There was one registration status in the database that was specific to the FDA and struck me as somewhat odd: “approvable”. At first, I wondered if “approvable” was even a real word. Looking it up in the dictionary, I found that it meant “capable of being approved.” So, I asked myself the following question: if a drug is capable of being approved, why wouldn’t the FDA just approve it? I found solace in the fact that I was not the only one confused by this term - much of the industry was also puzzled as to its meaning.

On August 11, 2008, a new FDA policy went into effect that removed the term “approvable” from the FDA drug review process. The remainder of this article reviews the changes and the impact to the industry.

The FDA’s Drug Review Process - Then and Now

When the FDA receives a New Drug Application (NDA), it has 60 days to perform an initial review and determine if the application is worth moving to a full review. If the application is incomplete (e.g. required studies were not performed), the FDA will reject it.

Prior to August 11, 2008, there were three possible outcomes of the full application review for accepted submissions:

• an “approval” letter, meaning the drug has met agency standards for safety and efficacy and the drug can be marketed for sale in the United States
• an “approvable” letter, meaning that the drug can probably be approved, provided that some issues are resolved first
• or a “not approvable” letter, meaning that deficiencies are significant enough that it is not clear that approval can be obtained in the future, at least not without substantial additional data

The FDA would issue an “approvable” letter for any number of reasons, from small modifications such as changes to the labeling to large undertakings such as additional clinical trials. The majority of “approvable” drugs eventually go on to win approval. However, in a number of cases, the changes required for approval were too expensive or time consuming for the sponsor, and the project was killed.

With the new policy, there are now two possible outcomes of the full application review:

• an “approval” letter
• or a “complete response” letter, meaning that there are deficiencies in the application such that the application cannot be approved in its present form

The Intent of the New Policy

The FDA’s stated intent behind the change is two-fold:

• Consistency - The FDA has been using “complete response” letters in lieu of “approvable” and “not approvable” letters in the Biologics License Application (BLA) review process for some time. This change brings the NDA review process in line with the BLA process.
• Neutrality - The FDA no longer wishes to imply whether or not a drug is eventually approvable; instead, it only wishes to inform the sponsor of the changes that are required for approval.

The Impact of the New Policy

The most notable difference is the discontinuation of the “not approvable” letter. In the old policy, the “not approvable” letter was effectively a rejection letter - not in all cases, but most. To investors, it was fairly clear that the drug was not going to make it to market, and the stock price of the sponsor company would fall accordingly. The sponsor’s hands became tied as Wall Street had already made the decision as to the future of the drug.

Since the content of a “complete response” letter, as with the old “approvable” letters, is proprietary to the sponsor, it will be more difficult for investors to immediately determine how close a drug is to approval or, conversely, application withdrawal by the sponsor. This is good for pharmaceutical companies. In case of bad news, they will have more time to do damage control before the content of the FDA’s response is known.

However, in the end, the “complete response” letter is not much different than an “approvable” letter. The “complete response” letter still leaves the drug company in limbo as to the future of the product. How much more money must be spent for approval? How much patent time will be lost? Will the product be able to recover the cost and effort necessary for approval?

Since the year 2000, the number of “approvable” letters issued by the FDA has been on a steady rise. The FDA issued 35 “approvable” letters from 2001 to 2004, 13 in 2006, and 23 from Jan 2007 - Sep 2007 (see the “FDA’s Approvable Problem” from Pharmaceutical Executive magazine). There are a number of theories as to why this increase has occurred, but regardless, it is a real phenomenon that is costing sponsors money and killing potentially useful drugs.

In the eyes of the pharmaceutical companies, real change will only come if the FDA reduces the number of “complete response” letters that it sends and increases the number of “approval” letters for first-time submissions. It is doubtful that this will happen anytime soon, but we’ll have to wait and see.

That said, no other exercise gets me into shape more quickly. It gives me reason to hate it even more. I suppose it’s one of life’s cruel ironies that something I hate doing so much could be so good for me. I often wonder to myself (or aloud when I’m running, much to the dismay of passers-by), if there was some way I could get the benefit from my workout with less effort on my part. It is a paradoxical and unrealistic request given everything we know about exercising, but, believe it or not, there may soon be a pill for it.

