The Doctor Won’t See You Now

US Pharma reps think they have it bad?  Then they should spare are thought for their poor beleaguered colleagues on the other side of the Pond!

According to an article in the industry journal PM Live,  time-pressured doctors in the UK are increasingly refusing to see pharmaceutical sales reps altogether.

A study undertaken by Doctors.net.uk in April 2012 surveyed more than 1,000 General Practitioner’s (GPs). They found that 52% of GPs did not see any pharmaceutical sales representatives in a typical week, while 26% saw only one pharma sales rep during that period.

Lack of time was the most common reason cited by GPs for not seeing pharma sales reps (38%). Other reasons included a practice “no-see” policy and a perceived lack of reps’ impartiality.

At the same time, they learned that doctors are turning to digital channels for independent product information. Nearly a quarter (23%) of the GPs surveyed said they preferred to find their own product information via independent online resources.

Doctors.net.uk said its findings follow earlier studies it conducted that show only 3% of doctors think online pharma resources are credible. Worse still 42% said they never visit pharmaceutical websites.

This research would appear to be in line with other trends among healthcare professionals.  European doctors’ use of iPads and other mobile devices is increasing and US pharma execs expect to increase their future spending on digital marketing channels.

SRxA can help Pharma companies to navigate the promotional maze and get the best bang for those pharma dollar bucks. Contact us today to find out more.

FDA Ad Study: Clarifying the Confusion

As a public health agency, the FDA encourages the communication of accurate health messages about medical conditions and treatment.  One way the pharma industry does this is through non-branded disease awareness communications. These are aimed at either the general public or health care practitioners and discuss a particular disease or health condition, without making mention of any specific drug.  Usually, they encourage consumers to seek, and health care practitioners to provide, appropriate treatment for the particular disease state.

This is helpful for under-diagnosed and under-treated diseases such as depression, hyperlipidemia, hypertension, osteoporosis, and diabetes. Some research has shown that consumers prefer disease awareness advertising. It’s considered more informative and less persuasive than full product advertising.

The pharma industry likes it too.  Disease awareness communications are not subject to the regulations and restrictions mandated by the FDA for prescription drug advertising.

But now, the FDA is concerned that disease awareness ads might confuse consumers. According to a Federal Register notice issued on June 20, the agency wants to know whether the public can distinguish between product claims and disease information, and how different types of information impact comprehension.

So worried in fact,  the Agency has planned a study entitled, “Experimental Study: Disease Information in Branded Promotional Material” to look into those questions.

The study will examine print ads for three conditions – COPD, lymphoma and anemia.

4,650 American adults will be divided into three groups and asked to review the ads electronically.

  • One group will see information about the disease that avoids discussion of disease outcomes the drug has not been shown to address i.e.  “Diabetes is a disease in which blood sugar can vary uncontrollably, leading to uncomfortable episodes of high or low blood sugar.”
  • Other participants will see disease information that mentions consequences of the disease that go beyond the indication of the advertised product, such as, “Untreated diabetes can lead to blindness, amputation, and, in some cases, death.”
  • A third group will see drug product information only.

Disease information will be presented in different ways. For example, on alternating paragraphs, on separate pages or in different fonts and colors from product claims.

Specifically the study will address whether or not consumers are able to distinguish between claims made for a medication and general disease information when they see an advertisement for a drug.  For example, if an ad for a drug that lowers blood glucose, mentions diabetic retinopathy do consumers  think the drug will prevent the affliction, even if no direct claim is made?

The Agency says: “If consumers are able to distinguish between disease information and product claims in an ad, then they will not be misled by the inclusion of disease information in a branded ad. If consumers are unable to distinguish these two, however, then consumers may be misled into believing that a particular drug is effective against long-term consequences.”

SRxA’s Word on Health looks forward to seeing the results. Given that warning letters have been issued in the past over ads that contain mixed messages, this is an opportunity for the FDA to revisit its stance toward such advertising, reduce consumer confusion and, most importantly, learn how best to disseminate useful health information.

