Off-Label Prescriptions – Is FDA's Regulation Sluggish?

Off-label use of medicines, though acceptable, is at times still controversial in the medical world. Sometimes the off-label usage is really warranted, at others times it is rarely warranted. But how efficient is the US food and pharmaceutical drug regulator, “the FDA,” in forestalling inappropriate promotion of off-label drug use?

The well-known phenomenon called “Off-label use,” refers to the practice of writing prescriptions for drug usage that's beyond the approved scope of a pharmaceutical drug. Some examples of such usage include SSRI medication (approved for depression) prescribed off-label to treat men suffering from premature ejaculation, Carbamazepine (an anti-convulsant), used to help individuals with bipolar disorder, and Methotrexate or (MTX), which has an approved use in treating choriocarcinoma, if often prescribed to manage an un-ruptured ectopic pregnancy.

In the United States the approval process requires that the Food and Drug Administration (FDA) be convinced of a drug's safety and effectiveness in treating a disease. Once there's enough convincing evidence, the manufacturer and the FDA formulate relevant language for the drug's label.

The following figure presents the frequency of violations.

However, recently a report compiled by the Government Accountability Office (GAO) brought out the fact that the FDA takes about 7 months to send warnings to pharmaceutical companies promoting potentially harmful for off-label uses of medicines. And it takes yet another 4 months for these companies to take corrective action on the violations.

The prevalence of off-label prescriptions can be assessed by the fact that more than 20 percent of prescriptions for 100 most commonly used drugs were found to be for off label use. Further, 60 percent of randomly selected drug prescriptions were again found to be for off-label use.

So, is the FDA sluggish in regulating undesirable off label use promotion?

Experts believe that it might be to quite an extent, due to the following reasons:

1. It takes about 7 – 11 months on an average to address violations.

2. The FDA doesn't specifically monitor off-label promotion. Rather, it's just a part of a larger number of oversight activities for combating all promotional violations. Further, not all submissions to the agency are scrutinized, hence there's a greater chance for violations bypassing the filter.

3. Its capacity to monitor is not at par with the high volume of materials submitted to it (it received 68,000 final submissions in 2007 itself). For instance, the FDA is only able manage a fraction of the thousands of continuing medical education (CME) activities each year, some of which include complaints from doctors to identify off-label promotions in the form of unsolicited statements from sales persons.

The chart below depicts the increasing caseload of the FDA

4. It doesn't keep a tab on all submissions, or the status of reviews supporting off label use, which gets in the way off regulating potential violations.

5. There isn't a standardized tracking system to manage the reviews.

6. Some violations by their very nature are difficult to track, such as the violative conversations between physicians and pharmaceutical drug sales representatives.

The following picture shows the percentage share of each of the target audiences.

While on one hand the FDA's Sentinel Initiative is a great program, the recently highlighted inadequacies of the system regulating off-label promotion of drugs doesn't seem to be encouraging. On the whole it seems that FDA might need to consider a much needed review of the system aimed at addressing unauthorized off label drug promotion, whether it is for conventional drugs or alternative medicines.

Sick (Man)nequin – A New Way To Train Medics

How would you react if you saw a sweating, bleeding, gasping car crash victim, whose bones are all protruding out following multiple fractures? Sick! To even think about.

This is a fact of life at most Emergency Rooms (ER), however medics manning ERs are not only used to working in such 'picturesque' environs, but their training enables them to act wisely, use the right medical instruments, save lives, and not be overwhelmed by scary scenes.

Apparently, becoming a professional medic only comes with hundreds of hours of training. And more importantly they need to learn to make the right decisions instantly, as even a single slip could mean death. But since, it can be a risky a affair to allow newbies to try their hands on real patients, lifelike mannequins can positively make a good substitute, like the one being used at the University of Portsmouth's Expert Centre.

The Sick & Lifelike Mannequin

It's called the "iStan," which is an eponymous to 'standard man.’ Constructed from the inside out, the Mannequin's anatomy is a precise imitation of a real human skeleton.

The "Man's" various body parts such as the spine, neck, arms and hips can move like that of a human. Moreover, it can cry, blink, can have dilated/contracted pupils, its blood pressure can change, and the internal organs can bleed. He can even produce realistic sounds of lung collapse and bowels.

Other realistic functionalities that render it life like include:

• Blood and body fluids can be loaded on board, so that he can vomit and bleed.
• A lifelike skin can sweat and develop goosebumps.
• Broken bones can protrude right through the skin.
• The body cavity can house a baby to make it into a pregnant ant woman.
• It can even simulate a torn off limb, ugh! With blood profusely oozing out.
• And just pinch the nail to see it turn blue as blood accumulates inside.