A California research team doing tests on mice may have identified a method to activate compounds in the body that would increase fat burning ability and dramatically increase endurance, according to Boston.com’s White Coat Notes from Thursday, July 31st. The study, published on the same day in the journal “Cell,” shows that the PPAR-delta master gene, responsible for controlling metabolism and muscle fibers, can be reprogrammed to burn fat and increase exercise endurance using only drugs.

The study obviously has several moral and ethical implications, so much so that in anticipation of the Olympics, scientists in conjunction with the World Anti-Doping Agency have concocted a test for blood and urine that can test for even the tiniest traces of the two substances that make up the drug cocktail. The suspicion is that a lab somewhere may be able to reproduce the chemicals for competitive athletes, giving them an unfair advantage in competition. Any broken record is reason enough for suspicion, as Dara Torres is quickly discovering after she broke a US swimming record recently.

The other downside to the pill is getting the dosage right. According to the study, the month-long trial in the mice would translate to about a three-year regimen in humans. In treating diseases such as obesity, it might be too long a wait.

The process is activated through use of two drugs, AICR and GW1516, the former of which is currently licensed by Schering-Plough to help control bleeding in the human heart. It will probably be some time, however, before clinical trials of the two drugs in tandem can commence, and even longer before scientists understand the implications of changing how muscles function in the body. And I don’t know about you, but the thought of taking one or more pills for the rest of my life to maintain a svelte figure and a higher level of endurance isn’t appealing to me. Perhaps, if proven to be safe, whatever company decides to produce this drug can dangle it as a carrot to Mike Adams, sponsor of the $10,000 health challenge to big pharma.

The fundamental philosophical question is how far we’re willing to push to have something else do the work for us? We’re developing pills to make us younger, pills to make us healthier, pills to put us in better shape. What happened to eating right? Exercising? Scheduling enough time in what seems to be our infinitely busy lives to use the tools that nature gave us rather than looking for the quick fix? As time goes on, it seems more choices are developed by the pharmaceutical industry to circumvent a natural process to give us more time. As we get it, however, we lose sight the one basic principal through which appreciation of that time is developed: our patience.

I think I’ll take that run now.

The kicker is that ROXRO has only six employees. Six employees?!?!  Did I hear that correctly? How does a company with six employees get a drug through Phase III trials and on the doorstep of marketing approval?  Doesn’t it take a small army of people to get a drug to market in the United States of America?  I decided to dig a little deeper and find out how they do it.

ROXRO states that it was one of the first pharmaceutical start-ups built upon the “virtual company” business model.  They operate under a highly experienced senior management team with little to no administrative or professional staff.  Since they have only a small number of employees, there are almost no infrastructure costs.  There’s no need for a HR department, or an IT team or a Finance division.  There’s no need for a company headquarters.  Communication is done through cell phone and email.  Documents are shared via an online file storage site.

OK, but what about the drug development process?  How do they do it with six executives?  First of all, ROXRO is not in the business of trying out thousands of compounds in order to discover a new chemical entity.  They leave that type of work to the big pharmas.  Instead, ROXRO in-licenses promising drug candidates for rapid development in acute medical conditions.  They engage their scientific advisors and a global network of external experts in academia and other small pharmas or biotechs to find and acquire discarded or failed drugs that still have marketing potential.  Then, they figure out how to tweak the product so that it can be successful.

In the case of ROX-888, ROXRO took Ketolorac, a well-known molecule for the treatment of acute pain, investigated why it didn’t work in an oral dosage, and saw the potential for it to be successful in an intranasal form.  Then, they outsourced the drug development, manufacturing and clinical trial programs to external vendors.

Of course, ROXRO needed money to do all of this.  Investors were willing to invest for a number of reasons: ROXRO’s experienced management team and network of experts in the therapeutic area (pain management), their low overhead costs due to their virtual model and the ability to keep their risk profile low by acquiring known - albeit failed - drugs for a more rapid progression through the clinical process.

