Saturday, July 6, 2013
Thursday, July 4, 2013
Our pediatrician finally suggested that I give my son a melatonin supplement to help reset his sleep cycle. Try it for seven days, he said, but it may take longer. That night, with just 1 milligram of melatonin, my son fell asleep within 20 minutes—and woke up the next morning well rested, at last. It worked just as well the second night.
At bedtime the third night, he asked, "Mommy, can I have my magic pill to fall asleep?" I began to worry: Was I creating a drug-dependent child? Worse, could this experiment have long-term side effects?
Our bodies naturally produce melatonin, a hormone that is released primarily in darkness and helps to regulate our sleep and wake cycles. Insomniacs and jet-lagged fliers have used synthetic melatonin supplements as a sleep aid for years. Now there is a growing—and, to some doctors, worrisome—trend of using melatonin supplements to help restless children sleep.
Sales of melatonin have risen dramatically over the past five years, according to Nutrition Business Journal. Estimates for 2012 put sales at $260 million; in 2007, the market was just $90 million. Melatonin is available over the counter in the U.S., but in the U.K. and several European countries, the hormone supplement requires a doctor's prescription.
A handful of companies market melatonin directly for children's use, offering flavored, low-dose versions of the supplement. One melatonin manufacturer's website even urges parents to "prepare your child for academic success" by getting him or her to sleep. It cites one study that found "students with C's, D's and F's got about 25 fewer minutes of sleep and went to bed an average of 40 minutes later than A and B students."
Melatonin has been used in pediatrics for over 20 years. An article in the Annals of Neurology in 1991 reported that melatonin successfully corrected the sleep-wake cycle of a blind child with multiple disabilities. Since then, numerous studies, mostly short-term and involving special-needs children, have shown positive results. Doctors say the supplement can be critical in regulating the sleep patterns of children with neurodevelopmental disorders like autism, with few, if any, side effects.
Stressed-out parents are giving their kids melatonin to get to sleep, prompting doctors to issue warning over long-term effects. WSJ contributor Jennifer Wallace joins Lunch Break. Photo: Amazon.
Judith Owens, director of sleep medicine at Children's National Medical Center in Washington, has studied melatonin and children. She said that the supplement appears to have a good safety record, not only with special needs children but with healthy children as well, when used for short periods with a pediatrician's oversight.
Still, some doctors say parents are misusing it. "I've never seen such widespread abuse of any drug or therapy in all my years of practice," said Stuart Ditchek, clinical assistant professor of pediatrics at New York University School of Medicine. One mother told him that "she lines up her six healthy children nightly to give them their melatonin pill." Dr. Ditchek believes the supplement should only be used for the most serious sleep and neurological disorders. The concern, he said, is the lack of long-term clinical studies to see how the hormone supplement interacts with other hormones in the body, potentially affecting fertility or sexual development.
"Parents are using melatonin because they are stressed out," said Michael Breus, a clinical psychologist and board-certified sleep specialist who knows parents that have given melatonin to their children for years at a stretch. "They come home late, eat dinner late, and they think they can just flick an on-off switch for their children to get to sleep."
Some parents have made candid online confessions about why they use the supplement. According to one father's review on Amazon, "OK, yes, as parents my wife and I should do a better job starting the bedtime routine earlier, turning off the TV earlier, limiting sweets, etc., etc. Well, for whatever reason, this is not our strong suit. This 1 mg light dosage of melatonin is very helpful winding our kids down and getting them ready for bed."
As soon as our own son started asking for the "magic" pill, my husband and I stopped giving it to him. Two years later, he still suffers from occasional insomnia. But whenever I get frustrated, I think back to what Dr. Ditchek told me. "For thousands of years our children have been falling asleep without the need for pills," he said. "Giving your healthy child a pill to fall sleep is sending him the wrong message—that he needs a pill to do what should come naturally."
Wednesday, July 3, 2013
Outrage over our paltry victories against cancer informs the forthcoming book, "The Truth in Small Doses: Why We're Losing the War on Cancer—and How to Win It," by Clifton Leaf, who wrote a much-discussed essay on the same topic for Fortune in 2004. The title comes from a 1959 pamphlet that tells doctors to trickle out information to cancer-stricken patients, since most of them "couldn't stand" to know the truth: the disease would kill them and there was little that could be done about it. Today, draped in ribbons of every hue, blinded by the promises of targeted therapies and antioxidants, we have, according to Leaf, neglected a basic truth: "'the cancer problem' is, in reality, as formidable a challenge as ever." (Jerome Groopman discussed the progress in cancer cures, particularly immune therapy, in the magazine last year.)
Leaf is not an oncologist, but he became acquainted with the profession at an early age; he was diagnosed with Hodgkin's disease at fifteen years old. In the book's most poignant moment, Leaf orders his father into the corner of his hospital room to atone for having dozed off while sitting bedside. When Leaf woke up the next morning, "the biggest man I had ever known" was still standing in the corner.