An intriguing feature of this sophisticated sculpture is that apart from being wireless, it can be remote-controlled from a distance (50 feet) as well. I think this is quite useful too, because you could have a trainer activate vomiting, change the blood pressure, etc., and suddenly make a case more challenging for a team of trainees, just when they thought that their job was over!

Reportedly, some students are even wary during their first encounter with the simulators because it's realistic. Innovations, do indeed help make budding professionals become more skilled even before they lay their hands or surgical instruments on their first real patient. And this one positively is a nice toy for medics to play with and learn from.

A couple of days back I had covered a research wherein scientists made use of animation to hone surgical skills, see the post: Video Game Surgery – A New Way To Train Surgeons to learn more.

Are Today’s Americans Sadder?

Pathological sadness better known as “depression” might be affecting more people in the USA than before as a much larger number of central nervous system drugs called “antidepressants,” are being prescribed. A recent report from the Agency for Healthcare Research and Quality (AHRQ) highlighted the fact.

Most of us know what it means to feel sad, but it’s the sadness requiring medical attention that causes a significant impairment in a person’s daily life. Some common signs of depression entail feeling worthless, thinking of death or suicide, loss of pleasure in activities that were once enjoyable. In fact statistics reveal that in 2004 about 17.1 million adults experienced major depression within a year.

Depression affects different age groups differently. See below for percentage of people by age groups, who experienced major depression in 2004.

Increasing Use of Antidepressants

However startling it might be, the fact is that between 2002 and 2005, antidepressant prescriptions rose from 154 million to 170 million (16 million more!).

See the graph below:

All of these prescriptions were written by medical doctors for patients consulting them in outpatient settings. In 2005 alone 53 million prescriptions were handed out. Further, in many cases prescriptions were written by doctors other than psychiatrists (doctors who treat mental illness), who only wrote about 29% of them.

The other doctors included General practitioners (GPs) who are primary care providers but are also specialty trained, accounted for 23 percent prescriptions.

The Family practitioners prescribed 21 percent of the drugs. Family practitioners are physicians who’ve undergone a residency in family health care.

The doctors who prescribed the least number of antidepressants were the Internal medicine specialists – who’re doctors with a residency in treating diseases that are often difficult to diagnose by non-surgical means. The prescriptions from these doctors made up for 10 percent of the total.

The chart below summarizes the percent share of specialty doctors:

Given the hike in the prescription of pharmaceutical drugs called "antidepressants," it seems quite likely that an increasing portion of the US population has experienced the blues in the recent past.

Dentists' Drills Are Dying – Thank God!

A dentist’s drill since its inception has been an object of terror for most. While on the one hand technologists strive to improve drill machines, on the other, researchers seem to be trying to eliminate the medical instrument called “dentist’s drill.”

Researchers conducting experiments at the King's College London have made headway to use Raman spectroscopy in detecting tooth trouble so early, that only simple repair work would be needed, thus eliminating the need for a dentist’s drill to even surface. The study has been published in the Society of Chemical Industry (SCI) magazine “Chemistry & Industry.”

The Tooth Troubleshooting Technology

This technology employs the principles of Raman Spectroscopy. Raman Spectroscopy is a technique that has applications in condensed matter physics and chemistry for studying low-frequency modes within a system (rotational, vibrational, etc.) This means that using this technology, scientists can distinguish between different chemicals by assessing the unique fingerprints of molecules within them.

In its proposed dental application, Raman Spectroscopy can differentiate between healthy and decaying teeth, here’s how?

Light rays are shone at a tooth by means of a mini optical fiber. The light then scatters around the tooth based on the tooth’s chemistry. Since different chemicals scatter light differently, by analyzing the patterns produced and comparing them to those found in healthy teeth, dentists can find out the actual health of the teeth. For instance, if the light fired at a tooth encounters bacteria, it would disperse differently than if it doesn’t. Once discovered at an early stage the bad tooth could just need to be treated with special mouthwashes and varnishes to achieve remineralization.

This is a paradigm shift from the current procedures, which rely on either X-rays or visual examination to make the assessment. However, by the time a cavity is diagnosed it’s often too late to avoid the drilling & filling treatment, ugh!

How About The Coziness?

To me everything about a dentist’s drill is scary, just the drill’s sound is enough to make me queasy. And I believe that many others share the sentiment. And when it actually drills through, the sensation is quite memorable. Ouch!

If the newly proposed technology takes over within the next five years, as that’s the time it’s expected to take, then this procedure claimed to be painless shall prevail.

One thing however, which is of concern is that the patient would need to stay stationary till the process lasts for about 30 seconds. Which might need a bit of a practice, but it’s surely better than a painful drilling experience.

