NSAID’s in the News (again)

Medication - Over the Counter - otcLet me start by saying, that despite spending the last 20-something years in or around the pharmaceutical industry, I don’t like taking pills. That said, I’m not particularly partial to pain either. So when my knees or back hurts or I’m doubled over with dysmenorrhea, like many other people, I’ll reach for the ibuprofen.

But that may be about to change. Results from a new, large international study of non-steroidal anti-inflammatory drugs (NSAIDs), showed that high doses of them increase the risk of a major vascular event such as heart attack, stroke or death from cardiovascular disease by around a third.

In other words, for every 1,000 people with an average risk of heart disease who take high-dose ibuprofen for a year, about three extra would have an avoidable heart attack, of which one would be fatal, the researchers said.

vioxxThis puts the heart risks of generic NSAIDs on a par with Vioxx – the painkiller that U.S. drugmaker Merck famously pulled from sale in 2004 because of links to heart risks.

The study team from Oxford University in the UK, gathered data, including on admissions to hospital, for cardiovascular or gastrointestinal disease, from all randomized trials that have previously tested NSAIDs.

This allowed them to pool results from 639 trials involving more than 300,000 people and re-analyze the data to establish the risks of NSAIDs in certain types of patients.

In contrast to the findings on ibuprofen and diclofenac, the study found that high doses of naproxen, another NSAID, did not appear to increase the risk of heart attacks. The researchers said this may be because naproxen also has protective effects that balance out any extra heart risks.

Researcher, Colin Baigent stressed that the risks are mainly relevant to people who suffer chronic pain, such as patients with arthritis who need to take high doses of for long periods. “A short course of lower dose tablets purchased without a prescription, for example, for a muscle sprain, is not likely to be hazardous,” he said.

He also warns patients not to make hasty decisions or change their treatment without consulting a doctor.

For many arthritis patients, NSAIDs reduce joint pain and swelling effectively and help them to enjoy a reasonable quality of life,” he said. “We really must be careful about the way we present the risks of these drugs. They do have risks, but they also have benefits, and patients should be presented with all those bits of information and allowed to make choices for themselves.”

Donald Singer, a professor of clinical pharmacology and therapeutics at Warwick University, who was not involved in the study, said its findings “underscore a key point for patients and prescribers: powerful drugs may have serious harmful effects.

In the meantime, I for one, will be revising my pain versus pill-popping habit, or switching to naproxen.

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Born to have Baby Blues?

Mother In Nursery Suffering From Post Natal DepressionIt’ s not clear what causes postpartum depression.  The condition, which is marked by persistent feelings of sadness, hopelessness, exhaustion and anxiety, usually begins within four weeks of giving birth and can persist for weeks, months or even up to a year. An estimated 10 to 18% of all new mothers develop the condition, and the rate rises to 30 to 35% among women with previously diagnosed mood disorders.

Scientists have long believed the symptoms were related to the large drop-off in the mother’s estrogen levels following childbirth, however studies have shown that both depressed and non-depressed women have similar estrogen levels.

Now researchers from Johns Hopkins say they have discovered alterations in two genes that, can reliably predict whether a woman will develop postpartum depression.

genetic link to post-partum depressionThe genetic modifications, which alter the way genes function without changing the underlying DNA sequence, can apparently be detected in the blood of pregnant women during any trimester, potentially providing a simple way to foretell depression in the weeks after giving birth, and an opportunity to intervene before symptoms become debilitating.

By studying mice, the researchers suspected that estrogen induced genetic changes in cells of the hippocampus – the part of the brain that governs mood.  They  then created a complicated statistical model to find the candidate which could be potential predictors for postpartum depression. That process resulted in the identification of two genes, known as TTC9B and HP1BP3.

Little is known about these genes except for their involvement in hippocampal activity. However the team suspects that they may have something to do with the creation of new cells in the hippocampus and the ability of the brain to reorganize and adapt in the face of new environments. Both of these elements are known to be important in mood.

Furthermore, estrogen can behave like an antidepressant, so when it is inhibited, it adversely affects mood.

Postpartum depression can be harmful to both mother and child,” says Zachary Kaminsky, Ph.D., an assistant professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine. “But we don’t have a reliable way to screen for the condition before it causes harm, and a test like this could be that way.”