As an editor at Fortune, Leaf became enthralled by the promise of Gleevec, an enzyme inhibitor that, since its release in 2001, has proven highly effective at battling chronic myeloid leukemia. Many thought a new age was coming, in which the chaotic spread of cancer would be hindered by drugs that would be precision-targeted to block the replication of rogue cells. It seemed far better than indiscriminately killing both cancerous and healthy cells, as chemotherapy had been doing for the past half-century.
But Gleevec is the exception, not the rule—and C.M.L. is a relatively simple cancer compared to solid-state tumors of the lung, colon, pancreas, or breast. Once they metastasize, most cannot be cured. Those, like Leaf, who have faced cancer have good reason for their impatience: it takes an average of thirteen years to bring a new cancer drug to market. Many of these drugs are pellets fired into cancer's flank. A recent article in the New York Times titled "Promising New Cancer Drugs Empower the Body's Own Defense" hailed a new melanoma drug whose median survival rate was 16.8 months. An editorial this winter in The Lancet, the august British medical journal, put the matter even more bluntly: "Has cancer medicine failed patients? In the words of cancer experts, the answer is yes."
Leaf argues we should be closer to an all-out cure, considering our investment in the effort. The National Cancer Institute receives roughly five billion dollars per year from the federal government. If both public and private investments are to be accounted for, then Leaf estimates the United States spends about sixteen billion dollars a year on cancer research. Nor is there a lack of political will to eradicate cancer, as there is to, say, reducing carbon emissions. Leaf calls it a "bipartisan disease" that a Republican from Alabama would want defeated as much as a Democrat from Illinois. President Barack Obama said in 2009 that he would "launch a new effort to conquer a disease that has touched the life of nearly every American, including me, by seeking a cure for cancer in our time."
In Leaf's telling, oncology is a hidebound field averse to risk, a culture that "has grown progressively less hospitable to new voices and ideas over the past four decades." He yearns for the likes of Sidney Farber, the unorthodox pathologist who invented chemotherapy in the late nineteen forties at Boston Children's Hospital by injecting children stricken with acute lymphoblastic leukemia with aminopterin, which prevents cancer cells from replicating. A hero in Siddhartha Mukherjee's "The Emperor of All Maladies," Farber is largely responsible for the fact that childhood A.L.L. is a manageable disease today. But his methods had a high cost: he disobeyed superiors, conducted his own trial-and-error studies, and foisted unproven drugs on sick, vulnerable children.
What made Farber an iconoclast is that he wanted to cure cancer even more than he wanted to understand it. As he would come to argue, "The three hundred and twenty-five thousand patients with cancer who are going to die this year cannot wait; nor is it necessary, in order to make great progress in the cure for cancer, for us to have the full solution of all the problems of basic research…the history of Medicine is replete with examples of cures obtained years, decades, and even centuries before the mechanism of action was understood for these cures."
Few new bold projects are being funded now, writes Leaf, noting that in 2010, the N.C.I. used the bulk of its two billion dollars in research grants on existing projects. He is as incensed that the same institutions get most of the money, writing that "in 2011, the top 43 research centers got more funding ($12 billion) than did the bottom 2,574 institutions receiving any kind of NIH support." To some, this is the price of science that is both sound and safe. To others, it is a culture of scientific inefficiency, an I.B.M. mindset in a field that desperately yearns for Apple.
Oncologists in the field with whom I spoke agreed with this overall assessment of the War on Cancer. Andrea Hayes-Jordan, a pediatric surgical oncologist at the M. D. Anderson Cancer Center in Houston, told me that "Our strategic attacks are improving, and we are winning some battles, but not the war yet." Silvia Formenti, who chairs the radiation oncology department at New York University's Langone Medical Center, was even more negative in her assessment of the War on Cancer. She wrote to me in an e-mail, "We have managed to make cancer a huge business, and a national 'terror,' but the progress in reducing mortality is quite questionable."
The book suggests some remedies, foremost among them preventing cancer before it strikes. At Stage 0, a cancerous growth can be detected and removed before it has diversified and spread. By the time a tumor is the size of a grape, it has as many as a billion cells. Those cells become increasingly heterogeneous, and once they break through the basement membrane that acts as a final barrier between organs and tissues, they are free to metastasize throughout the body via the bloodstream or the lymphatic system.
The book finds great promise in the chemoprevention pioneered by Dartmouth researcher Michael Sporn, who wants to treat pre-invasive lesions as seriously as full-blown cancers. This seems to fly in the face of the cautious watch-and-wait philosophy popular with many oncologists, who have become convinced (not without reason) that the cure—toxic chemotherapy, high doses of radiation—could be worse than the disease.
However, other than the breast cancer drug tamoxifen and the H.P.V. vaccine—both of which can reduce the risk of getting cancer, not cure the disease—the promise of chemoprevention remains largely unrealized. A recent paper by two preventative oncologists concluded, "There have been numerous chemoprevention trials in the past 10 years, but the number of approved chemoprevention drugs is still quite small."Another recent study on older men with prostate cancer suggested that "watchful waiting" was often the best route, noting that many patients opted for expensive treatments they didn't need, thus leading to impotence and incontinence. And a federal task force ruled four years ago that women should delay getting mammograms until age fifty (ten years later than the previous recommendation) because of the procedure's own potential dangers.