The final piece of the puzzle is to find a partner (or buyer) in big pharma that has the pocket book and the resources (e.g. employees) to get the drug to market and keep it there.  ROXRO’s plan is to stay small and let the partner handle the resource-intensive operations such as sales & marketing, regulatory affairs, pharmacovigilance, manufacturing, legal, etc.  At present time, ROXRO is seeking U.S. partners for ROX-888.

So, that’s how it’s done.  If you are a scientist with a great drug product idea but think that you do not have the means to get your product to market, perhaps you should think again.  Start up a virtual pharmaceutical company with a few of your experienced and motivated colleagues, get some venture capital, outsource the development and clinical trials, find a big pharma partner, and the next thing you know, you’ve got a product in the game.  Piece of cake, right?

According to the FDA, in order to be considered a “botanical” product, a drug must have the following characteristics:

• A botanical drug product consists of vegetable materials, which may include plant materials, algae, macroscopic fungi, or combinations thereof.
• A botanical drug product may be available as (but not limited to) a solution (e.g., tea), powder, tablet, capsule, elixir, topical, or injection.
• Botanical drug products often have unique features, for example, complex mixtures, lack of a distinct active ingredient, and substantial prior human use. Fermentation products and highly purified or chemically modified botanical substances are not considered botanical drug product. (1)

Headquartered in Jamesburg, NJ, Phytomedics was launched in 1996 to focus on such botanical drug products and has partnered with the Biotech Center at Rutgers University for its research and development, allowing it to function as a private company with access to cutting-edge research facilities while keeping its costs low. Those costs are being covered by several investment firms including Inventages Venture Capital GmbH (life ventures by Nestle), Burrill & Company, Polar Investments Ltd and Biotech M.A.H. Plant Genomic Fund.

The company currently has 2 drugs in development. The first, which has already commenced its Phase III clicnical trial development, is a new, oral drug for treatment of auto-immune diseases. In its Phase II, double-blind clinical trial, PMI-001 was given to 120 patients with moderate to severe rheumatoid arthritis. The results showed significant efficacy of the drug, with rapid pain reduction in as little as 2 weeks and a halt in joint erosion in 6 months. PMI-002 is the second botanical drug under development and shows promise in the treatment of cancerous cells as well as the possible prevention of neurological and opthalamic degenerative disorders.

Other drugs are also in their pipeline, but have not yet received the same focus as their other products (it seems due to lack of funding). These products include:

• A botanical bioactive that acts as a COX-2 inhibitor but with less risk than a Vioxx, Celebrex or other synthetic chemical entity.
• A botanical appetite suppressant that could be leveraged for weight loss, and a counterpart derived from an agricultural waste processing stream that could block fat absorption.
• A plant-derived agent that could be used to limit the impact of aging on muscle cells.

It seems that these drugs, along with the proprietary methodologies the company is using to develop them, could usher in a new wave of drugs that will be prescribed by doctors in the future. As you may know if you’ve read a few of my posts, I’m very interested in keeping an excessive amount of “artifical” stuff out of my body, and the research here shows promise for drugs that may be headed in that direction. I am hopeful that companies like Wellgen and Phytomedics can provide breakthroughs in this area of research and demonstrate the safety and efficacy of these drugs because of their origins as completely natural substances.

However, until an actual product has been released and clinical trials can demonstrate the safety of the product and its interaction in the human body can be better understood, I remain cautious of drugs developed within this emerging field.

Your thoughts?

(1) See “What is a Botanical Drug?“, FDA web site.

One of the persistent challenges of the Pharmaceutical industry has been maintaining the safety and efficacy of drug products in patients over time. In other words, when a patient starts taking the drug, the patient is able to take a lower, safer dose of the product in order to treat the symptoms. However, over time, the patient becomes desensitized or builds tolerance to the drug such that he/she must take higher, less safe doses of the product in order get the desired effect. Eventually, the dosing may reach dangerous levels causing serious, or even fatal, side effects. The crux of the problem is that the pharmaceutical industry does not really have a handle on how target drug-receptors are activated or de-activated in the body in order to achieve the desired result. As a result, desensitization is viewed as an unavoidable side effect.

