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.

Drugs That Can Land You in the Emergency Room

It’s midnight at the fire station and a call goes out for a patient who has overdosed. In addition to an ambulance and medic unit, police are dispatched.  As we stage for the police, to ensure that the scene is safe, we speculate as to what we’re going to encounter. Will the patient be conscious? What sort of emotional distress has driven them to this? Is it a serious attempt or a cry for help?  Will there be weapons?

As we mentally run through all types of scenarios, it’s doubtful that many of us have considered that our patient will be an 82 year old great grandmother armed with nothing more than her reading glasses and the remote control.

But increasingly that’s what we might find.  As Americans live longer, we have an increasingly frail population suffering from a greater number of chronic conditions, taking more medications than ever before. Among adults 65 years of age or older, 40% take 5 – 9 medications and 18% take 10 or more.

This type of polypharmacy is associated with an increased risk of adverse events. Older adults are nearly seven times as likely as younger persons to have adverse drug events that require hospitalization.

According to a recent article in the New England Journal of Medicine blood thinners and diabetes drugs cause most of the unintentional overdoses that lead to emergency hospitalization in older patients.

Researchers reviewed the records of 100,000 hospitalization events due to major drug side effects in people aged 65 and above from a representative sample of 58 hospitals.  Almost half, (48%) of adverse drug event (ADE)-related hospitalizations occurred in patients older than 80.

The drugs they looked at included prescription and over-the-counter medications, vaccines, and dietary supplements.

Adverse events were categorized as allergic reactions, undesirable pharmacologic or idiosyncratic effects at recommended doses, or unintentional overdoses.  Other effects included problems due to medication-delivery methods (e.g., choking) and vaccine reactions. Visits for intentional self-harm, drug abuse, therapeutic failures, and drug withdrawal were excluded.

Shockingly, just four medications accounted for more than two-thirds of emergency hospitalizations:

Given that emergency hospitalizations caused by ADEs result in significant morbidity and enormous costs it’s not surprising that decreasing harm to patients and reducing costs by preventing re hospitalizations is a goal of the $1 billion federal initiative Partnership for Patients.

Achieving a 20% reduction by the end of 2013 may sound ambitious, but in fact there are a number of simple steps that we can take.

  1. Make sure that everyone taking medications has an up-to-date list, including all prescribed drugs as well as vitamins, herbs, and OTC medicines. Copies of the list should be kept in their wallet and should be shared with all doctors they see so that the potential for drug interactions can be assessed and avoided.
  2. Alert your loved ones that blood thinners and diabetic medicines account for 50% of hospitalizations due to ADEs. Blood thinners and diabetes medications should be regularly monitored by the primary care physician.
  3. Encouraging medication compliance can lengthen a person’s lifespan. Too many times patients stop their medications due to a comment made by a well-meaning friend who has  read something on the Internet. Often the doctor is not informed and the patient may not understand the positive effects of the medication or the dangers of stopping them suddenly.
These small measures may not only save the life of your elderly loved-ones, but they may also  reduce your Word on Health bloggers’ middle of the night 911 dispatches.

Pharma – Cracking Down on Crime

It’s rare in the pharmaceutical industry when a drop in numbers is a sign of good news. Unless it’s fewer side effects, most industry insiders cringe when they hear that this year’s figures are lower than last.

However, SRxA’s Word on Health brings you news of a downward trend that should please all but the most criminal elements of society.

A new report from Freightwatch International shows that the number of thefts of pharmaceuticals significantly declined over the past 12 months.  Not only were there fewer incidents, the average value of each theft was lower.  In total, there were 36 thefts involving shipments during 2011, compared to 49 in 2010. And the average value of lost shipments was $585,000, down dramatically from $3.78 million the year before. Trailer thefts accounted for approximately 90% of the heists. Deceptive pickups and burglaries from warehouses made up the remainder.

This was the first year on record that the pharmaceutical industry did not have the highest value per theft incident. That distinction went to the electronics industry, where the most targeted items were televisions, consumer electronics and cell phones.

Significantly, there were just two pharmaceutical thefts valued at more than $1 million last year. In previous years, the average loss per pharmaceutical theft averaged between $3.5 million and $4 million. Two years ago, medicines worth up to $75 million were stolen from an Eli Lilly distribution center in Connecticut after robbers broke in by cutting a hole in the roof.  That incident resulted in national headlines and prompted the drugmakers  to improve security efforts and tighten the supply chain. Organizations such as the Pharmaceutical Cargo Security Coalition are now dedicated to preventing the theft of medicines in transit.

Nevertheless, pharmaceutical supply chain issues remain a hot topic.

RxPatrol is an initiative designed to collect, collate, analyze and disseminate pharmacy theft intelligence to law enforcement agencies nationwide.

