Two weeks ago, the prestigious medical journal Lancet retracted a 1998 article that purported to show a link between childhood vaccines and autism. The article stimulated a decade-long debate about vaccine safety, and the Lancet’s retraction effectively ended reasonable scientific discourse on the subject: the vaccines are safe.

Ten of 13 authors of the paper had issued a partial retraction 6 years ago, but the first author, Andrew Wakefield, did not. 

Wakefield’s study had focused on 12 children that had gastrointestinal problems. Eight had symptoms that their parents or a doctor thought were caused by the MMR vaccine, and 9 exhibited autistic behaviors.

That study triggered widespread concern that measles-mumps-rubella vaccine caused autism. Parents decided against immunizing their children as a result. Roughly 2.1% of US children weren’t immunized with the MMR vaccine in 2000, nearly triple the rate of 0.77% in 1995, according to a study in Pediatrics.

This occurred despite the publication of several subsequent studies which showed that vaccines were safe. The most notable among these were a 2004 review of the literature by the Institute of Medicine and a 2008 study by the CDC which looked specifically at children with GI problems.

“This retraction by the Lancet came far too late,” Paul Offit, chief of infectious diseases at Children’s Hospital of Philadelphia told the Wall Street Journal. “It’s very easy to scare people; it’s very hard to unscare them.”

The Lancet pulled the plug after a UK-based health care regulator concluded the Wakefield study was bogus. The General Medical Council’s report included allegations of ethical violations by some investigators, including “cherry-picking” children for the study, rather than taking kids as they presented randomly to the hospital, as had been implied in the paper.

The year-long tailspin in venture-based activity ended on an up note, according to Dow Jones VentureSource. In Q4, 2009, venture investors invested $6.3 billion in 743 deals, up slightly from the $6.1 billion invested in 619 deals during the previous fourth quarter.

Overall, there were 2,489 deals completed and $21.4 billion in venture capital invested in 2009 in US companies. That represented a 31% drop from 2008, when $31 billion was invested in 2,817 deals.

“Venture capitalists are still treading lightly when making investments,” said Jessica Canning, global research director for Dow Jones VentureSource. “In the fourth quarter, venture deal activity returned to levels seen before the collapse of the financial markets, but capital invested continued to lag as investors gave companies just what they need to reach the next milestone.”

2009 was also notable in that for the first time ever, the healthcare industry raised more VC capital than the Information Technology (IT) sector. Healthcare deals garnered $7.7 billion across 701 deals last year, a 14% drop from the previous year. That compared favorably to IT, in which VCs risked $6.1 billion in 817 deals last year, a 35% drop from 2008 and the industry’s weakest year since 1996.

The majority of VC money in health care went to biopharmaceutical companies, which raised $4.2 billion over 302 deals. Medical devices came in second at $2.9 billion for 291 deals.

The Energy & Utilities sector experienced a profound decline in VC investment last year. Companies in this sector raised just $1.2 billion in 87 deals in 2009, less than a third of the amount raised in 2008.

The median round size of venture deals in 2009 was $4.7 million, down from $6 million in 2008, according to VentureSource. Later-stage deals accounted for the largest slice of deal activity, attracting $11.4 billion in investment, whereas seed- and first-round deals garnered $3.7 billion.

Billy Tauzin, Big Pharma’s top lobbyist,  is calling it quits amid growing uncertainty regarding the national effort to reform health care, an effort he supported.

Tauzin reigned for 5 years as president of the Pharmaceutical Research and Manufacturers of America.

Last June, he bet health reform would happen and decided to cozy-up to the Democrats.

In particular, he cut a deal in which drug makers agreed to contribute $80 billion in savings over 10 years by reducing the prices of certain drugs and closing the “donut-hole” coverage gap for Medicare beneficiaries.

Soon after that, the Big O stopped advocating for the importation of cheap drugs from Canada and stopped saying the feds should negotiate Medicare drug prices directly with drug makers. He had held these positions during the presidential campaign.

The Democrats’ health reform bill also guaranteed 12 years of sales exclusivity for BioTech drugs, which is longer than many Democrats and the generic industry preferred.

Of course, all this is in limbo right now.