Leaf acknowledges these dangers, and also points out an even more serious problem with chemoprevention: biomarkers that would signal carcinogenesis in its earliest stages have not been found. So while he is correct to highlight the potential promise of a prophylactic approach, Leaf's own description of "the failed biomarker hunt" is, indirectly, a defense of why oncologists today are left with no choice but to wait until the disease develops.
The desire for an accelerated approach to cancer has antecedents in the AIDS activism of the nineteen-eighties. As Mukherjee describes in his book, organizations like ACT UP "made the FDA out to be a woolly bureaucratic grandfather—exacting but maddeningly slow." That had repercussions in cancer medicine, where patients also demanded quicker access to potentially life-saving therapies. Especially en vogue by the early nineties was "megadose chemotherapy" for breast cancer, complemented by a bone marrow transplant. (The original marrow would have been destroyed by the high toxicity of the purported cure.) Yet as Mukherjee notes, by early 2000, the procedure was discovered to have been supported by fictional studies. One of its main proponents, a South African oncologist named Werner Bezwoda, had charmed his fellow practitioners with astounding results that masked the true, fatal dangers of this excessive approach. Mukherjee calls Bezwoda's influential drug trials "a fraud, an invention, a sham," yet he was hardly the lone cheerleader for megadose chemotherapy. Any urge to hasten the War on Cancer—however justified that urge may be—must grapple with the risk of promising anecdotes curdling into hideous truths.
Of course, some approaches are neither terribly controversial nor difficult, at least from a medical standpoint: Debu Tripathy of the University of Southern California's Norris Cancer Center told me that he believes that ninety per cent of all lung cancers could be eliminated through the cessation of cigarette smoking. Studies have shown a link between red meat consumption and an elevated risk of cancer. Here, then, may be cancer prevention in its simplest form.
On the whole, Leaf is much less optimistic than Mukherjee. Surveying the state of cancer medicine as it was in 2005, Mukherjee concludes, "The empire of cancer was still indubitably vast…but it was losing power, fraying at its borders." Surveying some three thousand years of humanity's battle with cancer, Mukherjee's is the more meditative work. Leaf's book is more urgent, more insistent—the voice of a frightened patient who yearns for a cure, rather than of the sober oncologist concerned with getting the science right. "Emperor" is a story; "Truth" is an argument.
Earlier in June, researchers discovered a tumor of the rib bone of a Neanderthal believed to be a hundred and twenty thousand years old. What plagued him then still plagues us today, much as it plagued Atossa, the ancient Persian queen who is believed to have suffered from breast cancer, as well as the London chimney sweeps stricken with scrotal malignancies. This war has been a long one.
Alexander Nazaryan is a writer living in Brooklyn.
Tuesday, July 2, 2013
PORTSMOUTH, Ohio — Prescription pain pill addiction was originally seen as a man's problem, a national epidemic that began among workers doing backbreaking labor in the coal mines and factories of Appalachia. But a new analysis of federal data has found that deaths in recent years have been rising far faster among women, quintupling since 1999.
More women now die of overdoses from pain pills like OxyContin than from cervical cancer or homicide. And though more men are dying, women are catching up, according to the analysis by the Centers for Disease Control and Prevention. And the problem is hitting white women harder than black women, and older women harder than younger ones.
In this Ohio River town on the edge of Appalachia, women blamed the changing nature of American society. The rise of the single-parent household has thrust immense responsibility on women, who are not only mothers, but also, in many cases, primary breadwinners. Some who described feeling overwhelmed by their responsibilities said they craved the numbness that drugs bring. Others said highs made them feel pretty, strong and productive, a welcome respite from the chaos of their lives.
"I thought I was supermom," said Crystal D. Steele, 42, a recovering addict who said she began to take medicine for back pain she developed working at Kentucky Fried Chicken. "I took one kid to football, the other to baseball. I went to work. I washed the car. I cleaned the house. I didn't even know I had a problem."
Ms. Steele, now a patient at the Counseling Center, a rehabilitation center here, remembers getting calls about deaths of high school classmates while working at an answering service for a local funeral home. She counted about 50 women she had known who had drug-related deaths. She believes that had it not been for a 40-day stint in jail for stealing pain pills, she would have been among them.
"I felt like I sold my soul somewhere along the way," said Ms. Steele, whose father was an alcoholic and abusive. "I didn't feel like I deserved to be given a second chance. I thought my kids would be better off without me."
For years, drug overdose deaths in the United States were seen as mostly an urban problem that hit blacks hardest. But opioid abuse, which exploded in the 1990s and 2000s and included drugs like OxyContin, Vicodin and Percocet, has been worst among whites, often in rural places. The C.D.C. analysis found that the overdose death rate for blacks in 2010, the most recent year for which there was final data, was less than half the rate for whites. Asians and Hispanics had the lowest rates.
According to the report, 6,631 women died of opioid overdoses in 2010, compared with 10,020 men.
While younger women in their 20s and 30s tend to have the highest rates of opioid abuse, the overdose death rate was highest among women ages 45 to 54, a finding that surprised clinicians. The range indicates that at least some portion of the drugs may have been prescribed appropriately for pain, Dr. Nora Volkow, director of the National Institute on Drug Abuse, said in an interview. If death rates were driven purely by abuse, then one would expect the death rates to be highest among younger women who are the biggest abusers.