The promise of the technology is surely quite encouraging. Till the time it comes to the rescue, I plan to maintain a good dental hygiene, and if need be, not be intimidated by the abominable dental instrument, “the drill.” After all, it does save teeth!

Africa's Innovative Solution to Waste Management!

There's little doubt that the earth is slowly warming. The temperatures, as they rise are bound to trigger climatic changes and lead to newer patterns and prevalence of a number of infectious diseases. And as the efforts to curb environmental pollution continue at international and individual levels, countries depending on their access to resources try to find ways to tackle pollution and ultimately global warming. The following exemplar from Africa is a testament to the trend.

Engineers from the African nation Kenya have devised ingenious tractor trailer systems to serve as waste management equipment.

The invention called the “Ndume Little Pick-up” has come about as a consequence of partnership between the UN organization “UN-Habitat,” and two engineering firms from Kenya to execute work on the Lake Victoria Water and Sanitation Initiative.

The Indigenous Waste Management Process

The Ndume Little Pick-up has a flat deck body and a very low loading height. It facilitates waste management as its flat body can carry eight bins of waste at a time, which is lifted on or off the pick-up manually.

The plan is to let the little pick-ups serve six of the seven towns in the region. To accomplish the task several pick-ups would collect bins of waste from businesses and residential areas and transport them to large containers or other trailers to be eventually carried to the disposal site. From where a waste treatment plant may take over.

This seems to be a noteworthy partnership between the public and the private sector. Further, not only is the program innovative but is also self sustaining, here's how?

When it's about government funded services in under developed countries, it's often the finances which stymie the efforts. However this system would be self-financing, in the sense that the revenue generated from the service provided would be fed back into the system. Thus providing enough funds for the upkeep and manning of the vehicles, which would also lead to regularity of the service.

While the rich nations try to cut back on carbon emissions using sophisticated technology, the not so rich countries invent their own ways to save the environment.

The Power of Naturals Against Cancer

A couple of days back, the USFDA sent letters to several companies asking them to explain their claims about the efficacy of some alternative medicines in fighting cancer.

Though there still doesn't exist a panacea for treating the disease, some promising reports recently published have raised hopes vis-a-vis the power of naturals in arresting the disease.

How wine could help?

Wine, or rather a constituent of the red wine called “resveratrol” could aid in cancer prevention. The ingredient is actually a part of red grapes from which the red wine is derived.

The researchers at the University of Nebraska Medical Center have found that it works by inhibiting abnormal cell growth. Abnormal cell growth is a prime characteristic of many forms of breast cancers. Consequently, the wine's powers could be harnessed to possibly prevent breast cancers.

In fact “resveratrol” is also sold as a dietary supplement, but its effectiveness in suppressing abnormal cell growth has come to light only recently.

A natural substance to the rescue

Cancers can sometimes be quite problematic to treat, as they can stop responding to cancer drugs, or even become resistant to them. But a natural substance “argyrin” has been found to destroy the unwanted tumor cells. This discovery has been published in the journal “Cancer Cell,” and the research was conducted at the Helmholtz Centre for Infection Research.

While, research on naturals has shown promise, an advancement has been registered in conventional medicine as well. For instance a compound called “STF-62247” discovered by the Stanford University researchers has been found to selectively damage cancer cells only, rather than target healthy cells too. Since cancer drugs can sometimes harm healthy cell too, this research published in the journal “Cancer Cell,” is perhaps just the first step towards developing effective cancer therapy with minimal side effects.

So till the time the science of cancer drugs with less side effects is perfected, the promise of naturals in treating cancer is welcome news for sure.

How to Make US$ 3.56634 Million in Pharma Business?

No kidding! One Mr Viraj Shah (37) of UK has done it by dealing in counterfeit drugs. But the only problem now is that he'd be spending a good 51 weeks in prison, face suspension for two years, and pay back the society with 40 hours of community service, as the Kingston Crown Court has convicted the person.

Counterfeit drugs are a menace all over the world, with most of them present in regions where the regulatory and legal systems are frail.

According to the WHO fact sheet on counterfeit drugs:

“Most industrialized countries with effective regulatory systems and market control (e.g. USA, most of EU, Australia, Canada, Japan, New Zealand) have a low proportion, i.e. less than 1% of market value”

“Many countries in Africa and parts of Asia and Latin America have areas where more that 30% of the medicines on sale can be counterfeit, while other developing markets have less than 10%; overall, a reasonable range is between 10% and 30%”

“Many of the former Soviet republics have a proportion of counterfeit medicines which is above 20% of market value — this falls into the developing country range.”