The biggest-selling drug in 2018 will be…

EvaluatePharma, a UK based company specializing in pharma and biotech analysis has been gazing long and hard into its crystal ball.

Having scrutinized the world’s leading 3,500 pharmaceutical and biotech companies they have come up with a list of what, they believe, will be the top 10 selling drugs in 2018.

  1. Januvia       (diabetes) – $9.7 billion
  2. Humira        (arthritis) – $8.2 billion
  3. Avastin        (cancer) – $7.5 billion
  4. Enbrel          (arthritis)  – $7.2 billon
  5. Revlimid     (myelodysplastic syndrome) – $6.75 billion
  6. Prevnar 13  (pneumococcal vaccine) – $6.72 billion
  7. Rituxan         (cancer) – $6.3 billion
  8. Lantus           (diabetes) – $5.9 billion
  9. Remicade     (arthritis) – $5.8 billion
  10. Advair            (COPD)  – $5.7 billion

Surprised?  No conventional molecules, no cholesterol lowering agents, no blood pressure meds and not a single new drug among the top ten.  However, they predict the #11 best seller will be GS-7977 – the much anticipated oral hepatitis C drug from Gilead Sciences .

Not so surprising, given the obesity epidemic sweeping the western world that 2 of the front runners are diabetes drugs. Likewise, given the globally aging population – 3 are for arthritis.

#5 may be a surprise to many. Few people had ever heard of myelodysplastic syndrome before ABC news anchor Robin Roberts announced last week that she has the disease.  Still, it’s predicted number 5 status doesn’t mean that an epidemic is expected – it’s still relatively rare with only 10,000 or so new cases detected each year. Its lofty status on the list is more to do with the price. It costs a staggering $10,000 or so for a 28 day supply of the pills.

Other predictions from the EvaluatePharma World Preview 2018 report:

  • Worldwide prescription drug sales are forecast to total $885bn in 2018 an increase of 3.1% from 2011
  • Over $290bn of pharmaceutical sales are at risk from patent expirations between now and 2018
  • Pfizer was the top company for prescription drug sales in 2011, but  Novartis will top the list by 2018
  • Global pharmaceutical R&D spend forecast will grow by 1.5% per year to $149bn in 2018
  • Anti-coagulants (blood thinners) are set to record highest growth of major therapy categories to 2018

Interesting stuff. But the problem with such long term predictive models is that they are but a snapshot  trying to project out six years.

In reality, life is a movie, with a frequently changing plot. For example if J&J’s canagliflozin can reduce obesity and improve blood sugar levels better than Januvia then the projected No. 1 ranking is suspect, at best.

What happened to the Sun(shine)?

Two years ago, the Physician Payments Sunshine Provision was introduced in response to concerns that undisclosed financial relationships between Pharma and  physicians could unduly influence medical practice and patient care.

As part of the provision, all pharmaceutical companies are required to post payments to physicians of anything more than $10 on their web sites.

This law was based on the premise that transparency in these transactions is of public importance and that disclosure acts as a deterrent against quid pro quo exchanges. It was hoped that physicians would be more reluctant to accept large payments if they were publicly disclosed.  Ultimately it was hoped that such disclosure would bring transparency into the prescribing process.

So has this little ray of federal sunshine changed things?

In an attempt to gain insight, if not a definitive answer, a group of researchers examined a large database for prescription drug claims for statins and antidepressants that were written between July 2003 to March 2009 in a half dozen states, including Maine and West Virginia, which have their own sunshine laws.

In both states, brand-name and generic prescriptions were compared with two other states that do not have sunshine laws in order to determine the extent to which prescribing may reflect disclosure requirements. The analysis examined the change in prescribing, before and after their disclosure laws, and compared those results with the change in prescribing in comparison states over the same period.