Tauzin’s deals with the Obama administration drew fire from business representatives and Republicans. Notably, House minority leader John Boehner called his White House deal a “short-sighted” bargain with “Big Government.”

According to Thomas Donohue, president of the Chamber of Commerce, Tauzin improved his industry’s image during his reign. When he took over, Big Pharma was reeling from drug recalls and problems with popular drugs linked to death, diseases and suicide. “Billy stabilized the drug industry,” Donohue told the Wall Street Journal.

Tauzin, a former congressman from Louisiana, collected a $2 million salary from PhRMA. His last day is June 30.

Fourteen states have legalized marijuana for medical uses and the Department of Justice has announced it will not prosecute people who use marijuana while under a doctor’s care and in accordance with state rules.

But even as the regulatory landscape clears, the medical issues associated with smoked marijuana remain muddled. Scientists simply don’t know how effective it is as a therapeutic agent. Remarkably, the literature contains fewer than 20 randomized trials of smoked marijuana for all therapeutic indications combined.

Among these, research findings that support using marijuana for neuropathic pain are probably the strongest. For example, in a trial of AIDS patients published in Neurology, scientists found that 52% of those who smoked marijuana reported at least a 30% reduction in pain, as compared with 24% of those who smoked placebo cigarettes.

Smoked marijuana has also been shown to have a modest anti-nausea effect in cancer patients receiving chemotherapy, and to improve appetite and trigger weight gain in HIV-positive patients.

That said, marijuana has not been shown to help patients with a variety of other conditions ranging from epilepsy to immune system disease.

The muddled situation is further complicated by the fact that the FDA doesn’t regulate marijuana. That means, among other things, that the potency of products available in medical-marijuana dispensaries is likely to vary.

“It’s difficult to understand how we can call it medicine if we don’t know what’s in it,” Stephen DeAngelo told the Wall Street Journal. DeAngelo runs a medical-marijuana dispensary in Oakland.

Marijuana, it must be noted, has been associated with palpitations, memory loss, anxiety, psychotic experiences and, yes, an inability to concentrate.

It also carries a risk of physical dependence, though it is not as addictive as nicotine or alcohol. Smoked marijuana may also irritate bronchial tissue, but a study in Cancer Epidemiology, Biomarkers & Prevention found no link between smoking marijuana and lung cancer.

Australian scientists have found a correlation between the time spent watching TV and all cause mortality. What is more, the relation holds even among people who exercise regularly. The problem, it seems, is prolonged inactivity.

To reach this surprising conclusion, David Dunstan of Melbourne’s Baker Heart and Diabetes Institute followed 8,800 people who were at least 50 years of age for 6 years. 284 of them died during the study, including 125 from cancer and 87 from cardiovascular disease.

Dunstan found that all cause mortality risk increased by 11% for each hour watching TV per day. The findings held up after adjustments were made for exercise duration, gender, age and waist circumference.

People who watched TV at least 4 hours per day were 46% more likely to die of any cause and 80% more likely to die of cardiovascular disease than those who watched 2 hours per day or less.

“It’s not the sweaty type of exercise we’re losing,” Dunstan told the Wall Street Journal. “It’s the incidental moving around…utilizing muscles that [doesn't happen] when we’re plunked on a couch in front of a television.”

The findings likely apply to other sedentary activities like sitting in front of a computer, driving or reading.

“The implication of these findings is that the extraordinary amount of sitting can undo the good effects that we know are a benefit when we get regular exercise,” Dunstan told the Journal.

A recent study by Neilson Co. found that Americans watch 5 hours of TV per day, on average.

Simple strategies to combat the problem include incorporating household chores like folding laundry into TV-time or (god forbid) getting up to change a TV channel rather than using a clicker.

The article appears in Circulation.

Many people know that regular physical activity can reduce perceived stress, blood pressure, LDL (bad) cholesterol levels and the risk of Type 2 diabetes.

It turns out there are many more benefits than that.

For example, regular exercise can increase the body’s capacity to prevent viral and bacterial infections, and boost the body’s response to the influenza vaccine, making it more effective.

 It probably reduces cancer risk as well.

David Nieman, of Appalachian State University has published several randomized trials showing for example that people who walk briskly for 45 minutes, 5 days per week have fewer and less severe upper respiratory tract infections, and 25-50% fewer sick days than sedentary controls.