Businesses dealing in pharmaceuticals need to be wary of the crime, not only because it eats into their profits, but also because it can kill thousands of innocents in no time. I think it's integral to a company's social responsibility.

You might want to browse through the resources below for more information on the issue and tips to combat the crime.

Helpful Resources

1. The United States Food and Drug Administration (US FDA)
2. The United Kingdom Medicines and Healthcare products Regulatory Authority (MHRA)
   
3. World Health Organization International Medical Products Anti-Counterfeiting Taskforce — WHO IMPACT

HealthEvent: WA Safety Show 2008

The WA Safety Show 2008 is a new kid on the block featuring most products and services under the sun that you can associate with workplace safety.

The event is to be held in mid August once every two years in Perth, Australia. An insightful conference too is to be organized alongside the trade event, which entails presentations from more than 40 industry experts on Occupational health and safety (OHS). The show is organized by the Australian Exhibitions & Conferences, which is also known for holding similar popular shows around the country, viz. “The Safety Show Sydney.”

Who's likely to benefit from the show?

Ensuring workplace safety and health is a critical component of all industries, however for some it's an absolute must. Some sectors which are more prone to occupational safety issues include manufacturing, mining, building/construction, transport/freight, etc.

About, 150 leading companies from the industry are expected to showcase 1000s of products to help organizations find solutions to ensure occupational health and safety, and statuary compliance. And according to estimates more than 3000 visitors would come to explore the latest innovations and insights in occupational health and safety.

So just about anyone from health care consultants to corporates looking forward to such interactions and insightful events would find it worthwhile. You could be a Health & Safety Manager, Owner, a CEO, Director, a Purchasing Officer, Site Manager, etc.

What's on Display?

Well, there are products, services and even consultants are on display! Just to give you an idea, few of the products pertain to Cold Storage, Communication Devices, Cranes & Hoists, etc. Similarly services entail: Finance & Insurance, OHS Training & Compliance, Health & Safety Consultants.

The Key Details Follow:

Show Name: WA Safety Show 2008

Organizer: Australian Exhibitions & Conferences Pty Ltd.

Venue: Perth Convention Exhibition Centre, 21 Mounts Bay Road, Perth

Dates:

• Tuesday 12 August 2008 10am - 5pm

• Wednesday 13 August 2008 9am - 5pm

• Thursday 14 August 2008 9am - 4pm

Trade Show Website: WA Safety Show 2008

As industrialization gains pace in Western Australia (WA), a greater need is being felt for products and services that would help organizations to ensure safety and health of their workforce. The WA Safety Show 2008 seems to have come just at the right time to address the needs.

If you'd like more information on health care shows and trade exhibitions around the world, here's a good resource that's replete with information on such events almost everywhere, except Antarctica!

The US Healthcare Industry Facing Challenges – Is It?

Over the past couple of days developments on the issue of ensuring patient safety have left the providers of health care in the US scratching their heads.

Just a couple of days earlier the buzz about the congress introducing the legislation on medical device safety (the proposed “Medical Device Safety Act 2008”) was rife, and it still is. The new legislation would enable the medical device manufacturers to be held accountable in cases where medical device causes harm.

And now it's the talk of newer rules that would make getting approvals for diabetes drugs a much longer process than it presently is.

The Medical Device Safety Act 2008 - Implications

The amendment is widely being seen as an instrument that serves as an extension of patient rights and interests. Upto now, once medical devices secured clearance from the FDA, the makers couldn't be sued under state laws. A recent Supreme Court Ruling highlighted the fact wherein the consumers weren't able to seek compensation for injuries, medical expenses, etc. This was because if the manufacturers were sued under state laws then there would be a conflict between the federal and the state laws, which isn't allowed.

With the FDA clearance of medical devices being stripped off its “stairway to heaven” status, the manufacturers would need to introduce many measures to leave no stone unturned in ensuring quality production.

However, a contention was raised that if a patchwork approach is employed for medical device approvals it would lead to conflicting labeling and indications on products.

Further, that more lawsuits and delays in newer technologies reaching patients would eventually raise health care costs.

Diabeties Drugs – Tougher Rules

The issue has caught limelight following a proposal by a renouned cardiologist from the advisory panel in the US, to further test the new diabetes drugs for heart safety.

Reportedly, the drugs could be subject to long term testing, in case short term testing raises red flags. Again, this brings up the issue of diabetes drugs becoming costlier to manufacture, and the extra baggage would naturally be passed on to the consumers.

A second concern is that of quick availability of drugs. Given the present proposal, lag times of upto a year are expected, which could possibly make companies wary of manufacturing diebetes drugs.

So it seems that there are some tough challenges that the American industry is up against. Now, only time will tell how the health care providers strike a balance between economics, legislation and patient safety concerns.