The researchers postulated that a difference in prescribing in the disclosure state relative to comparison states would potentially reflect the impact of the disclosure law.

So what did they find?

Although there were some statistically significant differences between brand-name and generic prescribing for one or both types of drugs, overall, the effects were small to negligible.

In other words, there was minimal switching from brand-names to generics among two wildly popular therapeutic categories that were heavily promoted during the time period examined.

Why? The authors speculate that disclosure requirements did not capture all promotional spending by pharmaceutical companies and, while industry payments to physicians may have been disclosed to state agencies, the data may not have been disseminated sufficiently to the public to have an impact.

If the policymakers who passed these measures were hoping for a deterrent effect they may be disappointed,” said the study’s lead author, Genevieve Pham-Kanter, Ph.D., assistant professor in the Department of Health Systems, Management and Policy at the Colorado School of Public Health and research fellow at Harvard University and Massachusetts General Hospital.

Whether these results can or should be used by Pharma as an argument for scrapping the Sunshine Act remains to be seen.

Still, what the study demonstrates is that Congress and the Centers for Medicare and Medicaid Services (CMS) along with hundreds of pharmaceutical companies, will be paying hundreds of millions of dollars each year to implement a law that may not actually have its intended effect.

While transparency is an important goal, the administrative and financial burden have unintended knock-on consequences for Industry-funded research, education, and other scientific activities. , call into question.  America is currently facing a job crisis and has still not recovered from the economic decline.  The pharmaceutical industry provides a significant portion of new jobs and taxes that may help America out of these troubled times.

In light of this study, and the tremendous burdens the Sunshine Act imposes on the numerous stakeholders, Congress should perhaps reconsider the need for a federal sunshine law or come up with cheaper, less onerous alternatives.

Could “No See” docs be doing a disservice to patients?

One of the biggest challenges facing any Pharma rep is the increasing number of  doctors who won’t see them. Every week, more and more physicians are restricting, and some even eliminating, their face time with sales reps.

In fact, the number of doctors willing to see reps has declined by about 20% since 2008.  And while some clinicians chose to do this, others have had it thrust upon them by their institutions or employers who are concerned that medical practice may be unduly influenced by pharmaceutical industry representatives.

Although  “no see” advocates argue that removing commercial influence is better for patients, a new study suggests the practice has downsides too.

This should be good news for the Pharma, who has always maintained that the clampdown on reps amounts to overkill and that more than selling, reps  provide information that can benefit patients.

The study, published in the Journal of Clinical Hypertension, divided medical practices into four categories. Based on the degree of sales representative access to clinicians, they were classified as either very low, low, medium, or high.

The clinical decisions, and prescribing behavior of over 72,000 physicians were then statistically analyzed, with regards to the drugs listed below:

The authors found that after the FDA approved Januvia, docs who had little interaction with reps took longer to write prescriptions than docs whose access to reps was not as restricted. Meanwhile, physicians who rarely, if ever, saw reps were slowest to change their prescribing habits after negative news emerged about Avandia and Vytorin .

Specifically, the study found that docs with very low access to reps had the lowest adoption rates for Januvia. They took between 1.6 and 4.6 times longer to start writing prescriptions after the pill was launched than docs who had low, medium or high access to reps. Docs who had very low access to reps were also 4 times slower than those of their counterparts to reduce their use of Avandia, after the Black Box warning was issued in 2007.  There was also “significantly less” change in the prescribing habits of those who had less access to reps in response to controversial and disappointing trial results released in 2008 for Vytorin, than those with fewer restrictions on rep interactions.

The study authors commented, “These findings emphasize that limiting access to pharmaceutical representatives can have the unintended effect of reducing appropriate responses to negative information about drugs just as much as responses to positive information about innovative drugs.”

George Chressanthis, professor of healthcare management and marketing, and acting director for the Center for Healthcare Research and Management at Temple University Fox School of Business, agrees.