The findings of the small study involving 52 pregnant women are described online in the journal Molecular Psychiatry.

blood  test + pregnancyThe study involved looking for epigenetic changes tin the thousands of genes present in blood samples from 52 pregnant women with mood disorders. The women were followed both during and after pregnancy to see who developed postpartum depression.

The researchers noticed that women who developed postpartum depression exhibited stronger changes in those genes that are most responsive to estrogen, suggesting that these women are more sensitive to the hormone’s effects. Specifically, changes to the two genes – TTC9B and predicted with 85% certainty which women became ill.

We were pretty surprised by how well the genes were correlated with postpartum depression,” Kaminsky says. “With more research, this could prove to be a powerful tool.”

Evidence suggests that early identification and treatment of postpartum depression can limit or prevent debilitating effects. Alerting women to the condition’s risk factors — as well as determining whether they have a previous history of the disorder, other mental illness and unusual stress — is key to preventing long-term problems.

Research also shows that postpartum depression not only affects the health and safety of the mother, but also her child’s mental, physical and behavioral health.

antidepressants.pregnancy.giIf the results of this preliminary work pan out then a blood test for the biomarkers could be added to the battery of tests women already undergo during pregnancy.  More importantly, the results could help to inform decisions about the use of antidepressants. While there are concerns about the effects of these drugs on the fetus and their use should be weighed against the potentially debilitating consequences to both the mother and child of forgoing them.

As Kaminsky says “If you knew you were likely to develop postpartum depression, your decisions about managing your care could be made more clearly.”

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Pharma Under Fire for Fair Balance Failings

Unfair balanceUh oh! Seems like the Pharma industry is in trouble again.

Research published in the Journal of General Internal Medicine suggests that family physicians receive “little or no information” about adverse effects associated with medicines in the majority of drug promotions made by sales representatives.

In the study, 255 family doctors from urban practices in the US [Sacrameto], France [Tolouse] and Canada [Montreal and Vancouver] answered questionnaires following visits from sales representatives.  The primary outcome measure was “minimally adequate safety information” (mention of at least one indication, serious adverse event, common adverse event, and contraindication, and no unqualified safety claims or unapproved indications).

The findings showed that sales representatives did not provide any information about common or serious side effects, or identify the patients who should not be using the drug, in 59% of the promotions. In Canada, no potential side effects were mentioned for 66% of promoted products, according to the results.

yes no riskThe researchers also indicated that although 57% of the promoted drugs carried boxed warnings from the FDA or Health Canada, serious adverse events were only discussed in about 6% of the sales pitches.

Félicitations to the French reps who provided information on harm for 61% of the promotions, compared to only 34% in Canada and 39% in the US.

Despite this lack of “fair balance” overall, the doctors considered the quality of the scientific information to be good or excellent for 54% of the promotions and indicated that they would be willing to prescribe the drugs 64% of the time.

Laws in all three countries require sales representatives to provide information on harm as well as benefits,” says lead author Barbara Mintzes, Assistant Professor at the University of British Colombia. “But no one is monitoring these visits and there are next to no sanctions for misleading or inaccurate promotion.”

Despite widespread belief by physicians to the contrary, the information provided by pharmaceutical sales representatives has been shown to influence prescribing. Greater exposure to promotion is associated with higher prescribing volume and costs.  And while regulations in all three countries require sales representatives to provide information on the risks as well as the benefits of their drugs, there are differences.  It’s interesting, to correlate the above results with the fact that that France has the strictest information standards, whereas Canada relies on industry self-regulation.

However, across all three countries, the results of this study would appear to question if current approaches are adequate to protect patient health.

The Pharma Industry should take note.  Time to clean up your act before the Government and Regulatory Authorities do it for you.

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Cutting Costs by Cutting Pills

Medical CostsAccording to some disturbing data released yesterday by the CDC, many US adults aren’t following doctor’s orders. And it’s not just the very young or very old, who, it could be claimed,  don’t know any better.

It turns out that adults under the retirement age are twice as likely to skip their prescribed medications in order to save money to save money.

And although spending on drugs is expected to increase an average of 6.6% a year from 2015 through 202, 20% of adults regardless of age, have asked their doctors for a lower cost treatment.

Americans spent $45 billion out-of-pocket on retail prescription drugs in 2011. But, “if you’re not insured or you face high co-payments, you’re going to stretch your prescriptions,” says Steve Morgan, an associate professor at the University of British Columbia’s School of Population and Public Health in Vancouver. “Even among insured populations, there is this invincibility mindset among the very young. Older people are more likely to adhere to chronic therapies over a longer period of time than younger.”