The FDA is also concerned about protecting consumers from the threat of stolen, counterfeit, and diverted prescription and over-the-counter medicines. Stolen products may put consumers at risk because they may not have been stored or handled properly or may have been tampered with while out of the normal supply chain.  An FDA website lists all thefts involving FDA-regulated products that have been stolen either from warehouses or tractor-trailers, and encourages the public to report any suspected criminal activity.

Earlier this month, the US Pharmacopeial Convention (USP) published its proposed general chapter on good distribution practices to ensure pharmaceutical supply chain integrity, for comment in advance of its upcoming workshop due to be held in May 2012.  The aim of the workshop will be to develop best practices to combat counterfeit active pharmaceutical ingredients, excipients, drug products and medical devices that are imported into the USA.

And that can only be a good thing. One of the most harrowing books I ever read was Dangerous Doses by investigative journalist Katherine Eban. In it she exposes a world of criminal activity and corruption and how an increasing number of Americans get counterfeit medicines instead of the real thing.

And while pharmaceutical thefts have not gone away, they are on the decline. For that we must be grateful this Monday morning.

FDA Gets Tough on Asthma Drugs

The U.S. Food and Drug Administration (FDA)  has ordered four drug manufacturers to conduct additional post-marketing clinical trials of their long-acting beta-agonists (LABAs).  LABAs to be studied are AstraZeneca’s Symbicort, GlaxoSmithKline’s Advair Diskus, Merck and Co.’s Dulera, and Novartis AG’s Foradil.

The clinical trials will examine the use of LABAs when used in combination with inhaled steroids. Each of the LABAs plus a corticosteroid will be compared with the steroid alone in patients 12 years of age and older. A total of 46,800 patients will be studied.  Another trial will include 6,200 younger patients, aged 4 to 11, using Advair Diskus.

Last June, the FDA issued warnings on LABAs, saying they should never be used on their own to treat asthma. Although LABAs relax the muscles of the airway to help patients breathe easier, they can cause an increased risk of asthma symptoms that can lead to hospitalizations and death.

The studies will begin later this year, but results are not expected until 2017.

The huge size of the studies signals that FDA wants to be completely sure about the safety profile of these drugs as they are used so widely.

Clearly however, such large study populations might pose financial challenges for the manufacturers.

As of now, Word on Health has heard that Glaxo plans to fully comply with the requirement and Astra Zeneca is finalizing their study protocol with the agency.

Novartis said it was still reviewing the post-marketing requirements issued by the FDA, while Merck said it would have a comment shortly.

We’ll of course bring you updates as they occur.

FDA Criticized by the Government Accountability Office

Normally, it’s  pharmaceutical companies that come under the scrutiny of the FDA.  However, in an interesting twist of fate, the FDA  itself is now under fire for not enforcing its own rules.

Physicians have an innate tendency to trust governing medical entities such as the American Medical Association (AMA), Food and Drug Administration (FDA) and Centers for Disease Control (CDC). Maintaining a reproducible and sustainable standard for reporting clinically relevant pharmaceutical data for new and established drugs has always been a priority for the FDA.

In December 2000, the  FDA issued a call to improve the professional labeling of drug  package inserts and other accredited drug information sources i.e.  the Physician Drug Reference (PDR). In 2006, the standard format for package inserts was modified in an attempt to make it more user-friendly and to serve as an efficient resource tool for patients, physicians, and researchers.

In today’s fast-changing challenging healthcare environment, physicians tend to accept this reported data, and the lack of it, as this is all there is available to them.

However, many would like to know more. For example, how to manipulate a drug dose for a patient with renal failure based on given elimination half life.  Although vital to the management of such patients, all too often, such information is not yet an option for many of FDA approved drugs.

The United States Government Accountability Office (GAO) recently concluded that the FDA lacks a clear and effective process for postmarket drug safety issues. The GAO  also observed that there is a lack of criteria for determining what safety actions to take and when to take them.

This finding is supported by research from  Wesley College, Delaware.   Using the commercially available KnowItAll® informatics platform from Bio-Rad Laboratories, researchers built a Cancer Drug Database containing 85 chemotherapy drugs.  They found that the  reporting of important biological properties such as bioavailability (BIO), plasma protein binding (PPB), elimination half-life (t1/2), volume of distribution (VD), and water solubility were found to be markedly deficient.

According to Malcolm J. D’Souza, Ph.D The evidence is so compelling that the apparent laxity in enforcing reporting regulations for many of these pharmaceuticals is alarming.”

Perhaps the real impact of this research is the red flags it raises.  The FDA guidelines need to be revisited with emphasis on vigilance in reporting all parameters that directly or indirectly affect patient care.

Until the FDA has its house in order, we wonder how much, and for how long either physicians and pharma will continue to trust their own regulatory bodies.  Let us know what you think.