The study affirms simple intuition that when physicians have to make decisions involving complex issues with less than complete information available to them, and where the consequence of a wrong decision is significant… unintended consequences are likely to appear. Policies that promote physician ignorance of new medical information resulting from access limits, run counter to protecting patient health.”

Could increasing, rather than decreasing  sales representative access to physicians lead to better clinical decision making and better patient health? Let us know what you think.

Abbott Gets a Shellacking

Last week, the street.com -a leading online provider of financial news, commentary, analysis, ratings, business and investment content- took a major swipe at Big Pharma, in general, and Abbott, in particular. Under the headline ‘Abbott Helps Big Pharma Look Even Worse’ author Vince Crew, lambasts the drugmaker for its past marketing practices and warns that unless Pharma adheres to a zero tolerance policy for illegal practices, the industry’s reputation will be doomed forever. Here’s a verbatim copy of what he had to say – On May 7, Abbott reached an agreement with the federal and nearly all state governments to pay $1.6 billion in connection with its illegal marketing of the anti-seizure drug Depakote.

And yes, it’s even more despicable because it represents the unfortunate, illegal, unethical, typical temptation of off-label marketing — promoting a product for usage contrary to its approval.

Someone(s) at Abbott thought it a good idea, according to the Justice Department confirmation, to have a “specialized sales force” market Depakote in nursing homes to dementia patients, even though there was no evidence that it was safe and effective for such use. By the way, in the spirit of “someone will always tell,” several employees blew the whistle on the pharma behemoth. No doubt the settlement has caused Abbott investors, stakeholders, competitors and the industry in general, to pause. Before you think Abbott is doomed because of a reprehensible thing like this, 11 days following this settlement, Abbott Laboratories reported better-than-expected earnings as sales surged on its injectable arthritis drug, Humira. So, no tears for Abbott, unless they regard ongoing settlements as business as usual and don’t actively adhere to a zero tolerance policy for illegal practices. In that case, we should weep for the industry as a whole. Time will tell.”

Abbott, has a very different story to tell. In their mia culpa press release regarding the settlement, Laura J Schumacher, Executive Vice President, General Counsel and Secretary says, “The company takes its responsibilities to patients and healthcare providers seriously and has established robust compliance programs to ensure its marketing programs meet the needs of health care providers and legal requirements.” As Mr. Crew says, time will indeed tell. However, everyone would do well to heed the warning. According to Deputy Attorney General James M. Cole, “Today’s settlement shows further evidence of our deep commitment to public health and our determination to hold accountable those who commit fraud. We are resolute in stopping this type of activity and today’s settlement sends a strong message to other companies.”

In the meantime, if any pharmaceutical companies are looking for help to ensure that their marketing practices are compliant, please remember SRxA is here to help.

Prescriptions, Physicians, Patients and Payers: Let the battle commence!

Last week the FDA announced that it wants to remove obstacles to America’s most commonly used drug treatments.  If the Agency gets its way, some drugs used to control chronic conditions, such as high cholesterol, diabetes and asthma may soon be available without prescription.  But in doing so, they have reopened a  big can of worms. One that brings into question the very nature of health reforms, preventative medicine and improved access to healthcare.

Here’s the proposal: The FDA would create a new class of “safe use” drugs. While consumers would not need a prescription, they would still need to get clearance from a pharmacist or from specially designed websites to purchase them.

Battle lines are being drawn! With physicians on one side, and patients, pharmacists, pharma and payers on the other.

Doctors are most definitely not thrilled by the idea. Removing the prescription requirement for an inhaler refill, for example, doctors fear they would be taken out of the loop on everyday care decisions.

Insurers, on the other hand are embracing the move. They recognize that they could save big bucks if physician visits weren’t required for run-of-the-mill complaints and ongoing medication monitoring. They might even save on the costs of the drugs themselves because, depending upon how they’re classified, most health plans don’t pay for over-the-counter treatments.

