Having It Both Ways: State Sanctioned Medical Marijuana vs. FDA Oversight?

---Terri Bernacchi, PharmD, MBA,  President, Cambria Health Advisory Professionals

As someone who got a BS in Pharmacy in 1979, an MBA in 1990 and a PharmD in 2008, I have seen a few things change over 35+ years in regards to the manufacture, regulation and marketing of drugs in the United States.  Some things are now rather “topsy-turvy” compared with the reality of my early professional years.

I’ve worked as a hospital and retail pharmacist, for a major pharmaceutical manufacturer, a large health plan and a hospital system.  Last, I owned a business forcing me to apply theory to practice:  I had to make payroll.  These experiences left me with a certain “steeped in reality” perspective that goes beyond things I read in textbooks or heard from my professors.  Life, as it unfolded, has also progressed my political leanings from naïve liberal to conservative to almost libertarian as I witnessed and felt the result of regulatory misadventures and their unforeseen consequences on the “little people”.  Bureaucracies may mean well but they are never "efficient". 

For example, when I went to Pharmacy School in 1979, I learned the following in my Jurisprudence courses about the bureaucracy we know as the Federal Food & Drug Administration: 
 

• The FDA is there to protect the citizenry from fake, dangerous or adulterated food and drugs.  The creation of the FDA was precipitated as part of the 1906 Food & Drug Act after snake oil salesman sold their secret tonics to treat everything from fatigue to menopause to heart diseases or cancer. These tonics often contained dangerous drugs like morphine, cocaine, or potentially toxic substances like arsenic or digitalis in variable doses.  Food contamination and handling was as important as the drug purity and was brought to light in Upton Sinclair's novel, The Jungle. 
• Drugs marketed in the late 1970s were typically either “over the counter” or legend (available by prescription only).  All of them, with the exception of a "grandfathered" few, were under the direct scrutiny of the FDA.  Some products, like heroin or LSD, were so highly regulated that they could not be legally manufactured or sold in the United States at all; these were deemed to offer little medical value relative to the detrimental effects.  Others, like food supplements and “natural” products were pretty much unregulated---much like they are today.  You can find these products sold with wild and unsubstantiated claims on the internet, in the back of tabloid magazines, or in the “nutritional supplement” aisles of health and drug stores.   
• We learned the history of thalidomide and the need to test drugs for effects on the developing fetus.  Indeed, Dr. Frances Kelsey was something close to a saint for her work in preventing the US FDA’s approval of the sedative thalidomide.  England experienced thousands of limb malformations from the drug’s use in pregnant women; the US largely avoided this disaster thanks to Dr. Kelsey.   
• The FDA was presented to us students, singularly, as a heroic regulator, necessary to a safe and effective drug supply, advocating for the patient at every turn.  The rules of the FDA, we were told, are applied to all 50 states; as it is a Federal agency, its rules trumps those of the states.  Certainly, the Controlled Substances Act (enforced by the Drug Enforcement Agency) applies as well to each of the states.
• I thought, briefly, that it might be great to work for the FDA or the CDC.  They are clearly doing interesting and important work. I tend to believe that there is a role for some governmental oversight of things that are sold for ingestion of the people.
• While its mission is presented in noble and lofty terms about protecting the public and speeding innovations (see http://www.fda.gov/aboutfda/whatwedo/), the FDA has often been criticized (sometimes to the point of vilification) for delays in the approval of drugs that are openly available in other countries.  Over the course of the past century, the agency itself has grown and the mission has been expanded.
  
  It is certainly more expensive to bring a drug to market than it was in 1960, but back then the government was not responsible for paying for it.  Now, under Medicare, Medicaid, federal employee insurance, and the ACA, the Government is a key payer.  The FDA has a 2014 budget in excess of $4 billion and employs more than 9,300 federal employees.  The costs of the FDA are significant, whatever the value it brings.
In today's environment, Pharma and device companies must work through an onerous product approval and regulatory process that adds millions (often hundreds of millions) of dollars to the cost of developing a new drug or device.  Not surprisingly, these costs are added to the cost of insurance coverage and are ultimately born by the consumer and the taxpayer.  In addition, the federal government is applying ever more user fees, taxes, and discounts to the pharmaceutical and device manufacturers which pass along these costs as well.  Disproportionate cost shifting to the private sector remains the primary impact of all of the financial burden.

For my part, I wonder about the effectiveness of FDA security measures protecting the US public from the importation of inferior or even counterfeit drugs.  The FDA cannot be everywhere and there is a lot of money chasing prescription drugs which breeds bad guys seeking to rip somebody off.

So, after all these years, I am left somewhat bemused as I look at what is happening now regarding marijuana!!

Where is the FDA and DEA on these issues? There are a couple of points that are particularly peculiar: 

Apparent Reversal of Focus Away from Pot and Towards Sugar.  For the past couple of years, state, local, and federal regulatory initiatives around smoking cigarettes, drinking soda pop or eating foods we might otherwise choose are becoming more burdensome at the very time that the FDA and DEA seem to be “giving up” on their efforts to control the sale and distribution of marijuana, ignoring relaxation of rules at the state level.  So, we are tightening the rules on cigarettes and soda pop and loosening the rules on what has always been called, the “gateway” drug. 

