02.28.2016
Aggressive, ethically questionable drug marketing goes global
by Frederik Joelving
Contributing Writer, MedPage Today
When findings from a survey of thyroid disorders in India hit the news in 2013, the headlines were not subtle. “India’s cities in the grip of thyroid disease as new study reveals one in ten suffer from disorders,” blared one. “Time to get your thyroid checked,”another exhorted.
But the survey was bogus, experts now say.
Instead of straightforward population sampling, it relied on tests done at free clinics paid for by drugmaker Abbott India. Because such events attract disproportionate numbers of sick people in India, where many lack access to affordable healthcare, it was a recipe for inflated prevalences.
“They should have known how inappropriate this was,” said Gordon Guyatt, MD, MSc, BSc, Distinguished University Professor in the department of clinical epidemiology and biostatistics at McMaster University in Hamilton, Ontario.
“And if they knew how inappropriate it was, to make the claims they did is ethically at best questionable,” he told MedPage Today.
Ethics may not have been a top priority when the survey was done. Initiated and funded by Abbott India, a subsidiary of U.S.-based Abbott Laboratories, it was part of the company’s award-winning “Think Thyroid Think Life” disease-awareness campaign, which critics say is using shaky science and misleading health information to boost sales.
The campaign dates back more than a decade, but picked up steam in the late 2000s. Since then, an impressive array of Bollywood brand ambassadors, high-profile doctors, TV spots, media reports, roadshows, and web quizzes have helped create awareness of thyroid disorders in India.
Abbott India has also provided discounted blood tests at doctors’ offices across the country, organized mass screenings in cities and villages, trained thousands of doctors on how to manage the disorders, and funded specialist groups, guidelines, continuing medical education and lectures on the topic. (See accompanying article detailing the program.)
“They have made doctors think thyroid, they have made patients think thyroid,” said Shashank Joshi, MD, DM, president of The Endocrine Society of India and a paid speaker for Abbott.
Meanwhile, sales of the company’s flagship product Thyronorm, one of many branded versions of generic levothyroxine on the Indian market, increased seven-fold. It is now among the 10 top-selling drugs in India, grossing more than $41.5 million in 2015, according to provisional data from IMS Health.
Although that may seem like a small amount by American standards, it is enough to buy a year-round supply of Thyronorm for some 6 million people in India. That’s more than the total expected number of clinically hypothyroid individuals in India, if prevalence is the same as in the U.S., where it is estimated at 0.3% of the population (actual prevalence in India is unknown).
Thyronorm is one of a number of products, including sleeping pills and antidepressants, from Abbott India’s Specialty Care division, which “focuses on a science-based, patient-centric approach to shape and grow the market by driving awareness and diagnosis in key therapy areas,” according to the company’s 2014-15 annual report.
While Abbott is pitching its activities as corporate social responsibility, others see it differently.
“This blurs the line between what’s marketing and what’s a public-health message, and that’s why disease-awareness campaigns are particularly insidious and disturbing,” said Lisa Schwartz, MD, MS, who co-directs the Medicine in the Media Program at The Dartmouth Institute for Health Policy and Clinical Practice in Lebanon, N.H.
Everyone agrees overt, symptomatic hypothyroidism should be treated. But there is no good evidence to support treating the much more common subclinical hypothyroidism, in which only thyroid stimulating hormone (TSH) is abnormal. What’s more, screening for thyroid dysfunction has not been evaluated in randomized trials, and guidelines disagree on the question. The U.S. Preventive Services Task Force last year found insufficient evidence to make a recommendation.
That opens the door to medicating a lot of people who will not get any benefit from levothyroxine, yet will still be exposed to the side effects, argue Schwartz and her husband, Steven Woloshin, MD, MS, the other co-director of the Medicine in the Media Program.
They are expert witnesses in a lawsuit against testosterone producers, which claims, among other things, that aggressive marketing has caused rampant unwarranted and dangerous testosterone use in the U.S. through promotion of “low-T” as a condition to be treated.
“You could substitute the word ‘low-T’ for ‘thyroid,'” Woloshin told MedPage Today. “It’s exactly the same as the ‘low-T’ campaign.”