Pharmacists see it as validation of their expertise and pivotal role in primary healthcare and the pharmaceutical industry, who has repeatedly asked for permission to sell such drugs over-the-counter, must surely be cautiously optimistic.

Even normally conservative regulators are supporting the move. “Greater over-the-counter and behind-the-counter access will lower costs and make healthcare more accessible to consumers,” former FDA commissioner Scott Gottlieb said via Twitter. “It’s a good idea, long overdue.”

Even so, the FDA will have a fight on its hands as it moves to turn its proposal into reality. The American Medical Association lambasted the idea in USA Today, saying that patients need guidance from doctors. The doctors’ association also points out that giving patients more control could complicate coordinating care, such as, tracking all the drugs a patient uses to prevent interactions.

But, as The Washington Post points out, FDA sees the doctor’s visit as a hindrance to care; some patients don’t seek treatment if they have to see a physician first. “Obviously, it’s much easier for you to go to your drug store and pick up an item than it is to make an appointment, take a prescription, drop it off and get it filled,” says Nancy Chockley, president of the National Institute for Health Care Management.

About 20% of prescriptions written in the United States currently go unfilled. Removing obstacles that keep Americans from managing their own health care is, according to one patient, namely me, a good thing.

The FDA contends, and I agree, that some consumers may not even go as far as getting a prescription because of the “cost and time required to visit a health-care practitioner.  Earlier this month, I stood in line at my local pharmacy for thirty minutes to pick up a refill prescription for blood pressure meds. On reaching the end of the line I was told that there was no prescription. The pharmacist called my doctor and the lack of prescription was confirmed. I called my doctor and was told I would need to make an appointment to have the prescription renewed. I pointed out that I had done that one month earlier and that nothing had changed regarding my health. I was then informed that it was a new policy to issue prescriptions on a month-by-month basis rather than provide automatic refills. Even when I pointed out that I have a chronic condition that I’m doing my best to manage and part of that management is the medicine I have been taking for years, they wouldn’t sway. No doctors visit, no prescription.  And the kicker, I couldn’t get an appointment to see my doctor for a week…meaning, I had to go 7 days without blood pressure meds, all so my doctor could better manage my care!

Practicing medication adherence is very hard when your doctor won’t give you medication…and leaves me wondering if this policy change had more to do with revenue generation than improving chronic disease management.

My personal experience aside, at the heart of this discussion is a fundamental disagreement over what role doctors play in managing patient care. The FDA proposal views a trip to the physician as a hindrance to care, whereas doctors see that visit as crucial, especially as chronic conditions become increasingly prevalent.

The FDA proposal is still in formative stages, meaning there’s still a lot of space for this debate to evolve. Where the discussion heads on this particular issue could end up guiding health policy on what role doctors play in managing patient care – and, at what point, the patient takes charge.

I, for one, can’t wait to see how it plays out, assuming of course that I’m not dead from uncontrolled hypertension!

You Can Teach an Old Drug New Tricks

Drug discovery is a laborious process.

From initial discovery of a promising target to the final medication becoming available, is an expensive, and lengthy process. At present, the costs of bringing a single new drug to market is around $1.2 billion, an amount that doubles every five years.

Aside from the cost, it takes, on average, 12 years for an experimental drug to progress from bench through FDA approval to market.

Annually, North American and European pharmaceutical industries invest more than $40 billion to identify and develop new drugs. Even so, for every 5,000 compounds that enter pre-clinical testing, only five, on average, are tested in human trials, and only one of these five receives approval for therapeutic use.

So, it’s hardly surprising that many pharmaceutical companies are choosing to take a closer look at old drugs. Last week, SRxA’s Word on Health brought you news of a host of potential new uses for aspirin.

And aspirin is not alone.  Old drugs often get a surprising second shot at life. In the past few weeks, the news has buzzed about the skin cancer drug – bexarotene – that may cure Alzheimer’s; a common antimalarial drug – hydroxychloroquine – that may help to destroy cancerand, a leukemia drug that inhibits the Ebola virus.

