When a major medical study requires years of intensive patient participation, such as daily injections or weekly hospital visits, researchers head to Finland.
This chilly country of 5.3 million people is a key place for research, doctors and drug companies say, citing a national culture of reliability and meticulous records on the population's health history.
"Finnish patients don't just disappear and drop out of studies like in other countries," says Juhani Ramoe, medical director of Sanofi-Aventis SA's Finnish unit, which focuses on psychiatric, cardiovascular, and diabetes medications.
Groundbreaking Finnish studies already have helped uncover some of the causes of heart disease. Much of the current drug research in the country is focused on cancer, capitalizing on a trove of detailed case records and population data. Every Finnish cancer case since 1953 is logged in a database kept by the Cancer Society of Finland. Minute details are recorded, from the type of tumor to the course of the patient's illness, giving researchers a crucial baseline for identifying larger cancer trends or measuring the effectiveness of experimental treatments. The country has separate databases for heart disease, diabetes and a range of other illnesses.
"I call it our gold mine," says Eero Pukkala, the cancer registry's director of statistics. "We can take the exact coordinates of every landfill site, magnetic field, and polluted area and records on people's residential history and cross-reference all of this with our cancer registry."
John Boice Jr., a cancer epidemiologist at Vanderbilt University in Nashville, Tennessee, and the scientific director at the International Epidemiology Institute in Rockville, Maryland, has been conducting research in Finland for more than 20 years. In one study, he cross-referenced the country's cancer and population databases to determine whether people who use mobile phones have a higher risk of cancer; they don't, he found. Finland has "phenomenal health registries that facilitate high quality medical research," Mr. Boice says.
Finland's databases are the legacy of centuries of population registration, first used by a ruling Swedish king in the 1500s. Other Nordic countries have similar databases, but Mr. Pukkala said Finland's databases are more easily cross-referenced and were the first to go digital, starting in 1961, when 80 characters from each case were stored. By the mid-1980s, every case since 1953 was fully digitized, including doctors' handwritten notes.
"You can't have these kinds of registries in the U.S.," says Sanofi's Dr. Ramoe, who trained as a chest surgeon and spent part of his career as a researcher in Ohio and Florida. "The system is too big, and there is too much variation in the quality" of care and research methods. He says Finland is a better environment than the U.S. for clinical studies.
For this reason, pharmaceutical companies are placing large bets on Finland. Thirty-seven drug makers conduct clinical trials in the country, with 410 studies involving almost 34,000 patients under way at the end 2005, according to Pharma Industry Finland, an industry lobby group. By comparison, in the U.K. -- Europe's largest site for drug trials -- between 1,000 and 1,110 trials are approved every year, though not all are carried out, according to the Medicines and Healthcare Products Regulatory Agency in London.
Heart attacks first put Finland on the medical-research map. The country long suffered from one of the world's highest rates of cardiovascular disease. In the early 1970s, Pekka Puska led a research team that set out to understand why. Dr. Puska, who now heads Finland's National Public Health Institute, studied Northern Karelia, a region in eastern Finland where men in their 40s were dying from heart attacks. He used what was then a novel approach, looking at broader features of the community rather than just examining sick patients.
"We had a huge advantage doing the research in this area," Dr. Puska says, citing reams of health records and the population's homogenous habits that included a diet heavy in butter and sausages. Dr. Puska and his team urged people to eat less fat. They lobbied local dairy farmers to switch to crops like apples and berries and passed out leaflets in local supermarkets detailing the benefits of a healthier diet. Smoking and alcohol also were singled out as risk factors.
Because of Dr. Puska's work, overall life expectancy for Northern Karelian men is now 73 years, up from the 65 years seen when the study began. Meanwhile, mortality rates for males in their 40s have dropped by more than 80%.
Thirty years ago, Ilpo Antikainen, a financial adviser from Northern Karelia, would have been a prime candidate for a fatal heart attack. Today, the 46-year-old, a burly man with a brush of blond hair and a neatly trimmed mustache, has better prospects. "I don't eat too much grease or salt, and I try not to drink too much," he says over a single beer with colleagues in Helsinki. No one at the table is smoking. "It's because of Pekka Puska," he adds, without prompting.
This kind of dedication to healthier living shows a diligence that makes Finns ideal research subjects. Dropouts -- the patients who quit taking medicines or stop showing up for tests -- are the bane of medical research. They are expensive since they often receive special medical care or costly drug compounds without contributing to a study's final results. Dropouts can also skew crucial data, especially if they disappear without giving a reason. Dropouts are rare in Finland, according to Anita Leppamaki, who coordinates Sanofi's drug trials in the country. While she admits that middle-aged Finnish men can be a "difficult breed" who often resist going to the doctor, she says they almost always show up for tests and follow-up appointments, sometimes dragged in by their wives. "Their sense of duty prevails," she says.
National culture shouldn't be underestimated, doctors and researchers say. Finns are famous for a quality called "sisu," a term that has the sense of never giving up and was long used to describe to the country's world-class long-distance runners, according to Stephen Mitchell, who heads Harvard University's folklore and mythology department.
A heart study in the U.S. typically has a 20%-30% dropout rate, according to Eric Topol, a cardiologist at Case Western Reserve University in Cleveland. The dropout rate for similar studies in Finland is half that or less, Sanofi's Dr. Ramoe says.
"Over the past decade there has been an attrition of trust in clinical research in many countries," says Dr. Topol, who blames well-publicized disasters like a recent U.K. study where several patients almost died after taking an experimental anti-inflammatory drug. Finland has never had such a scandal, and patients remain enthusiastic test subjects, researchers say.
Admittedly, Finland is a bad choice for some next-generation pharmaceutical research, such as trials for new drugs to treat high blood pressure or diabetes. The country's health system provides high quality, free care, so patients with such problems typically are already taking proven medications, making them reluctant to try experimental drugs. For so-called naive patients who aren't receiving existing treatments, companies like Sanofi look to Eastern Europe or India, according to Dr. Ramoe.
Finns are better suited to long-term, strenuous testing. A daily insulin injection demands discipline, especially for people who don't have diabetes. That is just the sort of thing Finns are good at, making them ideal guinea pigs in a current study at the Helsinki University hospital probing the link between elevated blood-sugar levels and cardiovascular disease.
More than 200 patients are keeping their plasma blood-sugar levels in a tightly controlled range, said Mikko Syvanne, one of the lead investigators in the international study, which includes about 13,000 patients world-wide. Dr. Syvanne, a cardiologist, says Finland likely will provide key data for the study, due to finish in two or three years. He notes that an earlier blood-sugar trial in the U.K. was plagued by dropouts and turned up inconclusive results. "Finns have benefited from medical research," Dr. Syvanne says. "My patients often tell me how they feel they should give back, how they have an ethical purpose in participating."
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