Monday, December 10, 2012

The Fog.

There is a thick blanket of fog covering the Triangle area of North Carolina this morning.  Its murky depths and light refusing aspect are a mirror on my soul as I seek to apply Evan’s lessons to living today.  The candle lit last night as part of the worldwide remembrance of children felled by cancer is long extinguished, and like the flame not flickering so our own hearts falter.  And against this backdrop of potentially overwhelming depression I awake to this heavy fog that seems to foreshadow the lack of vision and leadership that has socked in the political leadership in Washington and Raleigh alike.

Fog forms when cold air and hot air come together in a humid environment.  The greater the temperature difference coupled with higher humidity results in the thickest fog. In political arenas, the analogy would reference the distance between the central characters in a debate and the humidity would be equated to the size of the money pile being discussed. The future is always a little murky when two sides start from different points of view, and the more difficult for the sunlight of consensus to breakthrough.  It is I suppose a case of the right hand not knowing what the left hand is doing.

Of course consensus is gained by communication, the process of give and take, often involving taking the time to listen twice as much as speaking.  This is of course something that is happening less and less in the seats of government all over the world. And so the entire world is faced with asking the underlying question that is like the 400lb gorilla in the room: What is the role of government in our lives?

This is not a call to anarchy, although anarchy is one of the possible outcomes of a failure to govern.  Nor is it to advocate for anything at the other end of the political spectrum such as dictatorships whether benevolent or not. It really is as fundamental as to ask the question: What is government supposed to do?

Is government to protect us? Is it to keep us safe from each other? Is it to ensure that we are all happy?  If these questions can be answered, they should be.  And the answers should lead to consensus of governmental function.  The challenge to successful communications is our own sense of entitlement. But the essence of government is to make laws, enforce the laws and adjudicate the laws; with an understanding that every law written is some form of ‘rights’ entitlement. 

We are entitled to the defense of the country and the upholding of the constitution upon which it was created.  We are entitled to be able to live life seeking out the opportunities that document says we are afforded: life, liberty and the pursuit of happiness.  Along the way these constitutional rights have been codified by the making of laws.  We have laws which prohibit murder, kidnapping and robbery.  We have built roads to facilitate transportation of goods and people which enables commerce.  And we have passed laws to ensure that our food and medicines are safe to use in light of cost cutting measures that maximized profits.

In an effort to ensure that a reasonable profit is made from ingenuity and investment, patent laws grant competition free production for a limited amount of time.  And here in lies the catch 22 of laws made within a republic where the core values of individual rights protection clashes with the best interests of the civil community.  So in summation legislative sections of governments make laws to enshrine rights, the executive branch is charged with enforcing those laws (which due to the size and scope of the laws entails an ever-growing bureaucracy) and the judicial branch is required to adjudicate the executive implementation of the law whether by individual v individual, society v individual or any section or group held within that spectrum.  The gist here is that the right hand and the left hand are similar in their desire for protection but also often wants to gain the upper hand.

For the sake of this essay I shall use a very crude analysis of the FDA as a case study for the points raised above.  The Food and Drug Administration (FDA) is a bureaucratic entity tasked with the executive administration of the laws designed for the protection of our health and welfare in relation to certain foods, not all foods or ingested products.  In the Federal Hierarchy it reports to the Department of Health and Human Services (DHHS).  At this hierarchical level of reporting to DHHS, FDA is adjacent to the National Institute of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resource and Service Administration (HRSA), Center for Disease Control (CDC) and the Health Care Financing Administration (HCFA) among others.

So under the DHHS umbrella the competing mouths to be heard and fed include Medicare, Medicaid, Health Care Reform, Infectious disease containment, substance abuse, mental health along with the oversight of certain food additives, medications and medical devices.  As un- or underinsured individuals fight for government coverage for the medical services available in one hand, on the other is an agency tasked to approving medicines for usage by the general population that are subjected to regulatory oversight that is used to ensure efficacy.  These same protective measures drive the cost of the medicines up while the time to conform cuts into market time at profitability. 

There is a complication in the right hand left hand analogy at this point.  Drug companies are owned by individuals and the profit motive is driven by the money managers for those individuals; on the other side of the equation are the people who stand to benefit from the medicines who the FDA attempts to protect.
Let’s take a look at one specific drug that was rushed to market in the late 1950’s Thalidomide.  It was intended as a sleeping pill, but had tremendous positive results in an off label application of suppressing morning sickness.  Off label use of medications by doctors is a common practice where the ‘side’ effects  of medicines are helpful to patients in certain situations.

And through careful monitoring patients are able to benefit from this polyeffective processes.  (Ibuprofen, Aspirin and Aleve are all NSAIDS and they have a variety of different mechanisms of action that among other things reduce pain, inflammation and fevers to varying degrees) As medi cations continue a review process, the FDA can move to allow doctor only prescription to an over-the-counter status.  But sometimes the pressures of success combined with inadequate trials result in medications reaching the market before they have been adequately evaluated.