The study also found that 13% of those ages 18 – 64 reported not taking their medications as prescribed to reduce costs compared with 5.8% of those 65 and older.

cut pillStrategies that alter the way adults take their medications include skipping doses and consuming less than the prescribed amount. About 11% of those aged 18 – 64 also delayed filling a prescription compared with 4.4% of those 65 and older.

Uninsured adults were more likely to have tried to stretch their medications than those with Medicaid or private insurance.

But are such savings worth it? Failing to take medication as prescribed may actually increase costs to the U.S. health system, particularly if medication non-adherence results in increased hospitalizations, or complications of chronic diseases.

Anytime a patient chooses not to take drugs as prescribed, the pharmaceutical industry pharma loses sales. A recent study estimated that pharma loses $564 billion globally to non-adherence to drugs. Not surprisingly then, the industry is experimenting with reminders, to increase adherence. Nevertheless, a nudge from a text or a talking pill container might not inspire patients who are penny pinching.

I’d love to stay and chat, but I need to run to the pharmacy to refill my blood pressure meds that I ran out of several days ago!

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An Aspirin A Day…Takes Your Sight Away?

amdSRxA’s Word on Health has frequently reported on the health benefits of aspirin.  So we were more than a little shocked to read a new study in JAMA Internal Medicine which suggested that people who regularly use aspirin may be at increased risk of age-related macular degeneration [AMD].  This eye condition is common  among people age 50 and older and is a leading cause of vision loss in older adults.  AMD gradually destroys the macula, the part of the eye that provides the sharp, central vision needed for seeing objects clearly. 

age-related-macular-degeneration1In some people, AMD advances so slowly that vision loss does not occur for a long time. In others, the disorder progresses faster and may lead to a loss of vision in one or both eyes. The vision loss makes it difficult to recognize faces, drive a car, read, or do close work, such as sewing.

bayer low doseBut don’t go tossing out your Bayer’s just yet!

In this study, researchers at the University of Sydney looked at a large group of  people who took  daily low-dose aspirin as a preventive measure for cardiovascular disease.

Of nearly 2,400 elderly people studied over a 15-year period, 10% were regular aspirin users. Of that group, 25% developed  macular degeneration over that time frame, compared to 9% who developed it but were non-aspirin users.

While these results were statistically significant, more research needs to be done before  recommending that patients stop taking doctor recommended aspirin.   Despite their results, even the researchers admit that there’s just not enough evidence to support stopping aspirin therapy unless a person already has strong risk factors for age-related macular degeneration.

Ophthalmologist Justis Ehlers, MD, agrees, “Aspirin has clearly been shown to have good secondary prevention for different cardiovascular diseasesWe need to sort this out over time to see what it means.

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A Ray of Sunshine?

sunshineIt’s already 15 months overdue and it will be another year still before the information is public, but last week  the government  set out  the final rule for the Physician Payment Sunshine Act (Sunshine Act) in a 287 page document!

The Sunshine Act (passed in 2010 as part of the Affordable Care Act) requires manufacturers of drugs, devices, biologicals, and medical supplies to report all payments and other transfers of value to physicians and teaching hospitals. The rule was supposed to be published in October 2011, but has suffered continuous delays amongst intense lobbying both by groups keen to get the data in the public hands, such as the AARP, and those most affected by it, such as the American Medical Association (AMA).

The final rule announced February 1st, officially puts the Industry on notice. They have until March 2014 to get their payments reporting act together. The U.S. Centers for Medicare and Medicaid Services (CMS), will then input the data, including payment information from August through December of this year, into a publicly available database which, they say, will be online by September 2014.

doctor_bribes_0318And its not only payments to doctors of medicine that have to be reported. Under the definitions of the Act, “physicians” include doctors of osteopathy, dentists, podiatrists, optometrists and chiropractors.

The rule also requires reporting on both the form and nature of payment or transfer of value made by a manufacturer to a physician.