Deaths among women have been rising for some time, but Dr. Thomas R. Frieden, the C.D.C. director, said the problem had gone virtually unrecognized. The study offered several theories for the increase. Women are more likely than men to be prescribed pain drugs, to use them chronically, and to get prescriptions for higher doses.
The study's authors hypothesized that it might be because the most common forms of chronic pain, like fibromyalgia, are more common in women. A woman typically also has less body mass than a man, making it easier to overdose.
Women are also more likely to be given prescriptions of psychotherapeutic drugs, like antidepressants and antianxiety medications, Dr. Volkow said. That is significant because people who overdose are much more likely to have been taking a combination of those drugs and pain medication.
Broader social trends, like unemployment, an increase in single-parent families, and their associated stressors, might have also contributed to the increase in abuse, but they are slow moving and unlikely to be a direct explanation, Dr. Volkow said.
Stella Collins, who runs group therapy sessions at the Counseling Center, said her patients, most of whom are poor, feel trapped. They are squeezing a living out of tiny paychecks. Many get no financial support from the fathers of their children and come from families where alcohol or drugs were abused. Their feelings of inadequacy and shame over not properly caring for their children help drive their addictions, she said.
"Poverty is depression, it's failure, it's sadness, it's low self-esteem," said Ms. Collins. Her mother, an addict, died of a heart attack at age 56 after spending money meant for heart medication on pain pills, she said.
"These women are stuck, emotionally and financially," Ms. Collins added.
But some of the women also fight their way back.
Kathy Newman, 35, who started using pills in her 20s, after her older sister overdosed, and whose oldest son was born addicted, has been drug-free for two years. She now takes classes, and travels around the county telling her story at schools.
For Ms. Steele, the most motivating image is that of her 12-year-old son's face streaked with tears, looking at her through the glass of the prison visiting area. Her eldest son now has custody of him.
"I was at a big stop sign and it was like, 'O.K., which way are you going to go?' " she said.
Portsmouth has worked hard to stop addiction. Easy access to prescription pain pills has been shut down. Mothers of dead addicts give talks at schools. And while Ohio's death rate from overdoses, like the national rate, is still climbing, the rate in Scioto County, where Portsmouth is located, has declined in recent years, according to the city health department.
Ms. Collins works with women in group sessions, teaching them how to like themselves again.
"Watching them die is the hardest part," Ms. Collins said. "You sit in this room and you don't know who's going to make it."
Monday, July 1, 2013
When I returned home from my recent road trip, a letter from Blue Cross Blue Shield of Illinois (my health insurance company, also known as BCBSIL) was waiting for me. Even though I already knew they denied my appeal for last September's biopsy, I was amazed at how quickly I transitioned from tired but happy traveler to enraged cancer patient.
The upshot of their message was this:
"You already have metastatic lung cancer. A biopsy won't change the fact that you're going to die from cancer."
The statement probably came from the independent "physician who specializes in Internal Medicine/Pulmonary Disease" who reviewed my appeal. You can judge for yourself whether I'm overreacting from this excerpt. I bolded some words for emphasis.
" … in this case the member is already known to have progressive Stage IV Bronchogenic carcinoma even after therapy. Specifically identifying the histopathology of this right upper lobe lesion is not going to affect long-term health outcomes."
Boy, do I feel special.
A Bit of Background
Up till now, I really couldn't complain about my insurance coverage. I'm fortunate enough to have Boeing Traditional Retiree medical insurance through my husband, and it's paid for almost everything related to my cancer diagnosis and treatment (except for 10 cents of each carbo-taxol chemotherapy — go figure). I thought I had the gold standard of enlightened coverage.
After my first recurrence of cancer, which gave me my stage IV determination in October 2011, a large ugly tumor grew fast above my right collarbone. It was 3 inches long after about 2 months. In January 2012 I started second line chemo — 6 rounds of Alimta-Avastin which shrunk the tumor almost 90% — followed by radiation.
Six weeks after this second line treatment, a PET-CT scan showed the little sucker was dead. However, two new nodules had formed in my formerly-clear right lung. The nodules glowed hot enough on the PET scan to make them highly suspicious for cancer, but only a biopsy could determine whether the nodules were cancer, radiation pneumonitis (lung inflammation) or BOOP. BOOP stands for Bronchiolitis Obliterans with Organizing Pneumonia, a pneumonia-like condition that sometimes occurs in lung tissue after radiation in nearby tissue. If one or both nodules were cancer, I needed to go back on chemo — probably Alimta, which was effective against my cancer but eventually made me feel like I had the flu for three weeks out of every month. If one or both were pneumonitis or BOOP, I needed to go back on prednisone, an oral steroid with unpleasant side effects. We weren't looking forlung cancer histology, although that would have been interesting info to have. Histology can determine whether a new cancer tumor is the same type of cancer as the patient's previous tumor. A different tumor type might indicate a different type of treatment would be useful.
