It’s hard to believe I’m still alive,” says Koei Nishino, a 74-year-old retired farmer from a little village called Chosei, some 80 kilometres from Tokyo. Five years ago, Mr Nishino had an operation for cancer of the spleen and stomach, but it wasn’t the cancer that almost killed him, it was the drug he was given to counter an outbreak of herpes.
The virus attacked him last September, his immune system weakened by the anti-cancer drugs he had been taking. So his hospital doctor prescribed a new and (so the salesman had told him) highly effective drug called Sorivudine.
The pain of the herpes soon faded, but within days Mr Nishino noticed weird changes in his body, then he collapsed and had to be rushed to an emergency hospital ward where he lay in a coma for three weeks, with his family at the bedside preparing for his death.
Nearly a year later, Mr Nishino still suffers the after-effects of his close encounter – keloids (painful scarring of his face and body), swollen legs that make it difficult to walk, trouble urinating. “It is the drug company that has done this to me,” he says. “How can anyone ever feel safe again?” Mr Nishino, in fact, was one of the lucky ones. Within a month of its release, the new “wonder drug” had killed 15 people and injured scores more -many survivors, like Mr Nishino, will have long-lasting after-effects.
The almost-daily revelations in the Japanese media over the past two months about faked research, inadequate government controls, the lies, bribery and blatant profiteering that surrounded the release of Sorivudine are a medical horror story in instalments that has outraged the country.
But first, you have to understand why the Japanese are more vulnerable than Australians, say, to a rogue drug like this slipping through the regulatory safety net and on to the general market.
Japanese are the world-champion pill-poppers. They spend $80 billion a year on pills, potions and injections – more than the country’s defence budget, and almost double what they spend on the staple food, rice. They swallow twice as much medicine as Americans and three times as much as the British.
There is a phrase for this, kusuri zuke shaki, which means “drug-pickled society”. It is almost impossible to walk out of a doctor’s surgery without your pockets clattering like a baby’s rattle. It is far from uncommon for older patients to be taking six or eight different medications.
At last count, some 1,237 books were available to try to help Japanese consumers understand what is being done to their bodies. The national best-seller for the past eight years is the annually updated How to Understand the Drugs Which Doctors Prescribe, which has sold an amazing 1.8 million copies.
Doctors are not much help – informed consent is a controversial and little-understood Western concept, and thousands of patients are still used as unsuspecting guinea pigs in experiments for which hospitals are paid up to$2,600 a head by the drug companies.
There are a variety of reasons for this infatuation with drugs. One is cultural. Since the Nara period, beginning in the 8th century, kanpo, or herbal medicine, has been the traditional remedy for any ailment.
As well, there is an almost God-like trust in doctors. They cruise around in their Rolls-Royces and hold court in their surgeries, sometimes with an audience of patients watching as they diagnose and prescribe, and they are deferred to with the honorific sensei or “master”. Most Japanese GPs refuse to tell their patients what they are prescribing or even what they think is wrong with them, particularly if it is a taboo condition such as cancer or AIDS.
You are unlikely to get even this cursory attention unless you present them with a shugi bukuro, an under-the-table envelope full of cash. In fact, money is the main motive nowadays for the drug-pickled society – the Japanese national health scheme, introduced in 1962, has the Government paying doctors, clinics and hospitals for the drugs which they hand out to their patients. The more you prescribe, the more you earn.
As Japanese national health doctors are paid a pittance – my doctor says he would need to see 150 patients a day to make a living – they rely on kick-backs from the drug companies, secret discounts on the approved prices. As much as one quarter of that $80 billion-a-year is pocketed by the profession.
For the past decade or so the Government has been trying to put a lid on the soar-away cost by progressively cutting the reimbursement price on established drugs. This has led, says Dr Hirokuni Beppu, to a proliferation of”new” drugs unparalleled anywhere in the world, and despite established drug prices being cut by half from 1980-90, total sales increased 5 per cent.
Dr Beppu is the deputy medical superintendent of the Tokyo Metropolitan Hospital and editor of The Informed Prescriber, a monthly magazine which, among other things, blows the whistle on dangerous drugs such as Sorivudine.
According to him, Japan now has no fewer than 14,000 drugs listed for medical benefits compared with 600 in Australia. “There is a proliferation of’me too’ drugs, old formulae repackaged in new boxes, and new drugs, many of which are clinically worthless, and some of which, like Sorivudine, turn out to be highly dangerous,” he says.
Dr Beppu blames poor medical education – only six of Japan’s 80 medical schools have a course in clinical pharmacology – and inadequate Government supervision for the country’s proliferation of dodgy drugs. “We are notorious for this … we are far behind the US in evaluating and monitoring drugs.”
In the past 40 years, Dr Beppu’s group has listed 11 major drug disasters in Japan, which have affected up to 20,000 people and caused several hundred deaths. Some are imported, such as Enterovioform (an anti-diarrhoea drug which killed scores of people and might have blinded 3,000), and Thalidomide, which caused hundreds of shocking birth deformities.
