E-drug: Clinical trial publication requirement abolished in Japan
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Dear E-drug readers,
Watching the discussions concerning the ICH on the involvement
of non-government/industry sector, in particular, I would like
to introduce very regrettable situation of Japan and enlightening
commentary by Dr. Hirokuni Beppu, which was published on the Lancet
on 12 June 1999 (see the bottom of this mail). This April,
Japanese Ministry of Health and Welfare (MHW) abolished the
publication requirement of registration clinical trial without
consensus of consumers.
We regard this publication requirement very significant and
Dr. Beppu concludes that Japan should have used its influence
in the ICH to make disclosure of clinically relevant data the
norm in other countries too.
I hope that international discussions could overturn the decision
of Japanese MHW.
In autumn, our journal "Rinsho Hyoka" (Clinical Evaluation) is to
publish a round table discussion on this subject in which
participated Ms. Ellen 'tHoen from HAI, Dr. Hiroshi Nakajima
(former Director-General of WHO), Dr. Hirokuni Beppu, Dr. Kiichiro
Tsutani (chair of the JANCOC), Dr. Masanao Kurihara (chief editor of
"Rinsho Hyoka"), and others strongly interested in this matter.
If you are interested in this, please contact me. We are preparing
to publish the discussion on our web-site, as well.
Chieko Kurihara
Editorial Staff of Rinsho Hyoka (Clinical Evaluation)
Tokyo, Japan
http://www.sphere.ad.jp/cont/
e-mail: cont@super.win.ne.jp
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The Lancet, Volume 353, Number 9169: 1992, 12 June 1999
Japan's loss of leadership role in access to drug data
One reason for publication bias in medical science, a huge
disadvantage in the acquisition of comprehensive, balanced
information, is the reluctance of drug companies sponsoring clinical
studies to release results unfavourable to their products. So far,
only two companies (Schering UK and GlaxoWellcome) have agreed to
contribute details of all their trials to the Cochrane Clinical Trials
Register(1).
Since 1967, Japan has had a unique New Drug Application (NDA) system
that accepted only published data in applications for drug licensing.
This regulation in effect gave free access, through published papers,
to a company's information about its drugs. Pharmaceutical companies,
however, have argued that the requirement to publish the data
contravenes the GATT/TRIPSagreement (Article 39(3)). This article
first states that if undisclosed data are submitted with an
application for approval, the government must protect the company
against unfair commercial use of the information. Pharmaceutical
companies thus claim that, without assuring firms of appropriate
protection, the government cannot compel them to publish their
research on a new drug. However, the second sentence of Article 39(3)
provides an exception to the first--ie, disclosure is the principle
where it is necessary for the protection of the public. The government
is responsible to the public, so protection of the public must come
before the companies' intellectual property. Disclosure of all data
verifying drug safety and efficacy is necessary for the health and
safety of the public. Academic transparency and integrity must be
guaranteed. Thus, a request by an editor of a drug bulletin for
details of studies, for example, ought not to be seen as unfair
commercial use and should also be viewed as protection of the public.
However, the Ministry of Health and Welfare (MHW) has given in to the
drug companies and has announced that from April, 2000, companies'
unpublished work can be submitted in applications for drug appproval.
Many medical professionals, individually or jointly, and many
patients' groups publicly objected to this change. To counter these
objections, the Ministry claims that the data will be provided in the
Summary Basis of Approval (SBA). However, the SBA does not give full
details of the clinical trials. Also, since it is not subject to
external review, its scientific reliability is questionable. In
Europe, for example, health professionals view information in the
European Public Assessment Reports, the equivalent of the SBAs, as
inadequate evidence because these reports lack some essential clinical
data(2).
This controversy in Japan brings to mind the danger of secrecy as
exemplified by the Synthroid case in the USA(3). Because the
manufacturer, Boots, obstructed the publication of a study showing
bioequivalence between Synthroid and a generic preparation or a
cheaper brand of thyroxine(4), this information was withheld from the
public for 7 years. The researchers had almost abandoned efforts at
publication, but the problem was resolved by the US Food and Drug
Administration's pressure on the company. Use of the cheaper
preparations would have saved an estimated US$356 million annually.
The language barrier has hidden the fact that for 30 years Japan led
the world in access to data from drug firms. Instead of removing a
regulation that helps in the critical evaluation and rational use of
drugs, Japan should have used its influence in the International
Conference on Harmonization to make disclosure of clinically relevant
data the norm in other countries too.
Hirokuni Beppu
The Informed Prescriber, 1-43-8-404 Nishikoigakubo, Kokubunji,
Tokyo 185-0013, Japan
(1) Sykes R. Being a modern pharmaceutical company.
BMJ 1998; 317: 1172.
(2) International Society of Drug Bulletins (ISDB) Newsletter,
June, 1999.
(3) Rennie D. Thyroid storm. JAMA 1997; 277: 1238-43.
(4) Dong BJ, Hauck WW, Gambertoglio JG, et al. Bioequivalence of
generic and brand-name levothyroxine products in the treatment of
hypothyroidism. JAMA 1997; 277: 1205-13.
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