One of my nodules was too small to biopsy. The larger nodule was not accessible by more common biopsy methods of needle biopsy through the chest wall or endobronchial ultrasound. My pulmonologist recommended using the newer electromagnetic navigation bronchoscopy (EMN) to determine if the nodule were cancer or something else. We knew BCBSIL would probably not pay for the procedure because they have a policy stating EMN is "experimental" for all situations (despite the fact that Medicare pays for EMN and 2013 treatment guidelines list EMN as an acceptable diagnostic). BCBSIL had denied all EMN claims made to date by my hospital.
When BCBSIL denied the claim, I appealed. I explained my treatment history, including that my cancer is aggressive, and we needed to know if the nodule were BOOP or cancer to give me appropriate treatment. My doctor reviewed my letter and wrote a letter of his own to stick in the packet. I included scan CDs and appropriate medical reports.
Evidently that wasn't enough. Because, well, I'm gonna die anyway.
FYI, the biopsy showed inflammation, but no cancer cells. The tumor board thought it was radiation pneumonitis; my pulmonologist wasn't so sure. We tried prednisone for a month, but it had no effect. A follow-up CT one month after the biopsy showed the biopsied nodule was unchanged, while the other nodule had grown by 50%. My pulmonologist and oncologist agreed I needed to restart chemotherapy.
Misinterpreting Long-Term Health Outcomes
What frosts me about this letter is that a "specialist" decided there was no urgency to get a biopsy because it wouldn't change my "long-term health outcome." Did he expect me to go on steroids AND chemo (both of which have a significant impact on quality of life) in case one of them MIGHT work? Or do nothing, since I'm going to die anyway? Well, here's a news flash: we're ALL going to die! The purpose of medicine is to keep us as healthy as possible while delaying that inevitable long-term outcome as long as possible.
Unfortunately, such statements from doctors are not an uncommon occurrence for lung cancer patients. Many members of Inspire's Lung Cancer Support Forum who've been diagnosed with metastatic lung cancer have been told, "There's nothing more I can do."
My biggest frustration is that in my case – and for an increasing number of lung cancer patients — the doomsday doctor is WRONG. I'm a perfect example of a stage IV patient who has a good prospect for years of a reasonably active life despite my disease.
I was lucky to have enough slides from a 2011 biopsy to have the University of Colorado test my tumor for the relatively new ROS1 genetic mutation in my tumor tissue. Because I tested positive for ROS1, I was able to enter a clinical trial for the targeted therapy crizotinib, a drug which inhibits my ROS1-driven cancer. The trial treatment eliminated both nodules and has given me No Evidence of Disease Status for five months. I am once again able to enjoy traveling, writing, and doing things with my family. If I had not had leftover biopsy slides, an EMN biopsy would have been my only opportunity to obtain enough tissue to test for ROS1. Without that ROS1 trial and crizotinib, I might be dead by now.
Doctors who don't keep current on new treatment options and then decide a biopsy "is not going to affect long-term health outcomes" for metastatic lung cancer patients are insuring those patients will die sooner rather than later.
That's not the kind of health insurance I want. Do you?
At a prenatal class in March, she was told about epiduralanesthesia and was given the option of using a birthing tub during labor. To each offer, she had one gnawing question: "How much is that going to cost?"
Though Ms. Martin, 31, and her husband, Mark Willett, are both professionals with health insurance, her current policy does not cover maternity care. So the couple had to approach the nine months that led to the birth of their daughter in May like an extended shopping trip though the American health care bazaar, sorting through an array of maternity services that most often have no clear price and — with no insurer to haggle on their behalf — trying to negotiate discounts from hospitals and doctors.
When she became pregnant, Ms. Martin called her local hospital inquiring about the price of maternity care; the finance office at first said it did not know, and then gave her a range of $4,000 to $45,000. "It was unreal," Ms. Martin said. "I was like, How could you not know this? You're a hospital."
Midway through her pregnancy, she fought for a deep discount on a $935 bill for anultrasound, arguing that she had already paid a radiologist $256 to read the scan, which took only 20 minutes of a technician's time using a machine that had been bought years ago. She ended up paying $655. "I feel like I'm in a used-car lot," said Ms. Martin, a former art gallery manager who is starting graduate school in the fall.
Like Ms. Martin, plenty of other pregnant women are getting sticker shock in the United States, where charges for delivery have about tripled since 1996, according to an analysis done for The New York Times by Truven Health Analytics. Childbirth in the United States is uniquely expensive, and maternity and newborn care constitute thesingle biggest category of hospital payouts for most commercial insurers and state Medicaid programs. The cumulative costs of approximately four million annual births is well over $50 billion.
And though maternity care costs far less in other developed countries than it does in the United States, studies show that their citizens do not have less access to care or to high-tech care during pregnancy than Americans.
"It's not primarily that we get a different bundle of services when we have a baby," said Gerard Anderson, an economist at the Johns Hopkins School of Public Health who studies international health costs. "It's that we pay individually for each service and pay more for the services we receive."
Those payment incentives for providers also mean that American women with normal pregnancies tend to get more of everything, necessary or not, from blood tests to ultrasound scans, said Katy Kozhimannil, a professor at the University of Minnesota School of Public Health who studies the cost of women's health care.
