The Perception and Management of Drug Safety Risks

218 Pages·1989·7.04 MB·English

by  J. Orsinger (auth.), Dr. Bruno Horisberger, Dr. Rolf Dinkel (eds.)

HEALTH SYSTEMS RESEARCH
Edited by K. Davis and W. van Eimeren
B. Horisberger R. Dinkel
(Eds.)
The Perception and
Management
of Drug Safety Risks
With 29 Figures and 13 Tables
Springer-Verlag
Berlin Heidelberg New York
London Paris Tokyo
Dr. Bruno Horisberger
Interdisciplinary Research Centre
for Public Health
Rorschacher StraBe 103c
CH- 9007 St. Gallen
Dr. Rolf Dinkel
HealthEcon Ltd.
SteinentorstraBe 19
CH-40S1 Basel
ISBN-13:978-3-642-74274-3 e-ISBN-13:978-3-642-74272-9
DOl: 10.1007/978-3-642-74272-9
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Preface
In the past two decades public debate about the risks, benefits, and safety associated
with drugs has intensified. Public disputes over risks are brought to court when
individuals seek compensation for health problems attributed to a pharmaceutical
product. The issue reaches legislatures and regulatory agencies when consumer
advocates seek to influence the standards of drug usage. Front-page news tends to
focus on accidents or other risk events with drugs.
Drug risk and drug safety have become an important political issue. Drug regulat
ory agencies have been instituted, and their responsibility has increased. The
approval to market a drug is dependent on a set of sophisticated studies executed
according to strict protocols and scientifically defined criteria. Drug surveillance
activities have gained recognition, and reporting systems to identify drug safety
problems have been strengthened. The understanding and management of drug
safety is, nonetheless, beset by doubts, disagreements, and disputes. Conflict occurs
over the significance of risk, the adequacy of evidence, the methodologies used to
evaluate and measure risk, the standards that guide regulation, and the optimal means
of communicating risk information to the public.
An international and interdisciplinary conference, convened by Ciba-Geigy in the
spring of 1988, was designed to explore these areas of conflict from every angle and to
initiate a collaborative effort to address existing shortcomings. The meeting at Wolfs
berg, a historic estate overlooking Lake Constance, was a continuation of previous
Wolfsberg Conferences dealing with issues of health care such as cost sharing,
technology assessment, and socioeconomic evaluation of drug therapy.
The 1988 conference assembled academic experts in pharmacology, epidemiology,
risk perception research, risk communication, and regulatory affairs, together with
representatives of 30 leading pharmaceutical companies from 10 countries.
The Council for International Organizations of Medical Sciences (ClaMS) was
represented as well as an industry association, the International Federation of Phar
maceutical Manufacturers Associations (IFPMA). Leaders of the consumer move
ment and representatives of the media participated actively in the debate.
This heterogeneous audience reflected the conference rationale: that the manage
ment of drug safety and risk is no longer a concern specific to the pharmaceutical
industry, but has gained a social dimension.
Speakers and discussants emphasized common concerns and showed a strong
interest in a collaborative approach to addressing them. Multidisciplinary collabora
tion was recognized as the sine qua non of successful management of drug risks.
VI Preface
In Part I of this book the drug safety issue is put in the larger perspective of the
worldwide public debate on technological risks in an increasingly industrialized
world. Many people have become sceptical and frightened of advanced technologies.
Risk acceptance, however, constitutes an inherent part of human life and is a prere
quisite for the development of human civilization and culture. To balance risks against
benefits, to define acceptable risk, and to exclude what no longer falls within this
category remain perpetual challenges.
Benefitlrisk assessment often leads to controversy because it involves both factual
analysis and value judgements. Within a given country, different groups have differ
ent stakes in defining the risks and benefits of drugs and evaluating the acceptability of
the risks and benefits. At the international level, cultural and political values and
expectations influence the way in which potential risks are perceived, evaluated, and
controlled. Several authors analyze the factors which influence public perception of
risks and benefits and propose means of anticipating, identifying, evaluating, and
managing controversy about risks to health. A concluding paper presents a brief
analysis of the significance of the major drug issues that have occurred in recent years
and demonstrates the extent to which these issues are related to either efficacy,
information, quality, cost-effectiveness, or safety. Of these five categories, safety
concerns are predominant in the assessment, appraisal, and communication of the
benefit/risk relationship of drugs.