“No pill or nutritional supplement has the power of near-daily moderate activity in lowering the number of sick days people take,” Nieman told the Wall Street Journal.

Other studies suggest that regular exercise reduces breast cancer risk by 20-30%, and that for patients with hormone-responsive breast cancer, walking for 3-5 hours per week cuts mortality in half.

Still other research shows that exercise retards aging processes like telomere shortening. Telomeres are DNA strands at the tips of chromosomes. When they become too short, cells can’t divide and trigger biochemical processes associated with aging, cancer formation and death.

Two years ago, the Department of Health and Services issued national exercise guidelines for the first time. The guidelines recommend 2 ½ hours per week of moderate aerobic exercise, or 1 ¼ hour per week of vigorous exercise. The guidelines say that additional health benefits accrue to those who double these amounts. They also call for muscle-strengthening activities at least twice per week.

According to the CDC, 36% of US adults undertook no leisure-time physical activity in 2008.

An expert panel has advised the Food and Drug Administration to green light Crestor, AstraZeneca’s cholesterol-buster, for a wider role in the prevention of cardiovascular disease. FDA acceptance of the panel’s recommendations could markedly increase utilization of Crestor and drugs like it.

The recommendation follows release of data from the so-called Jupiter trial, which was sponsored by AZ. In Jupiter, Crestor reduced the risk of heart attacks in apparently healthy adults with no prior history of cardiac disease and normal cholesterol levels.

Participants in Jupiter did have elevated levels of C-reactive protein (CRP), a non-specific marker for inflammation that identifies people at risk for cardiac events regardless of their cholesterol levels.

Jupiter participants who took Crestor experienced a 54% reduction in the risk of heart attack and a 48% reduction in the risk of stroke. They were 46% less likely to require angioplasty or coronary bypass surgery and had 20% lower mortality from all causes.

In reaching its decision, the expert panel noted that Crestor patients developed diabetes at a higher rate than the placebo group, and experienced more deaths due to GI disease and more episodes of mental confusion. But the panel felt these events were due to chance rather than Crestor itself.

AZ wants the FDA to authorize a discussion of the Jupiter study on Crestor’s label, since this would permit the company to market Crestor to a much wider patient population.

Crestor already generates $3.6 billion in annual revenues for AZ, which is good for 9% of the US market. Pfizer’s Lipitor (27%) and generic statins (49%) have the lion’s share of this market.

Both Lipitor and the generic simvastatin have been shown to lower CRP levels. It is estimated that the label modifications would apply to about 6 million US patients.

More than half of American adults, 54%, drink coffee regularly. They consume nearly 400 million cups of it each day making its active ingredient, caffeine, by far the most widely consumed drug in the country.

So you’d think we’d have reached some general agreement on how the stuff affects our health by this time, no?

Alas, that’s not the case.

Recent studies of the matter  suggest that coffee has beneficial effects on health. Last month for example, scientists reported that people who consumed 3-4 cups of Joe per day developed Type 2 diabetes 25% less frequently than those who had less than 2 cups per day.

Another group recently reported that men who drank at least six cups per day developed advanced prostate cancer 60% less often than abstainers.

Earlier studies had, in addition, linked coffee consumption to a reduced risk of colon cancer, head and neck cancer, endometrial cancer, cavities, gallstones, Parkinson’s disease, cirrhosis of the liver and Alzheimer’s disease.

On the other hand, many studies show that coffee, and caffeine in particular, raises heart rate and blood pressure as well as homocysteine levels in the blood. The latter is an amino acid that has been associated with stroke and heart disease.  Other studies have linked caffeine to bone loss in elderly women and shown that pregnant women who consume 2 or more cups per day have higher rates of miscarriages and low birth-weight babies.

What explains the confusion? It’s certainly possible that coffee has protean effects on the human body, and a mixed bag of health outcomes. After all, many drugs fall into that category. Another possible reason is that most studies of coffee’s health effects (including the 2 recent ones mentioned above) feature an observational trial design, in which scientists troll large data sets for associations between behavior and health outcomes, without a particular hypothesis in mind at the onset. (more…)

Ever wonder how safe and reliable Granny’s new pacemaker is? In most cases it turns out nobody really knows, because the quality of the evidence used by the FDA to approve these devices is poor, according to a study published in JAMA last week.