A booklet that Abbott India has distributed to doctors’ offices across India includes a flow diagram called “Laboratory test for diagnosis of thyroid disorders.” It defines a TSH level above 4.5 mIU/L as “high”, with an arrow leading straight to hypothyroidism. Then follow two pages about the dangers of forgoing treatment — depression, heart problems, edema, decreased fertility — with no mention of the uncertain balance between harms and benefits when treating subclinical disease.
“They did not say anything about the thyroid-hormone levels in the blood, so clearly they are mislabeling hypothyroidism as one group,” said Juan Brito, MD, MS, an endocrinologist at the Mayo Clinic in Rochester, Minn.
He worries the booklet, though intended for patients, could lead primary care doctors in resource-poor areas to prescribe treatment based solely on a mildly elevated TSH, which research shows often normalizes on its own.
“And patients will agree because any abnormality in the lab, in the blood, we think of as a disease instead of just normal variation,” Brito told MedPage Today. “They are misinforming everybody here.”
An Abbott spokesperson said in an email that the firm “does not recommend treatments to patients — this is at the discretion of the physician.” He added that “Abbott supports disease awareness education programs for health conditions where there is an unmet need and where awareness about the disease condition is low.”
The Endocrine Society of India’s Joshi deflected concerns about excessive treatment. “I always look at the positive side of life, not at the overtreatment side of life,” he said.
But the founding president of The Indian Thyroid Society, R. V. Jayakumar, MD, DM, who has been on Abbott’s speaker bureau and advisory board, agreed some doctors are too quick to prescribe levothyroxine.
“So many people are unnecessarily treated,” he told MedPage Today in 2013. “A large number of people get their one [TSH] reading and if it’s elevated they are started on treatment.”
News-savvy Indians would be excused if they worried about even slightly abnormal tests.
During “Think Thyroid Month” in 2009, two of India’s major newspapers warned that leaving thyroid disorders untreated could trigger a plethora of serious health problems, including “coma or death.” The stories, based on a press release from the Indian Thyroid Society, a longtime recipient of funding from Abbott India, guided readers to the firm’s campaign website.
Today, the site greets visitors with this message: “One in ten Indians may have thyroid disorder. Are you among them? Click here to find out.” Then follows a long list of “symptoms” such as tiredness, dry skin, constipation, and being older than 35 years. If you tick even one, you’re advised to “Take a simple test to check the possibility of you having a thyroid disorder.”
“The vast majority of cases that will be found will be subclinical,” said Dartmouth’s Schwartz. “There will be cases where the symptoms have nothing to do with the blood test. They’re overpromising. They’re saying there is this host of symptoms that are going to be fixed by this, which is most often not the case.”
The alarming one-in-10 figure also appears in Abbott’s campaign posters and press releases. It comes from the 2013 survey, which was published in the Indian Journal of Endocrinology and Metabolism and has been cited 40 times according to Google Scholar.
The study was designed like this: In eight major cities across India, residents were invited to participate in a number of general “health camps” — popular one-off events that offer free medical care and sometimes drug samples. Visitors who consented had their blood drawn. The researchers then added up the number of people with lab-defined overt hypothyroidism and those who said they were already taking levothyroxine (the majority).
That could inflate the prevalence of hypothyroidism because some people might be treated for subclinical disease, according to Brito, the Mayo endocrinologist.
The bigger problem, though, is that health camps in India attract sick people wanting to get checked out. That would help explain the paradoxical result that 11% of participants had hypothyroidism, while only 8% had subclinical hypothyroidism.
“The completely bogus way of sampling swamps any other considerations,” McMaster’s Guyatt said. “This tells you absolutely nothing about the frequency of thyroid problems in the Indian population.”
The Abbott spokesperson told MedPage Today the study is “based on sound clinical principles” and was “designed under the guidance of a scientific committee consisting of leading endocrinologists in India.”
The lead author of the report, who at the time was associate editor of the journal that published it, is A. G. Unnikrishnan, MD, DM, chief executive officer of Chellaram Diabetes Institute in Pune. He told MedPage Today by email that the survey’s “sampling methods were developed by an independent statistical agency, and approved by scientific experts involved in the study.”
But he acknowledged that “health camp-based studies show more prevalence of disease as more sick persons report for them.”
To Brito, the case is clear. “They are spinning the numbers, there is no question about it,” he said. “These people are very smart, they know how to create a disease.”