Part II deals more specifically with benefit/risk analysis and appraisal in connection
with drugs. Several authors delineate the current status, limitations, and pitfalls of
pharmacoepidemiology resources and biostatistical data interpretation. The data
bases available today are not sufficiently comprehensive to show all possible adverse
reactions to drugs. Computer-based medical records linkage systems could help solve
this problem. A case study about public controversy and government intervention
related to adverse reaction reports on a nonsteroidal anti-inflammatory drug demon
strates the vital importance of adverse drug reaction reporting and other epidemiolog
ical resources in establishing regulatory and public consensus regarding the safety of a
drug. Two papers present results of recent surveys of physician and public perception
of hazardous activities and pharmaceuticals in Sweden and Japan. One finding is that,
by providing information to the public about the adverse reactions possibly associated
with a drug's use, the public's acceptance of drug risks may be increased. Another
interesting finding is that physicians believe that their patients require relatively little
information regarding medication, while patients indicate that they expect fairly
comprehensive information.
Regulatory decisions are affected by both scientific and social considerations.
Analysis and assessment of risk and benefit must be distinguished from the evaluation
of the data. Whereas analysis and assessment are processes in which the scientific
components prevail (e. g., animal and human data bearing on the safety of
medicines), the evaluation of the data obviously goes beyond scientific evidence.
Social and political factors (e.g., patient group interests, the media, economic
pressures, ethical concerns) playa major role, the relative importance of which varies
from country to country and over time. In regulatory decision making, scientific
evidence and individual perceptions are closely intertwined. Information is assimi
lated and interpreted in different ways by professional groups and the general public.
Preface VII
Media coverage about risk analysis and appraisal influences policy decisions and
stimulates public interests.
"Identify with the people who take the risks, then people will identifiy with you."
This statement expresses the concern of several authors in Part III. This section deals
with the consumer's perspective on pharmaceutical risk. The industry not only needs
to develop a much better understanding of consumer perceptions but must also
develop more effective ways of communicating with consumers. The industry's over
all good track record in providing "hardware" - medicines and other therapeutic aids
- has not been matched by its performance in providing "software" - information that
the nonspecialist can understand. The challenge for the pharmaceutical industry is,
therefore, to ensure that the patient is properly informed about the therapy and the
risk associated with its use. A willingness and ability to communicate are key to
improving society'S acceptance of risk.
Part IV comprises, in a standardized format, a number of specific collaborative
drug risk evaluation and management projects to the international pharmaceutical
industry. The proposals cover the themes dealt with at the conference: phar
macoepidemiology, risk perception analysis, communications regarding the benefit!
risk relationship, and risk appraisal on an international scale.
In Part V of this book the organizer of the conference expresses the conviction that
people have great expectations for action and improvement. He concludes by sum
moning the pharmaceutical industry to transcend traditional boundaries and to reach
out more imaginatively toward the industry's ultimate reason for being: the preserva
tion and improvement of human life.
Part VI contains the curricula vitae of the authors, a very extensive bibliography,
and index sections on subjects and data sources for those who want either to follow a
topic that the book itself does not use as a structural principle or to seek specific
information.