In the case of Thalidomide, the teratogenic (a term used to describe the genetic disruption that a fetus may undergo without necessarily resulting in a miscarriage) effects of the medication resulted in hundreds of birth defects, because the drug was so widely prescribed off label without appropriate research.  It was only in the market for 4 years, but became the poster child for future testing prior to market approval.  It has recently been reintroduced to the research field as a possible tool against certain autoimmune diseases and cancers. 
But one of the most shocking points was brought to light in 2000 when it was determined that only one of the variants of Thalidomide was teratogenic, the S version or left handed molecule was able to insert itself into the purine groove of the fetal DNA causing DNA replication errors. 

It is now time for a little background on pharmaceuticals. Drugs are made of strings of carbon skeletons (organic chemistry), and as they are formed there appears no difference in the physical properties of the drug where a 50-50 mixture of a drugs right and left hand variants.  The determining factor is called a chiral center and results in either an R or S variant.  Typically there are no steps to ensure just one or the other form and the resulting blend is called a racemic mixture. 

Racemic mixtures only exist in synthetic organic molecules.  Nature only produces S or left handed variants.  It is why DNA only twists one way.  It also creates lock and key mechanism’s with the synthetic variants of a racemic mixture of a drug.  Unless there is an overriding need to isolate just one variant over another, the economics of production dictate a racemic mixture. 
The second shocking point was that Thalidomide was never licensed for use in the United States; however, the distribution of millions of pills to US doctors was facilitated as part of a ‘widespread’ unreported study by the manufacturer.  But the fallout has been a tightening of regulations and less profitable time in the US market before patent protection runs out.

The production of a drug requires immense amounts of effort and resources, but once it has been initially synthesized, a drug company will seek patent protection and begin the process of clinical trials to bring a drug to market. In 1957, Thalidomide enjoyed less than a year of clinical trials and was afforded 20 years of patent protection.

Today, the safest drugs still undergo at least an 8 year wait to approved licensing and release for use.  While the costs have risen dramatically, the profits have potentially been driven down, all while the pressures on performance are driven by a board room stocked with people like you and me who are looking to maximized our retirement holdings.

But before you feel too guilty, there is also an unsavory leadership trend and a generic reality to address.  Many in the upper echelons of the major pharma manufacturers have sought to extend their profits by buying off the generic manufacturers asking them to hold off on generic production for a couple of years.  The costs of the drug to recipients is a part of the profit line pricing of any drug.  Given X costs to bring a drug to market, an expected use by Y patients, and a minimum required profit of Z, a price is set to offset R&D costs – perhaps of several drugs since the success to failure rate can be quite high. So big pharma makes more money by buying off generic manufacturers – this is a practice now under investigation by the Federal government, but the practice has been going on for years.

And then there is the status of generic drugs vs name brand.  Remember the whole RS deal with the chiral centers and the same physical characteristics of organic chemistry above.  This is the definition of a generic drug according to the FDA:
A generic drug is identical -- or bioequivalent -- to a brand name drug in dosage form, safety, strength, route of administration, quality, performance characteristics and intended use. Although generic drugs are chemically identical to their branded counterparts, they are typically sold at substantial discounts from the branded price. According to the Congressional Budget Office, generic drugs save consumers an estimated $8 to $10 billion a year at retail pharmacies. Even more billions are saved when hospitals use generics.

But what if the original manufacturer has isolated a production technique for R or S variants in greater or lesser quanity, and what if the process uses different ingredients to reach a similar characteristic.  For some people this will not matter, but for for some others this might spell the difference between health and illness or between life and death.

I am sorry for winding a chemistry lesson into a civics lesson into pharmaceutical reform, but the intertwining of all these elements is found in the need to have a mutual respect for one another that we cannot codify into laws as much as we should seek to live a more compassionate life toward each other.  The best example I have ever seen of this principle in action is the Rotary International Four-Way Test

The Four-Way Test
The test, which has been translated into more than 100 languages, asks the following questions:
Of the things we think, say or do
1.     Is it the TRUTH?
2.     Is it FAIR to all concerned?
3.     Will it build GOODWILL and BETTER FRIENDSHIPS?
4.     Will it be BENEFICIAL to all concerned?

I am unable to put a life statement into better words.  Now if the politicians who purport to lead us would start to try and live these ideals out and seek to not uplift their constituents with bribes and pride but with education and relationships, we might find ourselves walking in fields of barley instead of toward a cliff.
As you each engage the variety of ideas here we might start a dialogue on one or more of the rich veins of interest and together we might find common ground and common purpose.   

I know this meal is the size of an elephant, but if you put your fork in your left hand and knife in the right, together we might polish this off with a few of our friends. 

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