Then, of course, there’s the personal favorite of many women – Latisse.  Originally developed as a glaucoma treatment , it was found to have the desirable side effect of making eyelashes fuller and longer and is now FDA approved for this purpose.

Testing drugs already approved for one use to see if they can treat other conditions, can reduce time and money. Since these known drugs have already undergone toxicology and safety testing, the clinical development program can be streamlined.

Sometimes it’s pure serendipity.

Take Viagra for example. Although these days it’s the stuff of pharmaceutical industry legend , in the early 1990s, it was just a chest pain drug that wasn’t performing very well in clinical trials. So how did the little blue pill go from heart to crotch?  Pfizer was ready to call it quits when they decided to look into one unexpected but common side effect: long-lasting erections. Then came the drug patent and the rest is history.

The discovery that lithium could be used to treat manic episodes in bipolar patients was equally fortuitous. In 1949, Australian psychiatrist John Cade was injecting guinea pigs with urine extracts from schizophrenia patients to try and isolate a compound that caused mental illness. By accident he happened to use a compound with lithium – which at the time was used as a treatment for gout, as the control. Although he didn’t find the compound that caused mental illness, he did find one that treated it!

Back in 2010 we reported on the repurposing of thalidomide. Although the drug caused serious birth defects when it was launched in the 1960’s as a morning sickness pill it has since been found to be useful in reducing severe and frequent bleeding in patients with  hemorrhagic telangiectasia (HHT); in the treatment of patients with newly diagnosed multiple myeloma when taken  in combination with dexamethasone; and for the acute treatment of the cutaneous manifestations of moderate to severe erythema nodosum leprosum

The National Institutes of Health (NIH) recently established The Learning Collaborative (TLC) to study how to more easily repurpose known drugs to treat rare forms of blood cancers.

TLC is a dedicated collaboration between the NIH Chemical Genomics Center (NCGC) and its Therapeutics for Rare and Neglected Diseases (TRND) program, The Leukemia & Lymphoma Society (LLS), and Kansas University Cancer Center (KUCC) to discover and develop new drug therapies for rare blood cancers. TLC is creating a pipeline of new therapies to treat leukemia from both the discovery of new treatments as well as identifying new uses for approved and abandoned drugs.  For example, Auranofin, a drug originally used for rheumatoid arthritis, is now in clinical trials for treating chronic lymphocytic leukemia.

Word on Health will continue to follow the drug recycling trend and bring you news as it breaks. In the meantime if you have noticed any beneficial side effects from the medicines you’re taking, we’d love to know.

Of Mice and Men…and Mental Health

One in five Americans suffers a major depressive episode in their lifetime. Twenty-eight per cent will develop an anxiety disorder, such as post-traumatic stress, phobias, obsessions, or compulsions. Another 15% will fall prey to alcoholism or drug addiction. If you gather 100 people from any square mile on earth, odds are that one will have autism or schizophrenia.

Just about everything we know about drug treatments for psychiatric disorders we learned from mice.  Just how the mouse became our avatar is part tradition and part biological accident. In the past, rats were traditionally used to test experimental drugs. Rats are small enough to be affordable but big enough to make their brains easy to dissect. And they are smarter than mice. You can swiftly teach a rat to solve a maze, for instance, and then test whether your new drug has a side effect of making rats forgetful.

However, rats missed the knockout revolution of the late 1980s. Knockout technology allows researchers to silence, or knock out, individual genes.

With mice, researchers can insert altered DNA in a mouse stem cell, insert the cell in a newly fertilized egg, and insert the egg in a surrogate mother. That egg might develop as a normal mouse or a knockout. The offspring born with knocked-out genes are mated for a few generations to create a pure strain. Once the geneticists perfected these procedures, mice almost instantly assumed the lead role in modeling human mental malfunctions.