Financially, they suffer the consequences. In 2011, 62 percent of women in the United States covered by private plans that were not obtained through an employer lacked maternity coverage, like Ms. Martin. But even many women with coverage are feeling the pinch as insurers demand higher co-payments and deductibles and exclude many pregnancy-related services.
From 2004 to 2010, the prices that insurers paid for childbirth — one of the most universal medical encounters — rose 49 percent for vaginal births and 41 percent for Caesarean sections in the United States, with average out-of-pocket costs rising fourfold, according to a recent report by Truven that was commissioned by three health care groups. The average total price charged for pregnancy and newborn care was about $30,000 for a vaginal delivery and $50,000 for a C-section, with commercial insurers paying out an average of $18,329 and $27,866, the report found.
Women with insurance pay out of pocket an average of $3,400, according to a survey byChildbirth Connection, one of the groups behind the maternity costs report. Two decades ago, women typically paid nothing other than a small fee if they opted for a private hospital room or television.
In most other developed countries, comprehensive maternity care is free or cheap for all, considered vital to ensuring the health of future generations.
Ireland, for example, guarantees free maternity care at public hospitals, though women can opt for private deliveries for a fee. The average price spent on a normal vaginal delivery tops out at about $4,000 in Switzerland, France and the Netherlands, where charges are limited through a combination of regulation and price setting; mothers pay little of that cost.
The chasm in price is true even though new mothers in France and elsewhere often remain in the hospital for nearly a week to heal and learn to breast-feed, while American women tend to be discharged a day or two after birth, since insurers do not pay costs for anything that is not considered medically necessary.
Sunday, June 30, 2013
PETER DOSHI walked across the campus of Johns Hopkins University in a rumpled polo shirt and stonewashed jeans, a backpack slung over one shoulder. An unremarkable presence on a campus filled with backpack-toters, he is 32, and not sure where he'll be working come August, when his postdoctoral fellowship ends. And yet, even without a medical degree, he is one of the most influential voices in medical research today.
Dr. Doshi's renown comes not from solving the puzzles of cancer or discovering the next blockbuster drug, but from pushing the world's biggest pharmaceutical companies to open their records to outsiders in an effort to better understand the benefits and potential harms of the drugs that billions of people take every day. Together with a band of far-flung researchers and activists, he is trying to unearth data from clinical trials — complex studies that last for years and often involve thousands of patients across many countries — and make it public.
The current system, the activists say, is one in which the meager details of clinical trials published in medical journals, often by authors with financial ties to the companies whose drugs they are writing about, is insufficient to the point of being misleading.
There is an underdog feel to this fight, with postdocs and academics flinging stones at well-fortified corporations. But they are making headway. Last fall, after prodding by Dr. Doshi and others, the drug giant GlaxoSmithKline announced that it would share detailed data from all global clinical trials conducted since 2007, a pledge it later expanded to all products dating to 2000. Though that data has not yet been produced, it would amount to more than 1,000 clinical trials involving more than 90 drugs, a remarkable first for a major drug maker.
The European Medicines Agency, which oversees drug approvals for the European Union, is considering a policy to make trial data public whenever a drug is approved. And on June 17, the medical world saw how valuable such transparency could be, as outside researchers published a review of a spinal treatment from the device maker Medtronic. The review, which concluded that the treatment was no better than an older one, relied on detailed data the company provided to the researchers.
For years, researchers have talked about the problem of publication bias, or selectively publishing results of trials. Concern about such bias gathered force in the 1990s and early 2000s, when researchers documented how, time and again, positive results were published while negative ones were not. Taken together, studies have shown that results of only about half of clinical trials make their way into medical journals.
Problems with data about high-profile drugs have led to scandals over the past decade, like one involving contentions that the number of heart attacks was underreported in research about the painkiller Vioxx. Another involved accusations of misleading data about links between the antidepressant Paxil and the risk of suicide among teenagers.
To those who have followed this issue for years, the moves toward openness are unfolding with surprising speed.
"This problem has been very well documented for at least three decades now in medicine, with no substantive fix," said Dr. Ben Goldacre, a British author and an ally of Dr. Doshi. "Things have changed almost unimaginably fast over the past six months."
Much of that change is happening because of what Dr. Goldacre calls an "accident of history." In 2009, Dr. Doshi and his colleagues set out to answer a simple question about the anti-flu drugTamiflu: Does it work? Resolving that question has been far harder than they ever envisioned, and, four years later, there is still no definitive answer. But the quest to determine Tamiflu's efficacy transformed Dr. Doshi and others into activists for transparency — and turned the tables on drug makers. Until recently, the idea that companies should routinely hand over detailed data about their clinical trials might have sounded far-fetched. Now, the onus is on the industry to explain why it shouldn't.
IN summer 2009, Dr. Doshi received a call from Dr. Tom Jefferson, a British epidemiologist based in Rome. That year, the swine flu pandemic was spreading worldwide, and Dr. Jefferson had been hired by the British and Australian governments to update an earlier review of Tamiflu, a drug produced by the Swiss company Roche, aimed at reducing the flu's severity and preventing more serious complications. He asked if Dr. Doshi wanted to help.