Forms of payment included under the final rule :

  • Cash or a cash equivalent
  • In-kind items or services
  • Stock, a stock option, or any other ownership interest, dividend, profit or other return on investment
  • Any other form of payment or transfer of value

While, nature of payments include:

  • Consulting fees
  • Compensation for services other than Consulting
  • Honoraria
  • Gifts
  • Entertainment
  • Food
  • Travel
  • Education
  • Research
  • Charitable contributions
  • Royalty or license
  • Current or prospective ownership or investment interest
  • Direct compensation for serving as faculty or as a Speaker for a medical education program
  • Grants
  • Any other payment

doctor + moneyAdvocates of the Sunshine Act have long argued that the public needs to know when doctors are getting paid and by who. “You should know when your doctor has a financial relationship with the companies that manufacture or supply the medicines or medical devices you may need,” said Peter Budetti, M.D. CMS deputy administrator for Program Integrity. “Disclosure of these relationships allows patients to have more informed discussions with their doctors.”

This increased transparency is also intended to help reduce the potential for conflicts of interest that physicians or teaching hospitals could face as a result of their relationships with manufacturers.

Relationships between doctors and drugmakers have been brought up in a number of cases when FDA advisory panels have ruled for or against drugs in which doctors had some interest. For example, last year an advisory panel voted 15-11 to support the approval of Bayer‘s Yaz birth control pills, but allegations later surfaced that four committee members had ties to the manufacturer.

Once the bill is introduced, doctors will get 45 days after information is submitted to vet it for accuracy.

physicians_relationship_with_pharma_companThe American Medical Association (AMA) is not happy.  The doctors’ group wants physicians to have more than 45 days to challenge information in the government’s database and add commentary to explain the payments. It also wants some corporate contributions to physicians excluded from disclosure, including sponsorships for educational activities and “indirect” payments, such as unsolicited contributions a company might make to a nonprofit group affiliated with doctors or to physicians’ employers or practices.

AMA president Jeremy Lazarus wants to ensure “the registries will provide a meaningful and accurate picture of physician-industry interactions. It is critical that the final rule provide physicians with a clear way to correct any inaccurate information and not place any substantial administrative burden on physician practices.”

And the AMA is not alone. Unsurprisingly, the Pharmaceutical Research and Manufacturers of America (PhRMA), the primary lobbying group for drugmakers, said that while it supports more disclosure, the new regulations should take into account the importance of context in the publication of physician payment information.

Ethical interactions between biopharmaceutical companies and health-care professionals are essential to maintaining patient trust,” said Matthew Bennett, a spokesman for PhRMA. The principle behind the so-called sunshine provision “is complementary to this belief and it has great potential for helping patients understand the ways in which such collaboration benefits their health and medical innovation,”

What’s your take on this new rule? Is the government helping to let the sun shine in or is this a dark, dark day for doctors and pharma?  Let us know your thoughts.

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Should new drugs wear a ‘Proceed with Caution’ label?

SRxA’s Word on Health was alarmed to read a new study showing that almost a quarter of prescription drugs approved in Canada over 16 years were later slapped with serious safety warnings or yanked from the market for safety reasons. As Canada’s drug safety agency operates much like the U.S. Food and Drug Administration (FDA), the study may reflect the state of drug safety in the United States as well.

When assessing a new drug, regulators at Health Canada and the FDA are entrusted with making critical and difficult scientific judgments that can affect the health of hundreds of thousands of patients in a matter of months after product launch.

And the cost of error may be high given that the number of people exposed to unsafe drugs may be in the millions.

University of Toronto health policy researcher Dr. Joel Lexchin looked at the 434 drug approvals that moved through Health Canada’s drug-safety arm from the start of 1995 to the end of 2010.

About a quarter of the drugs approved in that period received a fast-track deliberation known as a “priority review” which lasts 180 days instead of the typical 300 days.

Lexchin found that drugs approved this way were 50% more likely to end up with safety warnings, compared with drugs approved according to the customary deliberation period.

And while you might assume that the most-risky drugs would be those those fast-tracked for approval for life-threatening diseases such as cancer and HIV, Lexchin discovered they were no more likely to have safety concerns than drugs fast-tracked for less serious illnesses.

That was a surprise, because regulators could be expected to accept some heightened risks when approving new medications to treat serious illness.

In an accompanying editorial, Thomas J. Moore of the Institute for Safe Medication Practices suggests that new drugs should carry special labeling for their first three years on the market, so that doctors are reminded to prescribe with caution.

Getting faster access to newer, less-thoroughly tested drugs is at best a mixed blessing,” said Moore. “For the first three years after approval, new drugs should carry a special warning akin to the black triangle used in Britain. It should be prominent and mean to every physician, ‘New Drug: Caution Indicated.’

That caution may be worth remembering by both physicians and patients when considering switching to new drugs.