1.
Introduction
Health Action International (HAI)-Europe and the Dag Hammarskjoeld
Foundation jointly convened an International Working Group to seek ways
of promoting openness and accountability in drug regulation, both in
industrialised and developing countries. The Working Group met in Uppsala,
Sweden from 11-14 September 1996.
In recent decades, most countries of the world have established agencies
to ensure the efficacy, safety and quality of pharmaceuticals, the validity
of information relating to them, and to monitor patterns of utilisation
and matters relating to rational use. These agencies must be regarded
as servants of the public, acting to protect and advance health where
drugs are concerned.
The regulatory agencies have assumed major responsibilities and large
amounts of drug information are entrusted to them; the agencies themselves
also generate policies, procedures and decisions. The scientific community
and the public need this material but much of it is not available to
them. It is needed both to ensure the effective and safe use of drugs,
and to guarantee accountability, i.e. to provide a sound basis for scrutinising
the activities of these agencies so as to ensure that they are acting
efficiently and honestly in the public interest.
In recent years, freedom of information has become an increasingly accepted
principle in democratic societies; many national governments subscribe
to it, as do the European Commission and the World Health Organization.
The principle of openness applies to pharmaceuticals as it does in other
matters - often even more so because of the direct importance of drugs
to people's health.ù
For these reasons, the Working Group set out to consider how essential
information could be mobilised from drug regulatory agencies and their
associated bodies without injuring any valid interest.
2. The origins of confidentiality
in drug regulation
Most regulatory agencies and similar bodies have been
established by law, and specific clauses in these laws usually require
that they handle certain data confidentially. In addition, the employees
of agencies are commonly bound by oaths binding upon civil servants
requiring them to maintain secrecy on matters entrusted to them.
Two main arguments originally underlay the principle of regulatory secrecy
in the drug field:
First, it was considered that a commercial company which had used creativity
and funding to devise and develop a drug could only reap a proper reward
and fund future research by protecting it from immediate imitation by
others. While patent law would protect certain matters, others could
be protected only by maintaining secrecy.
Second, it was realized that information relating to individual persons
(for example those participating in a drug research project or those
in whom adverse reactions had been reported by physicians) would have
to be dealt with having full regard for personal integrity. These principles
need not be questioned but they need to be more fully defined. On which
matters does the need for secrecy really outweigh the general need for
openness? Where is the dividing line between legitimate trade secrets
and "commercially sensitive" data? How do secrecy clauses
in the law need to be changed?
3. Development of excessive secrecy
Drug agencies and inspectorates often maintain secrecy
to a much greater extent than law or logic actually demand. Some laws,
for example, only strictly require secrecy as regards personal data
and the method of preparation of a drug, yet one often sees that no
part of a regulatory file is accessible, and that reports about adverse
reactions or poor manufacturing standards are sealed. Various reasons
underlie excessive secrecy:
lack of legal obligation: in some countries, the law establishing
regulatory bodies does not impose on them any duty of providing information.
lack of clarity in the law: agencies or their staff may consider
it safer to apply confidential clauses broadly rather than narrowly.
lack of tradition: many countries have no tradition of transparency
in government.
lack of consistent policy: particularly in some developing countries
there are (very) frequent changes in regulatory staff and general policy
matters such as the provision of information receive little attention.
absence of explicit routines: within the agency, who is competent
to release a particular type of information, to whom, and in what circumstances?
lack of capacity and resources: particularly in underresourced
regulatory agencies, the time required to process requests for information
may in itself be a barrier.
paternalism: the frequent belief that those outside of the agency
do not need, could not cope with or would misinterpret the information.
embarrassment: an agency may hesitate to make fully public those
decisions which are poorly documented or internally contested, papers
which reflect poorly upon the agency's performance, or matters on which
it might be criticised for not yet having taken a decision.
industrial influence: many companies clearly prefer that entire
regulatory files be regarded as secret.
over-caution: there may be an exaggerated fear of upsetting commercial
susceptibilities.
bureaucratic habit and inertia: in agencies which are not subject
to critical and transparent review, habits can form which discourage
exchange of information.
4. The benefits of openness of
drug information
Full availability of information is essential if all parties
involved in health care are to participate effectively.
Openness facilitates adequate feedback, proper setting of priorities
and development of trust. A culture of openness protects conscientious
individuals working in organisations of all kinds. Knowledge relating
to all drugs evolves constantly, as do standards and expectations relating
to them, their producers and health care providers. However thorough
the investigations made before a drug is licensed and marketed, much
more will be learned about its efficacy, proper use and risks once it
is marketed and used on a much larger scale. Almost no new element of
knowledge emerges suddenly; as a rule it begins with impressions, suspicions
and hypotheses. Where these arise - for example in reports of possible
serious side effects in the journals - all existing relevant information
will need to be mobilised to verify or discount this evidence so that
the truth can be established as quickly as possible. Much of the information
needed for that purpose, including data on both animal and human experience,
is unpublished and lies only within the files of agencies. By using
it, the truth can be established much more quickly than if one is reliant
purely on published evidence.
