutions.
The pharmacoepidemiology section maintains a close collaboration with The Degge Group in Arlington, VA, USA, located in the Washington D.C. area only a few miles away from the US FDA and the NIH. Other collaborations include the Department of Epidemiology at the Boston University School of Public Health, Boston, MA, USA, as well as many national and international contacts with industry, academia and regulatory authorities.
Principles and practice of drug safety assessment
„The granting of a market authorization does not mean that there are no safety issues with a product. It means that, on present evidence, those that have been identified are considered to be outweighed by the benefits.“
Amazingly concise and precise, this quote from Dr. P. Waller at the British Medicines Regulatory Agency depicts in a nutshell the challenges that we face in the field of drug safety, as well as the discrepancies in expectations that may exist between the individual patient taking a drug and manufacturers and regulators that want to offer this patient access to an efficacious yet safe pharmacotherapy.
In contrast to a drug’s efficacy, which is primarily studied in randomized clinical trials, adverse drug effects are assessed using three main sources of information, that is not only randomized clinical trials, but also pharmacovigilance data (spontaneous reports of suspected adverse drug reactions) and observational pharmacoepidemiological studies.
Today, pharmacoepidemiological studies conducted in automated databases play an increasing role for drug safety evaluations in a changing regulatory environment (see e.g. Jones 2007, Schneeweiss 2005). They can study safety outcomes efficiently in very large populations under real-life conditions; and under the condition that potential confounders are carefully considered in their design and analysis they can quantify even rare adverse drug effects with reasonable precision. Pharmacoepidemiological studies can therefore overcome some important limitations of safety analyses from clinical trials and pharmacovigilance data. Consequently, they are increasingly appreciated as a valuable source of information and as a basis for decision taking in drug safety. Furthermore, today’s proactive safety approaches also include disease epidemiology studies for safety purposes in the pre-marketing phase of a new drug, e.g. for the determination of background rates for outcomes of interest.
Only an integrated look at the complex safety data from all available information sources considering the strengths and limitations of each approach allows a comprehensive evaluation of a drug’s safety profile, which is the foundation for a rational risk-benefit assessment and, if necessary, for the right actions in order to protect the public from unnecessary risks of pharmacotherapy.
Research and Services
We conduct original pharmacoepidemiological drug safety research, which may be investigator initiated or performed as a service under contract with the pharmaceutical industry or regulatory authorities. Furthermore we can also provide a range of additional related services in the area of drug safety.
Our expertise and services include:
- Formal pharmacoepidemiological studies (cohort and case-control studies) in large automated databases
- Drug utilization studies
- Disease epidemiology studies in a drug safety context
- Hospital-based safety studies and evaluation of computerized physician order entry (CPOE) with clinical decision support systems (CDSS)
- Evaluation of pooled safety data from randomized clinical trials
- Evaluation of pharmacovigilance data
- Independent comprehensive drug safety expert reports
Data resources
We have research experience with a range of large automated medical records and claims databases suitable for pharmacoepidemiological research. These include the GPRD (UK), Henry Ford Health System (USA), Pharmetrics (USA), Thomson Medstat's MarketScan and Medicare (USA), and AMSP (CH/D/A).
Patient-level validation of electronic medical information
Regardless of the data source, we consider patient-level validation of electronic medical information arranged in chronological order making the individual clinical context visible as an essential step for all formal pharmacoepidemiological safety outcomes studies. This approach is an important method for us in order to decide on the best possible study design and to achieve reliable results and interpretations. For that purpose we developed a software solution named Phynx, a flexible and highly efficient data management and validation tool for pharmacoepidemiological research studies in the UK GPRD and other databases.
Contact
PD Dr. med. Stefan Russmann
Head of Pharmacoepidemiology and Drug Safety
Clinical Pharmacologist and Toxicologist
Adjunct Associate Professor of Epidemiology, Boston University
e-mail: stefan.russmann@usz.ch
phone: +41 - 44 - 255 2067
Selected publications
e-mail for reprint requests
Egbring M, Kullak-Ublick GA, Russmann S.
Phynx - An Open Source Software Solution Supporting Data Management and Web-based Patient-Level Data Review for Drug Safety Studies in the General Practice Research Database and Other Health Care Databases.
Pharmacoepidemiology and Drug Safety 2009 Sep 23 (Epub ahead of print)
Motsko SP, Russmann S, Ming EE, Singh VP, Vendiola R, Jones JK.
Effectiveness of Rosuvastatin Compared to Other Statins for the Prevention of Cardiovascular Events - A Cohort Study in 395'039 Patients from Clinical Practice.
Pharmacoepidemiology and Drug Safety 2009 Sep 24 (Epub ahead of print)
Russmann S, Kullak-Ublick GA, Grattagliano I.
Current concepts of mechanisms in drug-induced hepatotoxicity.
Curr Med Chem 2009; 16:3041-3053.
Russmann S, Lamerato L, Motsko SP, Pezzullo J, Faber MD, Jones JK.
Risk of Impaired Renal Function After Colonoscopy: Risk of Further Decline in Renal Function After Use of Oral Sodium Phosphate or Polyethylene Glycol in Patients With a Preexisting Glomerular Filtration Rate Below 60 ml/min.
American Journal of Gastroenterology 2008 Nov, 103(11):2707-16.
Russmann S, Lamerato L, Marfatia A, Motsko SP, Pezzullo J, Olds G, Jones JK.
Risk of Impaired Renal Function After Colonoscopy: A Cohort Study in Patients Receiving Either Oral Sodium Phosphate or Polyethylene Glycol.
American Journal of Gastroenterology 2007 Dec;102(12):2655-63.
Jick H, Kaye JA, Russmann S, Jick S.
NSAIDs and acute myocardial infarction in patients with no major risk factors.
Pharmacotherapy 2006; 26(10):1379-87.
Jick SS, Kaye JA, Russmann S, Jick H.
Risk of Nonfatal Venous Thromboembolism Comparing Oral Contraceptives Containing Norgestimate or Desogestrel with Oral Contraceptives Containing Levonorgestrel.
Contraception 2006; 73(6):566-570.
Jick SS, Kaye JA, Russmann S, Jick H.
Risk of nonfatal venous thromboembolism in women using a contraceptive transdermal patch and oral contraceptives containing norgestimate and 35 microg of ethinyl estradiol.
Contraception 2006; 73(3);223-228.
Russmann S, Portincasa P, Palmieri VO, Palasciano G, Grattagliano I.
Ribavirin-induced anemia: mechanisms, risk factors and related targets for future research.
Curr Med Chem 2006; 13 (27):3351-7
Russmann S.
Case reports of suspected adverse drug reactions: case reports generate signals efficiently.
Brit Med J 2006; Feb 25; 332(7539):488
Russmann S, Kaye JA, Jick SS, Jick H.
Risk of cholestatic liver disease associated with flucloxacillin and flucloxacillin prescribing habits in the UK: cohort study using data from the UK General Practice Research Database.
Br J Clin Pharmacol 2005;60(1):76-82.
Russmann S, Lauterburg BH, Helbling A.
Kava hepatotoxicity.
Ann Intern Med 2001;135(1):68-9.