Western drugs often do not appear on the market until long after they have been discredited in other countries.
Steroids are still referred to by doctors who should know better as “magic medicine” and prescribed for skin ailments; Interferon, a best-seller for hepatitis treatment, has recently been linked to chronic depression, resulting in 32 suicide attempts (12 successful) and two murders. Other drugs like Sorivudine are home-grown Japanese products.
Deaths have resulted from bizarre fads: the injection of vitamin K; useless”tonics” claimed to help Alzheimer’s disease patients; and the massive over-prescription of antibiotics, which led to an epidemic of the lethal MSRA bacteria in the late 1980s.
Many Westerners in Japan take their children to Hong Kong or the US for their inoculations, because defective Japanese vaccine has killed a number of children.
Most of these “only-in-Japan” drugs would never get approval in any other country, says Dr Beppu. Of all the hundreds of highly profitable anti-cancer drugs used in Japan, for instance, only two have been approved in the US. On the other hand, the low-dose contraceptive pill is still banned in Japan, to protect the lucrative abortion industry.
Japanese drug companies are, as a consequence, global minnows, almost unknown outside their own captive market. While Toyota, Sony and Fuji have become internationally admired brand-names, who has heard of Japan’s largest drug companies – Takeda, Sankyo, Shionogi – or of Nippon Shoji Kaisha, the company responsible for the Sorivudine outrage?
Nippon Shoji, originally a trading company, began planning in the mid-1980s for a “smash-hit” drug which would boost its shares when it went public in 1991. That drug, it now emerges, was an anti-viral agent which had already been tested and rejected as too dangerous in Europe, because when used in combination with certain anti-cancer drugs it killed most patients.
During their own trials, Nippon Shoji’s doctors discovered the same thing: three patients died within days of being given Sorivudine. Two of these deaths were kept secret, and a former executive of the company has explained why, with chilling candour: “It is normal (in the pharmaceutical industry) to close your eyes to bad data … it would be a big problem if a drug which cost billions of yen to develop was not approved.”
One of the deaths, however, as well as an animal trial, in which every rat died, was reported to the Health and Welfare Ministry’s Medical Deliberation Committee, the Japanese equivalent of America’s Food and Drug Administration(FDA), which is responsible for ensuring that any new drugs are both safe and effective. So, why didn’t the Government act? Nature, the prestigious British science magazine, points out in its latest issue that Japan’s drug-approval bureaucracy is woefully understaffed. It has just two inspectors to verify the integrity of clinical trials, compared with 100 in the US.
As well, bribery and collusion are rampant between the industry and the people who are its watchdogs.
A former manager at Nippon Shoji has described how the company wined and dined health and welfare bureaucrats to get Sorivudine approved. The monthly budget for entertainment was $13,000 a head. As well, if they do the right thing, the bureaucrats can expect to be offered highly lucrative seats on drug company boards when they take early retirement in their 50s.
On September 3 last year, Sorivudine was released in a blaze of hype, with Nippon Shoji’s president, Takakazu Hattori, crowing in private that it was”the most expensive drug in the world”; each pill cost $29.54, and the prescription was three a day. Within 10 days the company racked up sales of$13 million, and its shares went through the roof.
Yes, there was a tiny warning on the box – merely that it was “inadvisable”to take Sorivudine in conjunction with anti-cancer medication. Most doctors did not notice it. Certainly, no patient was ever warned there might be lethal side-effects.
On September 19, just a fortnight after the launch, the first death was reported to the company and the ministry. By September 27, the toll was eight. Still there was no public warning. Minutes of a meeting at company headquarters in Osaka show the deaths were to be a “secret within the company”. Nippon Shoji and the health ministry knew the drug was deadly, but before the public was warned there was one vital task to accomplish first: to make sure that, even if more patients lost their lives, no-one at the company lost any money.
Between September 27, when the whistle should have been blown loud and long, and October 12, when the health ministry issued a belated warning, 175 employees of Nippon Shoji dumped their shares on the Osaka stock exchange. They saved millions; after the announcement, Nippon Shoji shares plummeted from $47 to $22, where they languish today.
During that 15-day period, eight more people died. Masanori Fukushima, of the Aichi Cancer Centre, describes it as “the most shameful episode in Japanese medical history”. Various prosecutions are afoot – principally for insider trading – and the chairman and president of Nippon Shoji have both resigned. Some patients are suing. There has been vague talk of “improving the system” and adopting international protocols for evaluating and monitoring drugs.
But Koei Nishino and the other victims of Sorivudine – those who survived -have little faith that anything is about to change in Japan’s drug-pickled society.
“This is not about money; it’s about life – my life,” he says. “I haven’t seen any sign of sincerity from the drug company or the Government that they are going to change things.”
Pub: Sydney Morning Herald
Pub date: Saturday 30 July 1994
Sub section: Page: 7
Word count: 2069
Keywords: Drugs Drug abuse
Drawing: By Amanda Upton
Portrait: Koei Nishino
Photography: Mayu Kanamori