Last week, I attended the NYC Bio Meetup. One of the presenters was Richard G. Lanzara, President of Enhanced Pharmaceuticals (EP). EP is attempting to combat the problem described above by modulating targeted drug-receptor effects to create new drug combinations which are safer and more effective. EP’s methodology combines an agonist, which triggers a response from the receptor, with an antagonist, which produces no response from the receptor and can block the action of the agonist, in a calculated formulation in order to optimize the drug’s efficacy while curtailing desensitization. EP has shown promising research for improving products used to treat heart failure and asthma. Additionally, EP believes that drugs used to treat Parkinson’s disease, memory loss and other diseases can be enhanced to reduce patient tolerance.

EP does not yet have a website, but the technology was transferred from Bio Balance, and one can obtain more information about their philosophy and technology on the Bio Balance website. EP’s goal is to license the technology to pharmaceutical and biotech companies so that these companies can develop safer, more effective new products and enhance (and potentially extend the patent life of) their existing product lines.

In my limited research (within the first 10 pages of some Google searches), I did not find any competitors for EP nor did I find anyone refuting the ideas and technology put forth by EP/Bio Balance. However, it may be safe to assume that pharmaceutical companies, small and large, have put significant resources toward developing similar/competing technology. On the other hand, this type of technology brings the ethics vs. profit question into light for Big Pharma. While companies have an ethical duty to put forth the safest and most effective products, they may not be able to sell as much of their product if they do. If they are able to create a product that does what it is supposed to do for as long as the patient needs it without a build up of any kind of tolerance, then the patient will never need to increase dosage (such as taking two pills instead of one) and there will be less of a need for more costly variations/extensions of the same product (e.g. extra-strength” variations). Do pharmaceutical companies really want this technology? EP is betting that they do.

EP hopes to start Phase 1 clinical trials of their technology in the near future. Ideally, the clinical trial process will prove that the technology works and provide answers to some of the following questions:

• Over long periods of time, do the combination products retain their efficacy or does desensitization eventually occur? This question may or may not be answered in clinical trials depending on the amount of time it takes to build up tolerance.
• Will the formula work the same for everyone? Different people build up tolerance at different rates. A drug’s efficacy varies from person to person. Will EP’s formula work the same for everyone or will the ratio of agonist-to-antagonist need to change from person to person?
• What new side effects will appear with the agonist/antagonist combination products? While the adverse affects for agonist alone and antagonist alone may be well known, unexpected events may occur when taken together.

EP’s methodology is certainly something to watch in the coming years. If EP can demonstrate that their technology really works and drug companies buy into it, then consumers can look forward to drug products that get the job done safely every time.

She holds an M.S. in Statistics from Rutgers University and a B.A. from Cornell University. She is a member of the American Statistical Association and the New York Area SAS Users Group. Her contributed article and contact information follow.

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For many in businesses that rely on clinical research, the ‘sizzle’ of a headline or claim seems to be enough. But imagine the following scenario:

A prospectus sits on your desk. There is a sentence “The formulation shows a p-value of .023, significance at 95%, at a dose of 10 mg. Sounds good…its statistically significant…move on. But then you get a call six months later. A regulatory reviewer questions the randomization technique. But you thought everything was okay at 95% confidence. They did the statistics.

Statistics are the language for reporting results of efficacy and safety trials. We report significance, confidence and p-values, the probability of an event under certain conditions. These statements make their way into press releases and business documents.

In truth, statisticians play a role before the study is started. They advise on the study design, data collection and implementation. While the study is in progress, they bridge communication between the computer professionals such as programmers and data managers and the medical professionals such as clinical investigators and research associates.

In the jargon of the industry, the research on human subjects is referred to as Phase 1 through Phase 4 clinical while other activities such as drug discovery, manufacturing and toxicology get lumped into “non-clinical”. Clinical statisticians do work in a structure of tables, listings and graphs that adheres to the requirements of the FDA and various other national and international organizations. The roles vary for non-clinical statisticians. There is more interest in applications of statistics in early stage research and manufacturing processes.