5. Consequences of excessive secrecy
in drug regulation
Where secrecy is excessive the benefits set out in Section
4 will be lost. The risks that arise include the following: if a substantial
part of the information existing on drugs remains hidden within regulatory
agencies, and sometimes fragmented between them, the development of
knowledge will be impeded. This is particularly dangerous where suspicion
arises of a hitherto unknown risk. malpractice can be hidden from view;
legal discovery in the course of litigation has for example revealed
cases of falsification or suppression of unfavourable data by certain
companies, or submission of inconsistent files on the same drug to different
agencies. secrecy facilitates the circulation and use of sub-standard
drugs. where a drug is subject to negative findings, the failure of
a drug agency to explain its conclusions or provide background data,
can leave the way clear for the sometimes very different and emphatic
account given from the manufacturer.
in a climate of secrecy and mistrust, the public is unlikely to believe
even accurate and meticulously prepared official statements--assuming
that they cannot be taken at face value and that some relevant information
has probably been withheld. the incomplete availability and irregular
release of information promotes a climate in which suspicion is generated
and in which sensational and poorly founded stories on drugs break in
the popular press; their reliability cannot be checked and unnecessary
panic can be caused.
secrecy has consequences which can be wasteful and even inhumane; scientific
work, e.g. in humans or animals, which has already been performed by
one company but hidden within regulatory files, may be repeated unnecessarily.
if drug utilisation data are not available irrational drug use may continue
unrecognised and unchecked.
if research is sponsored by companies, unfavourable or unclear results
may be withheld or the research it self may be stopped.
6. Current trends
The Working Group noted several current trends which can
affect the free availability of drug information, favourably or otherwise.
First, the move towards adoption of Freedom of Information legislation
continues, though only a few countries have as yet taken this step and
existing laws contain important exceptions. The current trend towards
semi-privatised, industry-financed rather than tax-financed drug regulation
can increase the degree of industrial influence on the regulatory process.
The industrial preference for a high degree of confidentiality is likely
to be pressed strongly. Consolidation of drug regulatory activities
into regional and multinational agencies is increasing, and collaboration
between certain agencies is growing. This does not in principle lessen
the challenge of ensuring sufficient open ness; large regional groupings
can practice excessive secrecy as much as
national bodies.
7. General principle: Freedom
of Drug Information
In principle information available within regulatory agencies
should befreely available to any party requesting it.
This basic principle applies at least as strongly here as in other fields
of governmental activity, and exceptions to it must be defined restrictively.
There must also be a right of appeal to an independent higher authority
if the regulatory authorities initially refuse to disclose. The Working
Group further noted that:
- Availability of information must extend not only to data reaching
the agency from the outside, but also to its own deliberations, conclusions
and actions.
- Data should where possible be released with some indications as to
what is fact and what is hypothesis, but the release of the basic facts
must not be restricted or delayed in order to add such commentary.
- The provision of information should not only be passive; agencies
should actively provide and publish information in the public interest
wherever possible.
8. Valid exceptions to the principle
of free drug information
The two most important exceptions that can reasonably
be made to the principle that drug information must be freely accessible
are as follows:
a. Protection of legitimate business interests
The protection of innovative products and processes is primarily the
concern of patent law and not of drug law. However on certain issues
patent protection cannot be obtained yet there may still be a valid
interest in maintaining secrecy to protect an innovation (e.g. relating
to a manufacturing or finishing process) from competition. A feasible
approach would be for a manufacturer, when submitting a file to an agency,
to state, with reasons, which specific parts of the file are considered
confidential and for what period. This specification would be made on
a standard form allowing the authority to confer in confidence about
the types of matters accepted as justified under this exception.
b. Protection of confidential personal information
Personal data which enter the files of regulatory agencies or adverse
drug reaction agencies can include the identity of the individual patient
or health professional (or sufficient information to enable him or her
to be identified indirectly) as well as information on the illness from
which the patient is suffering and the drug treatment received. Information
which might lead to the identification of individual patients should
not be released by an agency to any party. A feasible approach would
be to ensure that all personal data entering an agency is coded in advance
in such a way that the individual cannot be individually identified,
even by the agency itself. Other limited exceptions to the principle
of openness can arise.
9. The need for transparency at
the international level
There is an increasing trend to exchange data and views
between national regulatory and adverse reaction monitoring agencies.