Sanket Dhruva and colleagues from UCSF drew these conclusions after examining the premarket approval process (PMA) for 78 high-risk cardiovascular devices that received FDA approval between January 2000 and December 2007.

PMA is the most stringent FDA review process for medical devices. The scientists found that 65% of the PMA applications for devices were supported by exactly one study.

And overall, the quality of the studies was abysmal. Some failed to provide details like the number of enrolled participants. Only 27% of them were randomized and even less, 14%, were blinded (blinded, randomized, controlled trials represent state-of-the-art scientific research).

The scientists concluded that in general, the FDA’s premarket approval process for cardiovascular devices lacked statistical firepower required to control for bias and hence draw valid conclusions.

The scientists understood that it is more difficult to subject medical devices to blinded studies, since there is no way to produce a “sugar pill” (that is, placebo) for medical devices.

“But we were surprised that so many devices were approved on the basis of a single study,” Dhruva told the Los Angeles Times.

The FDA started approving medical devices in 1976. Recently, there has been a marked increase in the number of cardiovascular devices implanted in Americans.  In 2008, 1.2 million people received stents in the US alone. 350,000 people received pacemakers and 140,000 received implantable cardioverter-defibrillators.

The health reform “debate” (such as it is) has highlighted our nation’s PCP shortage, but there’s another area where the demand for MD-level services outstrips supply: pediatricians trained in sub-specialties like gastroenterology, rheumatology, and developmental -behavioral medicine.

NACHRI, the National Association of Children’s Hospitals and Related Institutions recently briefed Congress on the matter, in an attempt to favorably influence the “debate.” 

A recent survey of its members, NACHRI officials said, revealed widespread shortages in multiple pediatric specialties which have forced 90% of member’s facilities to delay appointments.

What is more, members reported that vacancies for specialty pediatricians often remained unfilled for more than a year. The most severe shortages are in cardiology, oncology, hematology and developmental-behavioral medicine.

The latter shortage is of particular concern in light of the recent spike in autism-related disorders. Half the members in the survey reported delays of more than 3 months before getting to see a developmental specialist as a result.

Part of the explanation for the shortage is the woefully inadequate compensation these specialists receive. It amounts to just more than half the haul raked in by their counterparts in adult care.

In this regard, a provision in the House bill which requires Medicaid to pay Medicare rates for office visits would really help, NACRI officials say. NACHRI is also lobbying for increased funding for specialty training and a loan-forgiveness program.

In Pediatrics, specialization requires 2 to 3 years of training after the general pediatrics residency is completed. 

“While most of us are driven into this profession because we love kids, the vast majority leave training with huge debt and the prospect of not making very much money at the end,” John McBride told the Wall Street Journal. McBride is a pediatric pulmonologist at Akron’s Children’s Hospital Medical Center.

Pfizer, the world’s largest drugmaker, has announced plans to pursue aggressive sales growth and market-share targets in China. In doing so, it hopes to take advantage of the nation’s unmet needs for health care which have been prompted by an economic boom and an associated increase in diabetes and hypertension.

In a recent interview with the Wall Street Journal, Pfizer’s Regional President of North Asia Allan Gabor said the company wants to increase sales in China by 25% per year.

“When you look at where we are in China today, even though our growth rate is high, the market share is relatively low. And that’s a function of … the nature of the competition here, and the fact that patent law wasn’t really established until 1993,” Gabor told the Journal.

Pfizer is well positioned in the cardiovascular disease market with the blockbusters Lipitor (for cholesterol) and Norvasc (for high blood pressure). Last month, Pfizer rounded out this portfolio by announcing a deal to help Takeda Pharmaceuticals market Actos, a drug for type 2 diabetes, in China.

Pfizer is already the largest foreign pharmaceutical company on the mainland, yet it controls only 2% of the market. The Chinese pharmaceutical market is remarkably fragmented, with thousands of local players in the mix.

The market for pharmaceuticals in China rose 27% last year, and most forecasters believe it will grow by at least 20% per year in the foreseeable future.