One can find various definitions of the word ‘statistics,’ including the vernacular usage as any display of numbers. The American Statistical Association in its career section website (www.amstat.org/careers) answers the question “What is statistics?” as follows–Statistics is the scientific application of mathematical principles to the collection, analysis, and presentation of numerical data. Statisticians talk in the language of science-observation, estimation, hypotheses, generalization and modeling. Unlike other approaches to data analysis that aim only for a mathematical optimization, statistical analysis concerns itself with the scientific context of the data collection such as the measurement ranges and precision of lab equipment. It is not black-box computation.

In the early 20th century a mathematical framework for statistics emerged built on the backbone of probability theory, an older branch of mathematics. The expansion of this mathematical framework continues in universities around the world. While clinical research sometimes uses new techniques, it relies on basic ideas like distributions of averages and randomization. Randomization is a plan for treatment assignment that is independent of human choice. We know the probability that a subject is placed in a treatment group. This assignment lets the researcher use probability-based statistics to assess the effect of a treatment and whether it is just a result of ‘chance.’

As a professional statistician, most people find what I do mysterious. They remember a dreaded required course. If older they think of grayish books with grids and curves. If younger they think of the horrible software they were forced to use. Fortunately these classes, the books and the software are now a lot more applicable, even fun.

But you don’t have to take a new-fangled level 200 class to bring make clinical statistics more relevant. A good start is thinking about the numbers that express the result. This will make your questions more effective. A desired clinical change can be expressed as a change in a decimal number, a count, or a percent. A ‘20% drop’ can explain going from ‘200 to 160′ or ‘15 to 12′. This is where the ‘scientific context’ becomes important. The expression of a clinical result is the end-product of the clinical practices, the regulatory guidelines, previous company studies, and the judgment of the current statistician, and perhaps a previous statistician.

My ending comment is stay aware. A short phrase in a business or legal document is a small blip in the thousands of pages in a clinical trial submission. The minds of regulatory reviewers are at once specialized and focused but tuned into current trends. Clinical statistics can become pivotal in the approval process.

Georgette Asherman
Applied Statistician
Direct Effects, LLC.
www.directeffects.net
201 673-4301

First on the list is Advair, an asthma medication. He cites an analysis in 2006 of 19 trials that suggested that regular use of LABAs (long-acting beta-agonists) can increase the severity of an asthma attack, even to the point of death. Advair (also known by its generic name salmeterol), is the most popularly prescribed of the LABAs and could contribute to as many as 5,000 asthma-related deaths each year in the US. It lead to the FDA labeling the drug with a black-box warning, its most severe.

The next two on his list are probably familiar to readers of this blog: Avandia and Celebrex. I’ve written at length about the two, and their challenge to stay on the market in spite of being labeled with their own black-box warning by the FDA (search for “Avandia” or “Celebrex” and you’ll find multiple posts on this site). Avandia was removed from the market at one point because it was linked to cardiovascular disease in some patients. Celebrex, like its other CO2-inhibitor cousins Bextra and Vioxx, was also associated with cardiovascular risk.

The powerful antibiotic Ketek is next on his list, which is prescribed to fight bacteria in the lungs and sinuses, but has been liked to heart-rhythm problems, severe liver side effects and poor interaction with other medicines one may be taking. In February 2007, the FDA formally limited its use only in the treatment of pneumonia.

Heartburn medications Prilosec and Nexium were next, and again, there is an investigation that’s been done by the FDA into a suspected link between these medications and heart attacks. Based on that investigation, the FDA said there isn’t a likely connection, which Lord interprets as meaning “the scientific jury is still out,” but I would hardly put this on a list of “medicines to avoid” if no conclusive link has yet been made even after a study has been completed. He goes on to indicate that the medicines are perhaps too effective anyway, because that same sensation of burning in your chest will kill incoming bacteria and germs that could lead to pneumonia.

Visine was next, a surprise when I first read it until I realized he was talking about the original formula. The original formual “gets the red out” of your eyes by constricting the blood vessels causing the redness, and not actually addressing the cause (such as dryness or allergies). Continual use can perpetuate and even worsen the problem. When my eyes get dry, I occasionally use Visine Pure Tears, which do not contain the active ingredient tetrahydrozoline, which causes the constriction seen with use of Visine Original. (I was waiting for the link to heart attacks, but it never came for Visine.)