One example is the International Conference on Harmonisation (ICH) which
aims to harmonise regulatory requirements between the United States,
Japan and the European Union. In time, this will also have a major impact
on data handling by agencies in other regions. To date, ICH has concentrated
primarily on accelerating the process of new drug approvals; it has
scarcely considered the problems of the developing world, monitoring
of existing drugs, and the broader aspects of drug safety. Information
on ICH activities has been presented in such a way that their full repercussions
have not been widely recognised. There is little possibility for developing
countries with their special needs to influence the ICH process, and
a broader process of consultation and full accountability is lacking.
Mechanisms to ensure transparency and access to information should be
integrated into harmonised procedures.
The Working Group noted that, although the WHO International Centre
for Adverse Reaction Monitoring has been able to provide an increasing
degree of public access to the data which it holds, some of the countries
contributing data object to the release of their own information through
the Centre, even when aggregated with data received from other centres.
It was considered that these countries should be urged to allow the
public use of their data through the Centre so as to enhance the usefulness
of this international database in generating and examining early signals
of possible side effects. Conversely, agencies should be encouraged
to make fuller use at the national level of the signals now provided
by the Centre on matters of potential concern.
An important form of international exchange is that of certificates
of good manufacturing practice issued by drug exporting countries under
the WHO Certification Scheme by federal, national or provincial authorities.
Unfortunately, the reliability of these certificates varied very greatly.
The Scheme will not be of optimal value to importing countries until
there is some means of checking that a certificate has indeed been issued
on the basis of competent and independent inspection.
10. Continuing Commitment
Secrecy in medicine is a serious obstacle to the attainment
of health, in the drug field as in others. The participants in this
Working Group made a continuing commitment to promote the further development
of openness in drug regulation. They will do this by continuing to publicise
the issue, stimulating discussions on the problems surrounding secrecy
in drug regulation, surveying current disclosure policies of regulatory
agencies and promoting the development and implementation of freedom
of information laws applicable to drug regulation. The International
Working Group invites other committed groups and individuals working
towards greater access to drug information such as drug regulators,
consumer organisations, interested NGOs, the World Health Organization,
health professionals and public health associations to join its effort
and work together in an expanding network.
Uppsala, Sweden, 11-14 September 1996
APPENDIX
Some examples of the types of information to which
access is needed
As noted in Section 7, availability of information must
extend not only to data reaching the agency from the outside, but also
to its own deliberations, conclusions and actions. Some examples of
the type of documents and data which can be of particular value and
can be made available without undue effort are given below. The list
is not exhaustive and the general principle of full availability of
all data continues to apply.
- Public assessment reports providing the essential reasons underlying
the licensing of a drug and any conditions attached to the licence,
or relating to the modification of an existing licence. Where an agency
has not compiled reports for these specific purposes, its own internal
assessment reports must be made available.
- Copies of the pharmacological, toxicological and clinical reports
submitted to obtain the initial or modified registration of a drug and
those added to the file subsequently.
- Items (a) and (b) above should be accessible from the date of marketing
anywhere in the world, onwards, (as should the texts of the approved
data sheet and package insert).
- Inspection reports of pharmaceutical plants, subject only to the deletion
of personal details and material details relating to industrial secrets
and individual privacy (as defined earlier).
- Adverse drug reaction reports received from health workers, manufacturers
or other agencies, subject only to the deletion of personal data.
- Collected pharmacoepidemiology data including data on drug sales and
drug consumption.
- The internal evaluation of the relevant regulatory authority regarding
current adverse reaction reports.
- Where essential drug lists exist: publication of motivated decisions
to include particular drugs on the list or to amend the list.
- Reports relevant to the suspension, restriction or withdrawal of drug
product licences or of manufacturing licences.
- Reports on agency meetings, including meetings of scientific committees,
and hearings subject to the deletion of personal data.
Participants in the International Working Group
- Jose Ruben de Alcantara Bonfim Brazilian Society for
Drug Monitoring (Sobravime) Brazil
- Shabir Banoo Department of Pharmacy/University of Witwatersrand South
Africa
- Danielle Bardelay La revue Prescrire France
- Hirokuni Beppu The Informed Prescriber Japan
- Graham Dukes International Journal of Risk and Safety in Medicine
Norway
- Andrew Herxheimer International Society of Drug Bulletins United Kingdom
- Catherine Hodgkin Health Action International-Europe The Netherlands
- Ellen t' Hoen Health Action International-Europe The Netherlands
- Charles Medawar Social Audit Ltd. United Kingdom
- Olle Nordberg Dag Hammarskjoeld Foundation Sweden
- Eeva Ollila National Research and Development Centre for Health and
Welfare/Health Research Unit Finland
- Dzulkifli A. Razak National Poison Centre Universiti Sains Malaysia
Malaysia
- Goran Tomson Department of Public Health Sciences Division of International
Health Care Research (IHCAR) Karolinska Institute Sweden
- Bozidar Vrhovac Pharmaca Drug Bulletin Croatia
- Krisantha Weerasuriya Department of Pharmacology/University of Colombo
Sri Lanka
