The Selling Sickness Conference, Amsterdam, 7-8 October 2010

Distorted Drug Evaluation:
IRESSA and Conflicts of Interest among Experts in Japan
Yukari YAJU 1), Masumi MINAGUCHI 1), Hirokuni BEPPU 1)
1) Medwatcher Japan, Japan

Backgrounds(1) Repeated drug-induced disasters in Japan
Drugs

Year

(2) Medwatcher Japan

1962

Thalidomide

1970

Clioquinol（Chinoform）

1970

Coralgil

SMON: subacute myelo-opticoneuropathy
Liver disease

1974

Chloroquine

Retinopathy

1984～92

1993

HIV tainted unheated coagulation AIDS
factor preparations
HCV tainted fibrinogen
Hepatitis Cpreparations
Sorivudine and 5-FUAugmentation of activity of 5-FU

2002～10

Gefitinib（IRESSA）

1987～94

・A non-profit organization including 17 members: 7 pharmacists, 5 attorneys,
1 physician, 1 consumer advocates, 1 thalidomide victim, 1 sociology professor
and 1 medical journalism professor
・Launched in 1997, the year after the legal settlement for the tainted blood
products-induced HIV litigation
・Objectives: to monitor and prevent drug-induced disasters
・Activities- To submit appeals, public questions and comments to governmental agencies
and pharmaceutical companies regarding issues related to individual drugs- Law suits based on the freedom-of-information act- Nation wide surveys- Symposia- Lobbying activities
・Cooperating with “The Informed Prescriber” (TIP) and “Non ProfitOrganization Japan Institute of Pharmacovigilance” (NPOJIP)

Adverse reactions
Phocomelia

Interstitial Lung Disease (ILD)* No. of deaths before approval: 34

・IRESSA victims(3) Drug-induced accidents due to IRESSA
・IRESSA- An orally administered drug, gefitinib for non-small cell lung cancer- An epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor- Globally first launched by AstraZeneca in Japan

Date
No. of deaths from ILD (After approved Jul. 5, 2002; accumulated *)Jul. 15, 2002
1(First report of fatality)
Dec. 31, 2002
180
Dec. 31, 2004
557
Dec. 31, 2009
799
Mar. 31, 2010
810

Objectives

Findings• To describe the conflicts of interest involving
experts, promotional advertising bypharmaceutical companies and IRESSA
drug information, and examine solutions tothose issues.

(1) Promotional advertisement masquerading as science: IRESSA’s caseCharacteristics of Contents
Methods of advertising
・Emphasis on efficacy
・Directed at all parties (doctors, patients, mass media)
・Emphasize that there are few adverse reactions ・Advertisement masquerading as providing of scientific information
・No mention of interstitial pneumonia
・Predating approval

・Promotional advertisement for medical exparts: An example of IRESSA

Methods• We reviewed the facts regarding conflicts ofinterest involving experts clarified throughthe IRESSA litigation and a promotional
advertising disguising itself as ‘scientificdrug information’. We also examined thecharacteristics of IRESSA drug information
provided by the pharmaceutical company.

･Advertisement implying that thedrug has a drastic effect and noserious adverse effects: someexamples of phrases in IRESSA
drug information

Lung cancer and Evidence-based medicine:
tailored treatment for lung cancer“The best promising
molecular targeted drug forsolid carcinoma”

ZD1839 is a drug thatshows little toxicity…
ZD1839: trial code of IRESSA(2) Inadequate warning statements“An epoch-making drug in thetreatment of lung cancer”

Presented by AstraZeneca“A wonder and dreamlike
medicine”

IRESSA package insert
1st version

・・・・・・・・

Current version(3) Conflicts of interest among 10 expart members of the IRESSA guidelines committee
No.
Name
1 N. Saijo
2 M. Fukuoka
3 S. Negoro
4 S. Kudo
5 T. Tamura
6 H. Tada

No warnings mentionedthat interstitial pneumonia
can be fatal.
Current statementsin the warnings
columnDefense witness

Member of WJOG**

Investigator of Clinical Trials of IRESSA

7 T. Mitsudomi
8 H. Kato
9 N. Yamamoto
10 K. Hayakawa** West Japan Oncology group (Twenty million yen per year was donated to the WJOG from AstraZeneca. The total amount of the donation reaches about 100 million yen.

Discussions

Conclusions(1) Promotional advertising and DTCA
・Ambiguous legal definition of advertisement for・Promote the distribution of authorised appropriate drug information to protect the public from misleading information
pharmaceuticals
provided as DTCA.
・Lack of authorised appropriate medical information for patients.
・Review the definition of the advertisement to regulate advertisement masquerading as the scientific information.
・A hotbed of drug-induced disasters
・Research the potential impact of the marketing strategy upon the activities of self-help patient group, and reveal the-Insufficient transparency of MHLW advisory committee
problems relating to the economic ties between patient support organization and drug companies.
and guidelines committee, etc.
(2) Inadequate warning statements-“Corrupted relationship” between pharmaceutical industries
・Set up the committee including patient representatives to check the contents of package inserts. The committee should
and the government.
be held ahead of the approval of drugs, being opened to the public.
-Economic ties between leading medical experts or patient(3) Conflicts of interest among experts
support organization and drug companies
・Promote the education of the medical students about issues concerning the relationship between physicians andcommercial enterprises.