The final drug on the list was Pseudoephedrine, a decongestant that could cause problems for people with heart disease or hypertension because it not only constricts the blood vessels in your nose and sinuses, but could also raise blood pressure and heart rate, a definite problem if you have a history of heart problems.

For each drug, Lord does an excellent job of giving alternatives to these medications, but I felt like his profile for each of these was a bit alarmist in nature. Are these really 8 drugs that doctors would never take? So many of them seemed to be linked to heart problems, but do they actually cause heart problems or exacerbate existing conditions? What’s his basis for claiming that most doctors wouldn’t pick up the Physicians’ Desk Reference to check for the serious side effects that these drugs may cause? Or, for that matter, not warn their patients of the potentially fatal side effects and risk a serious malpractice suit?

I would have liked to see some kind of indication of a study (e.g., ‘x’ number of doctors were surveyed for this article and ‘y’ picked these 8 drugs as things they would never take) or some other insight as to why he picked these particular drugs. And what does he say to people who are already on these drugs and find they’re helping? In my post, “Heartburn Relief,” there’s evidence that the alternatives he suggests for Prilosec and Nexium aren’t as effective at treating heartburn. And drugs like Celebrex succeeds in spite of its black box warning because, simply, it works for it patient base who should be well aware of the dangers of their medications if their doctors are doing their job in disseminating information appropriately (I explored this more in “Succeeding in Spite of a Black Box“). Is it realistic to think that prescriptions for these medications are haphazardly given, or are the patients taking them better educated than we think?

I’d love to see more of Lord’s work into this area, perhaps a deeper profile into the doctors that *do* prescribe these medications (or suggest them, in the case of over-the-counter drugs) and why they do so. For that matter, I’d be more interested in taking a closer look at over-the-counter drugs that could be dangerous if taken in high doses, or problematic at least if they’re taken at the recommended doses. Claritin, for example, is a godsend for me during allergy season, but I’m always concerned when a drug makes a jump from prescription-only to over-the-counter. What about Zyrtec?

Lord’s article makes for interesting reading. But there is definitely more research that would need to be done before I would be convinced these are the 8 drugs doctors would not prescribe, and certainly a wealth of other information out there from which people would probably benefit. I hope he, or another writer, will explore the possibilities soon.

What do you think?

Nutrigenomics, according to the Wellgen web site, is the study of how foods and their bioactives, components we more commonly know as vitamins and minerals, interact with genes in the human body to affect health. The concept is that the more we know about this interaction, the better able we’ll be to create customized regiments in human eating habits to promote optimal health based on gene makeup. The first application of this concept has been developed in their first product, WG0401, which is a patented extraction process that takes the beneficial phytonutrients (nutrients of plant origin) found in black tea and applies them to the human body to reduce inflammation in the muscles and provide other benefits to patients. Their second, still unreleased product involves pairing weight management with the phytonutrients found in citrus fruits.(1)

I am admittedly curious about this new product and its implications for the Pharmaceutical and Biotechnology industries. I mean, could WellGen be considered a Pharmaceutical if its products are chemically identical to the same substances we find in natural foods? And, what differentiates these products from the supplements we find in health food stores? It reminded me of the product that Sirtris Pharmaceuticals is developing based on the key ingredient in wine, resveratrol, that has been linked to longevity and endurance in lab tests on mice (see my original article here). How will these products be regulated by the FDA — will it require the development of a new set of rules to review unique products coming on the market?

By all means, I’m interested in what this kind of science could mean for the future of human health — and whether this research will lead to more preventative medicines with less risk for the human body. Still, we’re altering the quantities that we would normally consume just by the food we’re eating; does that carry with it some risks? Is too much of a good thing wonderful, as Mae West may have quipped, or do we tread softly as we move forward?