These days, you won’t find more mentally ill mice per square mile anywhere than in Bar Harbor, Maine. Mice with anxiety, depression, autism, learning disabilities, anorexia or schizophrenia – they all congregate here. Name an affliction of the human mind, and you can probably find its avatar on this sprucy, secluded island built for America’s richest and most powerful families — including the Rockefellers, the Fords, the Vanderbilts, the Carnegies, the Astors and the Morgans.

The imbalanced mice are kept under the strictest security, in locked wards at the Jackson Laboratory, a nonprofit biomedical facility internationally renowned for its specially bred deranged rodents.

There are no visiting hours, because strangers fluster the mice and might carry in contagious diseases. The animals are attended only by highly qualified caregivers.

But, accurately reproducing a human mental illness in the tiny brain of a mouse is still hugely challenging. The basic structure of a mouse brain is mostly analogous to a human brain.  They have a hippocampus, we have a hippocampus; they have a prefrontal cortex, we have a prefrontal cortex, albeit one that is much larger. We even share about 99% of their genes. But no one would mistake you for a mouse. The mouse is a nocturnal animal with poor eyesight, adapted to fear predators that strike from above. Mice are fundamentally alarmed by light, open spaces, and sudden movements. It is no surprise then, that they manifest depression and anxiety differently than humans do, if they manifest such ailments at all.

You cannot mimic an entire human psyche in a mouse or a rat,” says 
Jacqueline Crawley, a behavioral neuroscientist at the National Institutes of Health (NIH) “Mice aren’t a one-to-one correspondence to humans. But they are better than zero.”

Disorders like depression and schizophrenia are each linked to hundreds of genes. No one gene is likely to make much difference. But genes are only one part of the story. Other clues to human mental health can be found in the neural circuits of mouse brains. By tracing the wiring that connects one brain region to the next, researchers hope to develop more precisely targeted medications.

Many vintage psychiatric drugs, such as Valium, Ritalin, and antipsychotics, were stumbled upon rather than tailor-made to solve a problem. As a result, they are too broad.  They affect more than one type of receptor, on more than one kind of nerve cell, in more than one part of the brain. Many patients decide the cure is not worth the many side effects.

Mice may be the best models we have of psychiatric disorders, but best does not mean great, or even decent. Gerald Dawson, founder and chief scientific officer of P1Vital, a pharmaceutical consulting firm in the United Kingdom, had his heart broken by the mouse mismatch. In the late 1990s, Dawson set out to eliminate the drowsiness from anxiety drugs.The class of drugs he wanted 
to modify, benzodiazepines such as Valium, Xanax, Ativan, and Klonopin, target the GABAa system.

As with most neurotransmitters, the GABAa system is so evolutionarily ancient that it has diversified to serve many purposes. Hence, the brain has six different GABAa receptor types, presumably to perform six different jobs. Dawson had a suspicion that the sleepiness side effect originated from just one of those six receptors. If he could determine which one, corporate chemists could design a molecule that would avoid activating it. He began to make mice.

One by one, he manipulated the receptor genes, breeding a new line of mice each time. With each new strain, he would administer a tiny dose of Valium. If the animals grew drowsy, he knew he had not yet knocked out the right receptor. Knocking out receptor 1 made little difference. Receptor 3 proved too hard to knock out. Receptor 5 seemed to account for the amnesia that people (and mice) experience when they take anxiety drugs. Targeting receptor 2, Dawson identified a chemical that reduced a mouse’s startle response—a measure of anxiety—without impairing its ability to balance. Success!

Or, so he thought. “When these compounds went into humans, they turned out to be just as sedating as the original drugs.”

Dawson blames the mice. “There’s not enough predictability in animal research.”

But, for all Dawson’s frustration with mice, the rodents did yield a couple of interesting drug leads.