Pfizer’s recent acquisition of Wyeth will help. The latter’s pneumococcal vaccine, Prevnar, was “one of the most successful product launches in China history,” Gabor said. Wyeth also adds the popular vitamin supplement Centrum, and baby formula which became popular after last year’s melamine scare.

Pfizer’s move comes about 2 months after Swiss pharmaceutical giant Novartis announced it will invest $1 billion into an R&D facility in Shanghai.

Swiss pharmaceutical giant Novartis announced last week that it will invest $1 billion into an R&D facility in Shanghai, China.

China’s remarkable economic growth is driving the decision, according to Chief Executive Daniel Vasella.

Company strategists predict China could vault into the top 3 national markets for the company’s products as soon as 2014.

The prediction is based on Novartis’ astounding 30% growth in revenues from China in each of the last several years.

That trend is likely to accelerate now that Chinese officials have decided to overhaul the nation’s health care system, most notably by rebuilding moribund facilities in rural areas and expanding health insurance to 90% of China’s citizens by 2011.

Novartis’ investment will be spread over 5 years. It will boost the headcount in the company’s Shanghai R&D facility from 160 to 1,000, making it more or less equal in size to the company’s A-number one research shop in Cambridge, Massachusetts. The  company’s HQ in Basel remains the largest facility overall.

“I think it will be a signal of China’s rising importance in the pharmaceutical industry,” Vasella told the Wall Street Journal during a recent sojourn to Beijing. “You have to ask yourself, where do you need to be down the road, and clearly it is here.”

Vasella added that his decision was made possible because of the newfound plethora of scientific talent in China. He brushed off concerns about the country’s notoriously lax protections of intellectual property.

Novartis’ move into China is at least the third by a large pharmaceutical company in recent years. Roche opened a research lab there in 2004, and a clinical trial center in 2007.  In 2006, AZ opened a research center in Shanghai. It is building another one in Zhangjiang.

Most of us tend to accumulate stuff of one sort or another, and many of our closets and drawers are hopelessly cluttered. But that’s not the same thing as compulsive hoarding, a psychological affliction that some experts estimate affects nearly 2% of the population.

The homes of compulsive hoarders are stuffed with rotten food and sundry what-have-yous that bury sofas, beds, bathtubs and sinks and block doors and hallways.

Their possessions are disorganized, their bills are frequently unpaid (in part because they are lost in the pile) and their household utilities frequently are cut off as a result…an outcome that exacerbates the squalor.

You may even know a hoarder. “Attorneys, surgeons, business executives—some very bright and successful people have this problem,” according to San Francisco psychologist Michael Tompkins, who has written a book on the subject.

In some hoarders, the behavior is thought to be a manifestation of obsessive-compulsive disorder. In others, the underlying condition appears to be dementia, ADD, PTSD or depression. In still others, the loss of a family member or a job triggers the behavior.

Some hoarders focus their attention on household pets, and cases have been reporting involving 1,000 or more in one home. The hoarders don’t notice the animals are filthy or malnourished, and believe they’re saving the critters from something worse.

What can be done to help such people? Experts say it can be profoundly harmful to forcibly clean up the mess. Hoarders perceive this to be a violation and are bound to repeat the behavior. Better to rely on patience and understanding. 

Professional organizers can help, as can antidepressants and behavioral therapy, but all of these are hit-or-miss at best.

As a last resort, Tompkins recommends “harm reduction” strategies: accept that the behavior will continue and minimize the danger it presents by keeping stairways and doors clear and moving flammable objects from space heaters and stoves.

IBM, one of largest employers in the nation, has decided to waive the $20 co-payments it had charged company-insured employees for visits to their primary care physicians.

Big Blue believes the move can cut its health costs by encouraging people to see their PCPs more frequently which should result in earlier diagnoses and reductions in the number of visits to specialists and ERs.

Randy MacDonald, IBM’s Sr. VP for Human Resources, said the move “is designed to encourage people to get fixed early…we’d rather diagnose a situation and deal with it quickly as opposed to it becoming chronic.”

IBM’s newfound emphasis on primary care is, according to MacDonald, part of its “wellness” strategy which reduces health care costs by preventing illness, or at least treating it earlier. IBM spent $79 million on these programs between 2004 and 2007 and estimates this approach saved the company $191 million.