In an article by Kitta MacPherson of the Star-Ledger, “Genetics Key to New Preventative Medicine,” it seems that CEO Dr. Mullinix doesn’t think so. Scientists at her company took advantage of

20 years of fabulous molecular biology work which had identified 15 genes, including interleukins and cytokines, involved in causing the inflammation makes muscles and joints sore. In test tubes and, later, in controlled tests on mice and then people, scientists found the substance inhibited inflammation. (2)

Given the seemingly natural path this company is taking, I’d be curious to know what Mike Adams thinks about their products (if you don’t recall, he’s the nutrition expert who issued a $10,000 challenge to BigPharma that I wrote about last week). For that matter, any health expert’s opinion might be interesting to hear. As a hopefully viable replacement for COX2 inhibitors, I would certainly feel more comfortable taking a supplement derived from tea leaves for aching bones instead of a pill that, however remote, has been linked to heart attacks.

Then again, you may remember that “Dieter’s Green Tea” mentioned in my “Supplemental Health” post was the alleged cause of death for June Grell, an otherwise picture of health, at 37 years old.

Maybe, even with products derived from naturally occurring chemicals, I’ll stick to my current regimen, NUN: Nothing Unless Needed.

What do you think?

(1) See “Products” page of the WellGen web site.

(2) See “Genetics Key to New Preventative Medicine,” Kitta MacPherson, Star-Ledger, July 16, 2007 (as republished on the WellGen web site).

The premise of the challenge is that Mike Adams wants to prove that taking medications, on a preventative basis, really does not lead to optimal health. In theory, this is a great challenge to Pharmaceuticals, though I don’t think he will get much response from the major players in the industry. One of the innate problems in his campaign is the qualification that his challenger must be taking 10 different types of drugs, and must have been doing so on a preventative basis for a year. The list of the 10 types of drugs is as follows:

• COX-2 inhibitor (anti-inflammatory)
• Blood thinner drug (like Coumadin)
• Blood pressure drug (like Toprol)
• Statin drug (anti-cholesterol)
• SSRI drug (antidepressant)
• Sleep drug (like Ambien)
• Hypertension drug (like Norvasc)
• Antibiotic (like Amoxicillin)

Firstly, I doubt that there are many people under 65 who would be taking such a cocktail of drugs on a preventative basis, and given that Big Pharma is unlikely to know about any of its patients unless there is an actual adverse event reported, I’m not sure that they would even know where to find someone with such a qualification.

Secondly, I think Adams’ list sets up a Big Pharmaceutical company for failure already, because some of the drugs he lists are known to interact in the body in such a way that most doctors probably wouldn’t prescribe the two medicines together. In fact, in the article “Bad Combinations” published by Harvard Medical International in April 2004, we see that some of what Adams lists are known to interact poorly with one another and it would thus be impossible to find someone taking two. For example, Warfarin (AKA Coumadin) thins the blood by binding to albumin in the blood stream. Some antibiotics bind to the same protein, so if the two drugs are combined they could cause the amount of active and unbound Warfarin to soar in the body and with it the risk of uncontrollable bleeding. Another example is that ACE Inhibitors, which treat hypertension, would likely not be prescribed with COX-2 inhibitors like Celebrex or Bextra because the latter essentially negates the efficacy of the former.

What would make Adams’ challenge more interesting to me is if he just picked 1 or 2 drugs — any 2 on his list — and used that as its basis. Given the items he lists, I don’t think anybody taking even one of these drugs would be able to meet a physical fitness challenge. I also think Mike should amend his challenge to state that, given his background in personal health, he would help the person with a plan to eat right, exercise and get him or herself into better shape (enough that he/she no longer needs the drugs) and retake the challenge in 1 year. Make the participant compete against his/her own performance from the previous year. Strengthen the proof that your philosophy works by helping someone out who really needs it.

Let’s be clear: In many respects, I do not disagree with Mike. I think there are far too many doctors who have been given incentive by the pharmaceutical industry to pull out their prescription pad and give drugs to mask symptoms that won’t go away without some serious life changes. But I also believe that life is about balance, and the health that Mike has achieved may not be something that’s possible for all people — genetics, availability of health food choices, expense, they all play a partial role in the decisions that we make, and taking the time out of the day to mix a “superfoods” drink might not be possible for every person.

Take me, for example; I avoid taking drugs whenever possible, I eat lots of fruits and vegetables, I exercise, and my current state of health reflects that. My wife does the same, and we’re trying to pass that philosophy on to our son. But I’m not going to avoid taking an antibiotic if I have a bacterial infection. And sometimes a headache is just a headache and I’m going to take ibuprofen to get some relief. And given that my line of work is not focused on personal health, I cannot realistically spend my day preparing the kinds of foods I’d need to eat to be on the same level of fitness as Mike claims to be.

