Lessons from the Iressa case

The Supreme Court on April 12 upheld two high court rulings that said the state and the Japanese unit of British drug maker AstraZeneca PLC bore no liability for fatal side effects caused by the lung cancer drug Iressa.

Lower court rulings had ordered either both AstraZeneca K.K., the Osaka-based importer of the drug, and the state or the company to pay compensation to bereaved families of the dead patients. The trial process shows that judges at various levels of courts made different judgments. But it is important for the government, drug makers and doctors to learn lessons from the lawsuits and consider how to best protect users of newly developed drugs from their side effects.

In February 2011, the Osaka District Court ordered AstraZeneca K.K. to pay some ¥60 million in compensation to 11 family members of four dead patients. As for the responsibility of the state, the ruling said that although its guidance toward the company was not perfect, it was “not irrational,” thus deciding that the state has no responsibility for the deaths.

In March 2011, the Tokyo District Court ordered both the state and the company to pay ¥17.6 million to four bereaved families of three dead patients, holding both of them responsible for the deaths. But the Tokyo High Court in November 2011 and the Osaka High Court in May 2012 reversed the lower court rulings, by turning down the plaintiffs’ demand for damages.

Thus both high courts concluded that the government and AstraZeneca K.K. were not liable for the patients’ deaths.

Iressa raised the hopes of lung cancer patients because it directly targets cancer cells and only has to be taken once a day. AstraZeneca K.K. asked the health ministry to approve the import and sale of the drug on Jan. 25, 2002. The ministry gave the approval on July 5 that year — an unusually quick action for a country where drug approval normally takes a long time. Japan became the first country to approve the drug’s import and Iressa went on sale 11 days after the approval was given.

The drug began to be widely prescribed to lung cancer patients who cannot undergo operations and those who have suffered a relapse of lung cancer. Within three months after sales began, about 7,000 people took the drug. But about 160 of them died of interstitial pneumonia, believed to be a side effect of the drug.

The trials focused on whether the instruction attached to the drug was properly written concerning its side effects. The Tokyo District Court, for example, said that it was difficult for ordinary doctors to understand, just by reading the drug’s instructions, that the side effect can be fatal.

Interstitial pneumonia was the fourth from the top in the order of side effects in the instruction accompanying the drug through Oct. 15, 2002, when AstraZeneca K.K. issued an emergency notice. The court said that it should have been placed ahead of other side effects. It also said that AstraZeneca failed to ensure safety as required by the Produce Liability Law because it failed to provide sufficient information about interstitial pneumonia as a side effect.

Because it was later found that Iressa is effective for lung cancer patients who have a certain type of gene mutation, the instruction accompanying the drug was revised in 2011 to indicate that the use of the drug should be limited to this type of patients.

At present, 7,500 people are taking Iressa annually. In the past 11 years, nearly 900 Iressa users have died of interstitial pneumonia. The percentage of deaths is decreasing.

Now that the trials are over, it is important to look at the issue from a wider perspective. Generally speaking, a clinical trial of a newly developed drug covers a limited number of patients. There were many cases in which side effects were not immediately known. In the case of a newly developed cancer drug, the number of patients taking part in a clinical trial is further limited and the possibility is high that side effects do not immediately surface.

It is dangerous to suppose that once a drug is approved, it is completely safe. Side effects often appear after a drug is used by various types of patients. Careful preventive measures are indispensable, especially during a period immediately after the start of the sale of a new drug.

There can be several ways to increase the safety of a new drug — collecting data on all the drug users’ conditions for the time being after the start of the drug’s sale, hospitalizing all the users of a new drug for some period immediately after the drug is put on sale, allowing only doctors who are specialists in particular fields to use a new drug for diseases of the fields, etc. In the case of Iressa, none of these measures was taken.

Because Prime Minister Shinzo Abe is pushing a policy of shortening the period requited to approve a newly developed drug, it is all the more important for the government, drug makers and doctors to devise ways to protect patients from side effects.

Although the April 12 rulings were unanimous rulings by the Supreme Court’s five-member No. 3 Petit Bench, two of the five justices called on the government to consider widening relief system coverage for side-effect victims to include patients affected by side effects of cancer drugs. The government should take this call seriously.

Doctors cannot be too careful in using a newly developed drug although such a drug may be able to cure a disease that could not be cured before. They should give sufficient information about a new drug to patients. Patients, on their part, should not hesitate to ask doctors to fully inform them about a new drug they take.