Determining Tamiflu's efficacy had significant economic as well as health consequences. Around the world, private companies and governments — including that of the United States — were stockpiling Tamiflu in case of influenza outbreaks, and their spending accounted for almost 60 percent of the drug's $3 billion in sales in 2009.
The review of Tamiflu was being conducted under the auspices of the Cochrane Collaboration, a well-regarded network of independent researchers, including Dr. Jefferson, who evaluate medical treatments' effectiveness by analyzing all available research.
At the time, Dr. Doshi knew little about clinical trials or even much about the drug industry. But he knew Dr. Jefferson. Dr. Doshi, after receiving undergraduate and master's degrees in anthropology and East Asian studies from Brown and Harvard, had shifted focus and was pursuing a doctorate at M.I.T., studying the intersection of medicine and politics. He met Dr. Jefferson, a prominent skeptic of the flu vaccine, after researching whether the Centers for Disease Control was exaggerating the deadliness of the disease.
"We were both lone wolves in the field of influenza," Dr. Doshi recalled.
Dr. Jefferson had conducted a Cochrane review of Tamiflu's effectiveness a few years earlier, concluding that the drug reduced the risk of complications from the flu. He assured Dr. Doshi and other researchers on his team that the update would be fairly simple.
But just as their work was getting under way, a simple comment arrived on the Cochrane Web site that changed the course of the research and would ultimately fuel a worldwide effort to force drug companies to be more transparent.
The author of that comment, Dr. Keiji Hayashi, had no connection to the Cochrane group; he was a pediatrician in Japan who had prescribed Tamiflu to children in his practice, but had come to question its efficacy. He was curious about one of the main studies on which Dr. Jefferson had relied in his previous analysis. Called the Kaiser study, it pooled the results of 10 clinical trials. But Dr. Hayashi noticed that the results of only two of those trials had been fully published in medical journals. Given that details of eight trials were unknown, how could the researchers be certain of their conclusion that Tamiflu reduced risk of complications from flu?
"We should appraise the eight trials rigidly," Dr. Hayashi wrote.
Reviews by the Cochrane group are known for being among the most thoroughly researched medical analyses available. But in trying to answer the pediatrician's question, Dr. Jefferson realized that there was a flaw: they relied too heavily on the assumption that the articles published in journals accurately represented the results of all clinical trials that had been conducted.
As he tried to track down the authors of the Kaiser study and the two published trials, Dr. Jefferson said he hit dead ends: One author said he had moved offices and no longer had the files; another said he had never seen the primary trial data, instead relying on a summary analysis provided by Roche. All the authors suggested that he contact the company.
"We took it on faith — on trust," Dr. Jefferson, 59, said recently in a phone interview. Dr. Hayashi's question had tested that faith. Dr. Jefferson began typing each new discovery in a private journal he called Hayashi's Problem, which, he said, "charted my transformation from Dr. Jekyll to Mr. Hyde."
Dr. Doshi said that medicine "relies on hierarchies of trust." He added: "A patient is not going to be in a position to review the entire evidence base themselves. But they trust that there is a watchdog out there."
As they dug into the Tamiflu research, Dr. Doshi said, he realized that such a watchdog didn't exist. Instead, he said, "we have partial watchdogs who see part of the full picture." It became his mission to see the full picture.
Having struck out with the authors of the disputed Kaiser paper and the two other published trials, Dr. Jefferson approached Roche itself, asking for the underlying data from the missing trials. But when he declined to sign a confidentiality agreement, Roche decided not to cooperate with the researchers.
Without more complete data about the clinical trials, the Cochrane group decided that it could not include the disputed study that summarized those results. In December 2009, the team reportedthat Tamiflu could not be shown to reduce complications like pneumonia or hospitalizations.
The British Medical Journal, which printed the team's conclusions, also published its own investigation, showing that Roche had hired ghost writers to author some of the articles involving Tamiflu, and that those writers had said they were under pressure to highlight positive messages about the drug. Roche responded that hiring such writers was common industry practice at the time of the articles, and it rejected the idea that they had been pressured to write positively about the drug.
The articles in the British journal created a sensation, and the Cochrane Collaboration's efforts became a cause célèbre. "Everyone knows about publication bias," said Dr. Steven Woloshin, a professor of medicine at the Dartmouth Institute for Health Policy and Clinical Practice and an advocate of more widespread sharing of clinical trial data. "But they just had so much energy and they brought so much attention to it."
The group's efforts seemed to make a difference: After the articles in the British journal, Roche turned over partial copies of study reports, amounting to a little more than 3,000 pages. Then, in 2011, the European Medicines Agency turned over more than 22,000 pages of documents for 19 trial reports to Dr. Jefferson and his team.
The door had been opened. As they read through the records, the researchers discovered the importance of documents called clinical study reports, which are thousands of pages long and contain details as varied as descriptions of trial protocol and design and the ingredients of the placebo pills.
"We used to know that there was a published paper and there were data behind it," said Dr. Fiona Godlee, the editor of the British Medical Journal. "But people haven't talked about these things, like clinical study reports, that are now being talked about a great deal." Last fall, the journal said it would publish the results of clinical trials only if drug companies and researchers agreed to provide data upon request.