Not to mention, what do you tell a schizophrenic who depends on his/her medications to maintain a clear head? Or the countless people infected with HIV who have lived years beyond their original prognosis? While I agree that the Big Pharmas, like any business, are out to make money, we can’t minimize the impact they’ve had on people whose very lives depend on the drugs they’re taking.

So yes, let’s target the “preventative” medications, but make the challenge a little more serious. If one participant can see that a healthy lifestyle will give more benefits than any one pill, then the reward would be far greater than just embarrassing a person who has been led to believe his/her current drug cocktail is medically necessary.

What do you think?

But this week, we return to blogging with another entry into the virtual world of Second Life. I was excited last Wednesday evening, June 11th, to be able to attend a talk hosted by Simon Bignell, a lecturer at the University of Derby in the United Kingdom. Using his Second Life alter ego, Milton Broome, Simon gave us about an hour of his time as he told us about the research that’s being done in virtual worlds on Autism spectrum disorder and Asperger’s (to keep tabs on what Milton is up to, check out his web site).

This was my first experience using the voice features of Second Life, and I must say I was impressed by the fluidity of the lecture given that I could now hear the virtual presenter speak as opposed to just listening to text being typed on a keyboard before a paragraph appeared on my screen (to read more about the first lecture I attended, which was not voice enabled, click here). There were some technical difficulties to start (objects creating the ever-present sound of waves in the background, for example), but once the lecture began I thought things went very well; it was clear to me that Simon/Milton had done this before.

The objective of Simon’s project is to determine if Second Life, and virtual worlds like it, can be used as a medium to help develop the social and communication skills of those people who might be suffering with some form of Autism. Firstly, in spite of promoting its voice capabilities more and more, the ability to have typewritten conversations in Second life is really an advantage to people in this group; because of their difficulty at quickly and correctly interpreting social situations, the autism community has embraced this medium because it effectively slows down the social interaction to a point where they can keep pace and learn the dynamic skills necessary to react appropriately. Simon emphasized this by pointing out that the average colloquial conversation occurs at 150 to 200 words per minute; the typewritten conversation, at best, occurs at 15 to 20 words per minute, 10 times slower than a spoken conversation. Therefore, in spite of all the advances made with voice communications in Second Life, and the ability to have a real lecture in a virtual world, the autistic community might not be ready to embrace this kind of advancement as readily as some of their non-suffering counterparts.

In fact, most of the work Simon is currently doing revolves around understanding the needs and developing programs to assist the growing community of people living with Autism in Second Life and he’s clearly not alone. You may recall my blog entry in January, “Bridging Solitary to Social Via Virtual Reality,” where I wrote about Center for Brain Health at the University of Texas at Dallas, who developed a virtual town in Second Life as a kind of treatment area for Autsim. I’ve posed the question before: is there a possibility that a Second Life could serve as a therapeutic instrument for a First Life?

A critical component of that is better understanding the condition you’re trying to treat. To that end, I was pretty interested to hear that Simon is working on an “Autism Simulator,” similar in scope to the Schizophrenia simulator I visited very early in the existence of this blog (see: “Schizophrenia with a Technology Twist“). With it, Simon hopes to reproduce some of the sensations someone living with Autism might experience, including alterations in light, noise, touch, and even obsessions and comorbidity. Ultimately, he hopes to use this project as a platform for collaboration among the many groups in Second Life who strive to understand more about this condition and ways to treat it.

There is no doubt in my mind that Second Life and people like Simon Bignell provide novel ways to investigate and understand the challenges associated with social conditions such as Asperger’s and Autism. While I still feel today, as I did a year ago, that things are probably not yet where they need to be in order to bring the technology to the masses, I do feel that there is progress. The greatest difficulty, perhaps, is conveying the idea that places like Second Life are more than just a platform for gaming; they are worlds that can be shaped entirely by the power of human imagination — that is, of course, if the technology can keep up.

What do you think?