IBM’s wellness programs pay employees up to $300 per year to take exercise classes or enroll their children in weight-monitoring programs. Soon, it will add a stress relief program to the mix.

“In these economic times, with the loss of home equity and the loss of savings, we are seeing stress-related issues” in employees, MacDonald told the Wall Street Journal.

Helen Darling, president of National Business Group on Health, called IBM’s move “very unusual. The number of employers who cover primary-physician visits without a co-pay is minuscule,” she said.

IBM has 115,000 US employees and spends nearly $1.3 billion per year on their health care. Its benefit practices are watched closely by other employers, and it is known to be a trend-setter in this area.

When the so-called “atypical antipsychotic” drugs hit the market 15 years ago, psychiatrists and PCPs began prescribing them like crazy for schizophrenia and bipolar disorder.

They were motivated the poor side-effect profile of previously available drugs, and encouraged by relentless and occasionally unscrupulous marketing campaigns promulgated by drug makers and paid clinical spokespeople.

Last year, the drugs generated $14.6 billion in US sales alone, according to IMS Health.

Unfortunately, the newer drugs proved to be, at best, marginally more effective than their older, cheaper brethren, and have a nasty tendency to promote weight gain and diabetes, particularly in children—for whom they are rarely indicated, according to the FDA.

Now, Christolph Correll and colleagues at Feinstein Institute for Medical Research have quantified the weight gain problem, and it’s a lot.

According to their report in JAMA, atypical antipsychotic drugs caused youths between the ages of 4-19 years old to gain up to 19 pounds on average in just 11 weeks.

“The weight gain is much larger than we thought,” Correll told the Wall Street Journal. “It’s massive, and it’s the medication” that caused it, he added.

Correll’s study involved 272 youths who were seen at semi-urban, tertiary care, academic inpatient and outpatient clinics. It included the 4 top-sellers in the space: Zyprexa (Lilly), Abilify (BMS), Risperdal (J&J) and Seroquel (AZ). Participants had not taken the drugs previously.

Of the 4, Zyprexa caused the most weight gain—nearly 19 pounds—a 15% increase over baseline. The corpulence was associated with significant increases in glucose and cholesterol levels.

The other drugs caused weight gains between 10-13 pounds on average, and had variable effects on glucose and cholesterol.

The scientists encouraged physicians to be extremely careful when prescribing these drugs to youths and to check their patients’ weight and blood tests every 3 months.

The FDA will soon decide whether to approve these drugs for use in youths. Any bets how that turns out?

When Thai and US Army scientists announced last month that their experimental HIV vaccine reduced the risk of contracting the disease by 31%, it caused quite a stir. After all, every one of the 100 or so previous HIV vaccine trials over the last 20 years had failed completely.

Alas, a second analysis of the $105 million study that was released weeks after the announcement suggests the apparent, moderate benefit may have been caused by a statistical fluke.

Worse yet, it turns out that the results of the second analysis were available to the scientists when they announced their original findings.

“We thought very hard about how to provide the clearest, most honest message,” said Jerome Kim, an Army scientist involved with the study. “We stand by the fact that this is a vaccine with a modest protective effect.”

Kim’s team based its initial announcement on a “modified intent to treat analysis,” which includes all volunteers that enrolled in the study, whether they received the full course of the vaccine or not. Such analyses reflect real world situations in which some people don’t show up for all shots in the vaccine sequence.

Using this analysis, the scientists determined that there was only a 3.9% chance that the observed 31% reduction in HIV among the vaccine-treated group was caused by a simple statistical fluke…in scientific parlance, this is considered to be a borderline significant result.

The second, so-called “per protocol” analysis included just the study participants that received all vaccines in the regimen at the right time.

Such analyses normally corroborate intent to treat findings, but for unknown reasons, it did just the opposite in this study. It suggested there was a 16% chance the results could have been due to chance alone—far too high to support claims that the vaccine was efficacious.

Some AIDS activists and scientists believe the vaccine merits further study, but worry that the botched announcement might undermine support for the vaccine and HIV vaccine trials generally.

“I would have preferred to have seen both results straight up. It might spring back on (the scientists), and that would be unfortunate,” Mitchell Warren, director of the AIDS Vaccine Advocacy Coalition said.