In April, Roche said it would make available to the Cochrane researchers clinical study reports for all Roche-sponsored trials of Tamiflu. Dr. Jefferson, Dr. Doshi and their colleagues hope to complete another update to their review of the drug by year-end.
Some said it was a shame that it took this long for the company to relent. "All these years later, and we still don't know if Tamiflu is effective," said Dr. Harlan Krumholz, the Yale cardiologist who oversaw the review of Medtronic's bone treatment. "It's perplexing to have a billion-dollar drug, and you're still not willing to share everything you've got to know whether this thing is effective and safe."
THOUGH the Tamiflu question is not yet resolved, the Cochrane researchers have succeeded in a bigger way: by helping to change the conversation around companies' responsibility to reveal drug trial data.
Drug companies do not always credit the Cochrane Collaboration. In February, Roche followed Glaxo's lead and announced that it, too, would release detailed clinical data to outside researchers, upon request. But Daniel O'Day, chief operating officer of pharmaceuticals at Roche, denied that its pledge had been motivated by the Tamiflu experience. He said Roche has provided data to "thousands" of researchers.
Mr. O'Day said "there were probably errors on both sides" in how the Cochrane researchers and Roche communicated with each other, and said the relationship deteriorated after Dr. Jefferson refused to sign a confidentiality agreement. He said the company was trying to rebuild its relationship with the Cochrane researchers, but that it stood by the safety and efficacy of Tamiflu.
In 2010, Roche commissioned researchers at the Harvard School of Public Health to conduct a re-analysis of Tamiflu clinical data, which largely confirmed the positive conclusions of the Kaiser study.
Mr. O'Day asserted that the company's transparency pledge had arisen from "the call from society in general for greater transparency of the clinical trials that we have." But others say the Cochrane researchers are largely responsible for that call for transparency.
Andrew Witty, Glaxo's C.E.O., said in an interview that his promise to provide detailed clinical data had grown out of a companywide effort, initiated soon after he became chief in 2008, that would "really ensure that we were more in step with where I thought, frankly, society and the world was moving."
Glaxo, moreover, was in need of an image rehabilitation. Last year, it pleaded guilty to criminal charges and agreed to pay $3 billion in fines after the United States Justice Department accused the company, based in London, of failing to report safety data about its diabetes drug Avandia, and of publishing misleading information about Paxil, the antidepressant, in a medical journal. The settlement, which also included civil penalties over marketing of other drugs, was the largest ever involving a pharmaceutical company.
"We don't see any reason for this information to be held out of the public domain," Mr. Witty said, "provided that the people who are interrogating the information are legitimate researchers with a legitimate question to ask."
In a twist, Roche now finds itself on the same side as the Cochrane researchers — and against many in its own industry — in a debate over what kind of data the European Medicines Agency should be making public. On Monday, the agency released a draft policy, expected to take effect next year, in which it would release clinical trial data whenever it approved a new drug. While Roche and Glaxo have supported the policy, the Pharmaceutical Research and Manufacturers of America, a major industry group, and other drug companies have opposed it.
John J. Castellani, chief executive of PhRMA, said the industry had championed open-source efforts to develop better methods for testing cancer drugs, for example. But proposals like those from the Cochrane team and the European agency go too far, he said.
"If you dump onto the sidewalk all the data and you include commercially protected information," he said, "then you're essentially giving to competitors what we invested billions of dollars in."
Others warned that such a policy could discourage drug companies from investing in Europe. "If you, on the other hand, say, 'You guys are bad actors, we want to cut your prices, we want to take your confidential data and share it with any one of your competitors,' you don't get the same feeling of encouragement," Christopher A. Viehbacher, C.E.O. of the French pharmaceutical company Sanofi,told reporters in Brussels on Monday, according to Reuters.
Industry officials and regulators in the United States say the public already has access to vast amounts of information about clinical trials. The basic results of all clinical trials must now be registered in a federal clearinghouse, for example, and the Food and Drug Administration publishes staff reviews and other documents when it approves a new drug. The F.D.A. has said that it is monitoring the developments in Europe but that federal laws in the United States restrict what types of information can be released, particularly data that could reveal personal or commercially confidential information.
Cochrane group members point to the Medtronic study as an example of the value of a neutral perspective.
In 2011, Medtronic awarded a $2.5 million grant to Yale and asked it to oversee a detailed review of trial data for Infuse, a bioengineered material in spinal fusions to treat back pain. The company was facing claims that it had published misleading information about the treatment, and it turned over its data in an effort to address those criticisms. Two teams that examined the data came to similar conclusions: Infuse appeared to be no better than an older treatment, and may pose added risks.
EARLIER this month, Dr. Doshi opened what he hopes will be a new chapter in his quest for greater understanding of clinical trials. He and several other researchers published what amounted to an ultimatum to drug companies: publish your data, or we'll do it for you.
Under the plan, researchers would publish articles summarizing trial results in cases where the underlying data has already been released. In isolated cases, such information has been made public through litigation and Freedom of Information Act requests.
"It's really neat to see a larger opportunity for a larger impact," he said. "Tamiflu just happened to be the lever that opened that door."