Contents
Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . V
List of Participants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. XIII
List of Companies and Institutions Represented. . . . . . . . . . . . . . . . . . .. XXI
Opening Address: J. ORSINGER. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Part 1: Society and the Benent/Risk Relationship
1. Acceptable Risk in Society
A. KRAUER ................................. . 5
2. A Broad Framework for Confronting Health Risks
W.W. LOWRANCE. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
3. Communicating the Risks and Benefits of Technology:
The Case of Pharmaceuticals
D. NELKIN ........................................ 19
4. Overview of the Drug Safety Issue and Ciba-Geigy's Response:
RAD-AR
W.P. VON WARTBURG . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 37
5. Summary of Part I: Presentations and Discussions. . . . . . . . . . . . . . .. 45
Part II: BenentlRisk Analysis and Appraisal
6. Limitations of Available Sources of Data on Prescription Drug Safety
H. A. GUESS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 51
7. Strategies, Designs, Criteria, Tactics and Statistics to be Considered
when Evaluating Scientific Evidence
W.O. SPITZER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 57
X Contents
8. Statistics in Drug Risk Research:
The Background of Pharmacoepidemiology
H. LETZEL. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 70
9. Industry-Sponsored Risk Institutes
W. W. LOWRANCE. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 77
10. The Feldene Experience: A Case Study
R.M.SACHS,G.S.DIECK . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 81
11. Risk Perception of Prescription Drugs: Report on a
Survey in Sweden
P. SLOVIC, N. N. KRAUS, H. LAPPE, H. LETZEL, and T. MALMFORS ...... , 90
12. Risk Perception of Prescription Drugs: Report on Surveys in Japan
S. FUITNO . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 112
13. Scientific and Political Components of Regulatory Decision Making:
General Considerations
G. FULGRAFF . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 117
14. Scientific and Political Components of Regulatory Decision Making:
The United States Experience
L. LASAGNA. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 121
15. Summary of Part II: Presentations and Discussions . . . . . . . . . . . . . .. 128
Part HI: Current Challenges
16. Professional Drug Information: A Consumer Perspective
C.MEDAWAR. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 135
17. Going Patient, Going Public
P.F. CARPENTER. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 141
18. Reporting Adverse Drug Reactions: The Media Approach
P.J.BROWN. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 149
19. What Can Be Learned from Drug Safety Issues?
G. LEWANDOWSKI. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 158
20. Summary of Part III: Presentations and Discussions. . . . . . . . . . . . . .. 161
Part IV: Responding to the Issues
21. Editor's Note ...................................... 167
22. Pharmacoepidemiology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 169
Comparative Data Base Analysis
NSAIDs Data Base
Management Training in Epidemiology
23. Risk Perception Analysis 172
Public Perception
Perception Research
24. Communicating the BenefitlRisk Relationship. . . . . . . . . . . . . . . . .. 174
Communication Proposals
Participating in the Public Debate: The United Kingdom as an Example
Political Intelligence System
25. Risk Appraisal on an International Scale ..................... 177
Council for International Organizations of Medical Sciences
Pharmaceutical Risk Management Activities in Japan
Establishment of Risk Institutes
Part V: Outlook
26. The Wolfsberg Questions
W. P. von WARTBURG. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 183
Part VI: Annex
27. Curriculum Vitae of Authors. . . . . . . . . . . . . . . . . . . . . . . . . . . .. 189
28. Bibliography...... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 193
29. Subjectlndex . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 203
30. A Handbook of International Data Sources for Drug
Benefit/Risk Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 207
List of Participants
Dr. RICHARD B. ARNOLD
Executive Vice-President, International Federation of Pharmaceutical
Manufacturers Associations, Geneva, Switzerland
Dr. MICHEL AURICHE
Head of Drug Safety Department, RhOne-Poulenc Sante, Antony, France
Prof. ZBIGNIEW BANKOWSKI
Executive Secretary, Council for International Organizations of Medical Sciences
(CIOMS), Geneva, Switzerland
Dr. EDWARD A. BORTNICHAK
Director, Pharmacoepidemiology, Pharmaceutical Division,
Ciba-Geigy Corporation, Summit, NJ, USA
Dr. ARNo BRANDT
Director, Institute for Medical Informatics, Basle, Switzerland
PATRICIA BROWN
European Editor, SCRIP World Pharmaceutical News, Richmond, Surrey, UK
Dr. PHILIP J. BROWN
Publisher and Managing Director, SCRIP World Pharmaceutical News,
Richmond, Surrey, UK
Prof. RUDOLF BRUPPACHER
Head of Pharmacoepidemiology and Drug Safety, Ciba-Geigy Ltd.,
Basle, Switzerland
Dr. DENNIS M. BURLEY
Director, Centre for Pharmaceutical Medicine, Woking, Surrey, UK
LESLEY BYGRAVE-MALIN
Chairman and Managing Director, Medical Viewpoint Ltd., London, UK