That receptor 5 implicated in the amnesia side effect?  An experimental chemical that blocked its action created temporary geniuses: Mice on it were whizzes in the Morris water maze. A drug company is testing the compound to treat people with Down syndrome. And in the process of trying to eliminate drowsiness, Dawson and his team homed in on one of the chemical switches that cause mammals to go to sleep. Ambien locks onto that switch associated with receptor 1.

So, despite the problems, mice remain the undisputed top animal for research on mental health therapies.

Which just goes to show that mice, like us, have minds of their own.

Time to Give Pharma a Break?

The pharmaceutical industry has been under attack again this week. It’s not unusual for people to complain about the price of medicines and the fat profits of pharma, yet even when the industry tries to reduce the payment burden, or provide educational assistance, it is criticized.

First, there was a series of lawsuits filed by several union health plans against eight large drugmakers. They charge that, rather than save consumers money, prescription drug coupons illegally subsidize co-pays for brand-name meds and can actually increase health insurance premiums.

Then the US Department of Veteran Affairs issued a tough ruling on how sales reps can promote drugs to VA medical facilities in the future. One of the new restrictions concerns educational programs. Starting next month, reps will have to submit educational materials for VA review 60 days in advance of any scheduled meeting.  Additionally, materials will be approved only if industry sponsorship is adequately disclosed; if industry-sponsored data is adequately compared with non industry-sponsored data and if materials do not contain a company name or logo.

Both of these developments are worrying.  The pharmaceutical industry is already the most regulated business in the world. Further restrictions will result in fewer incentives to bring new drugs to market and will further stifle innovation.

Not convinced that it’s time to give pharma a break?  Then consider this:

During the Super Bowl, a representative of Eli Lilly posted the on the company’s corporate blog that the average cost of bringing a new drug to market is $1.3 billion. A price that would buy 371 Super Bowl ads, 16 million official NFL footballs, two pro football stadiums, pay almost all NFL football players, and every seat in every NFL stadium for six weeks in a row. This is, of course, is ludicrous.

Ludicrous and wrong!   In fact, the average drug developed by a major pharmaceutical company costs at least $4 billion, and it can be as much as close to $12 billion.

Company N° of approved drugs R&D Spending Per Drug ($Mil) Total R&D Spending 1997-2011 ($Mil)
AstraZeneca 5 11,790.93 58,955
GlaxoSmithKline 10 8,170.81 81,708
Sanofi 8 7,909.26 63,274
Roche 11 7,803.77 85,841
Pfizer 14 7,727.03 108,178
Johnson & Johnson 15 5,885.65 88,285
Eli Lilly & Co 11 4,577.04 50,347
Abbott Laboratories 8 4,496.21 56,202
Merck & Co Inc 16 4,209.99 67,360
Bristol-Myers Squibb Co. 11 4,152.26 45,675
Sources: InnoThink Center For Research In Biomedical Innovation; Thomson Reuters Fundamentals via FactSet Research Systems

However, in all fairness to our Lilly rep, the drug industry has been tossing around the $1 billion number for years. It is based largely on an industry sponsored study by Joseph DiMasi of Tufts University performed 12 years ago. It’s always been a nice number for the pharmaceutical industry because it seemed to justify the idea that medicines should be pricey without making it seem that inventing new medicines is so expensive an endeavor as to be ultimately futile.

But as can be seen from the table above, that figure is badly outdated.

The range of money spent is stunning. AstraZeneca has spent $12 billion in research money for every new drug approved, as much as the top-selling medicine ever generated in annual sales. Bristol-Meyers Squibb spent just $3.7 billion. At $12 billion per drug, inventing medicines is a pretty unsustainable business. At $3.7 billion, you might just be able to make money –assuming it can keep generating revenue for at least ten years.

So, why is the cost of drug development so high?  Well, a single clinical study can cost $100 million, at the high end. But the main expense, and the main reason for the differences noted above, is failure of potential new drugs during their development.

Has this blog helped to change your views on the industry? As always, SRxA’s Word on Health would love to hear from you.