For example, in 2014, it is now more time-consuming to buy pseudoephedrine at the pharmacy than it is for someone to score some pot, completely free of criminal consequences.  We seem to be promoting the use of marijuana and restricting the use of decongestants; we won’t mess too much with tobacco (because of the tax revenues), so we are now taxing / restricting sugar consumption. Duh.

Certainly, the costs (police, prisons, court dockets, and medical costs) of enforcing pot laws to any state versus the revenues associated with taxing its use make the financial benefit of legalizing pot apparent to everyone.  These new measures save costs and increase revenue.  Duh, again.

However, the recent federal response, it seems, is to pick and choose which laws to ignore and which ones to enforce.  This seems like “lawlessness” to me. But this attitude would be surprising coming from the DEA or FDA, as I have known them.  I could be wrong; perhaps I missed their press releases to the contrary.

Safety Concerns Seem to Be Arbitrary.  When one inquires about the justification for the War on Drugs, the basis for rules around manufacture and distribution, and the inspections of pharmaceutical factories, “public safety” is always the key reason for the regulations.  We all know the safety concerns around cigarettes, alcohol consumption, and maternal drug use.  But are we ready to ignore the dangers of marijuana on children, pregnant women and drivers?  What about potential drug or disease interactions?

Both marijuana and tobacco, when smoked, deposit the same junk into the lungs.  The combustion of organic materials contains more than just the active ingredients; the smoke contains tars, detrimental carbon monoxide, and carcinogens, and potential molds or insecticides.  It also contains inconsistent amounts of the active ingredients. The FDA I am familiar with would want to assure a consistent product for the safety of the public, right?  Wrong?

If pregnant women should avoid alcohol and tobacco products, shouldn’t they also avoid pot?  Where is the labeling requirement to assure that they are informed of this?  Do labeling warnings even work as a deterrent?

Product Integrity.  The FDA expends tremendous effort and countless millions to assure that “Good Manufacturing Practices” (GMP) are used by certified manufacturers to keep the drug supply safe.  Not the least of the reasons for applying GMPs to these factories is to assure that dosages of active ingredients and formulations are consistent from one lot to the next and from one manufacturer to the next.   Where is the assurance about the variability of an organic product that is not lot-tested or subject to GMP?  How do we know that a given batch of pot does not contain molds or other toxins? Who oversees the production processes to protect the public?

What will happen when someone using medical marijuana has a bad outcome?  Will it be reported? Will the person be able to sue the producer, the supplier, or the state that permitted it? These are the same kind of lawsuits brought by plaintiffs to pharmaceutical companies every day. 

Is it ONLY about money? I am concluding that some of this is just hypocritical and is being permitted in order to permit the states to fill their coffers with marijuana-related tax money. Don’t get me wrong: I am not saying that we should infringe on the right of someone to do whatever he or she wants to do with his or her own life. That includes, I think, using marijuana, even growing their own, even buying an unregulated product.  I'm not even against the state collecting taxes to cover the new challenges this drug use will bring them.  

However, I think that if you are going to enforce rules for drug or device products, you should have a policy that is rational for all products.  Manufacturers should be held accountable for the integrity and purity of a drug or device product; even pot manufacturers.  Buyers should be aware that there are down-sides that are often not evident and they are using at their own risk.  But does the mission of the FDA stop at State Pot Distributors? Will legalized Cocaine or Heroin be next?  If not, why not?

State versus Federal Scoff Laws.   Both marijuana and tobacco fall under various local, state or federal laws governing their production and sale (including taxes and age limitations), but the 2014 rules for Colorado are particularly interesting because it is still against FEDERAL law but permissible (at a private residence with the permission  of the home owner as long as no one else can smell it.)  The patchwork of laws and regulations are likely to grow in number, creating confusion for the user and the authorities alike, especially near state borders. See the latest on Colorado rules for a recent example:   http://www.denverpost.com/marijuana/ci_24823785/colorado-marijuana-guide-64-answers-commonly-asked-questions

Is there a rational compromise?  As an embryonic libertarian, I would say the answer to this depends on whether or not you believe there should even be an FDA. As I stated earlier, I think I can make the case for an efficient "small government" agency to oversee the safety and purity of marketed products.

Should there be a role for the government (funded by taxpayers) to regulate the sale and production of various drugs, including marijuana, in order to protect the people?  Or should people be free to ingest/inject/apply anything that is sold on the street? 

The next question is whether or not the regulation and enforcement should be at a local, state, or federal level.  That opens up a HUGE discussion, well beyond the scope of this post. 

In the meantime, you can smoke Pot if you want to, and I think I am even up to defending your right to smoke it and be unmolested by the government.  However, I don't know how it will impact your "employability". For example, if I have to make payroll, I would rather employ the attentive worker whose brain is free of cannabinoids than the worker who engages, even occasionally, in the use of pot if it objectively reduces work performance.  THC is a chemical that alters the conscious brain and has been shown to be detrimental over time.  As an employer, I need the maximal output of that brain.  So in a purely libertarian world, it would be my choice to discriminate against pot users.

Will Colorado apply laws that could infringe upon the right of the employer to say “no” to potheads?  We are living in INTERESTING times.  Can’t wait to see what happens next!

Terri is a Senior Partner at Valiant Health, LLC, and founder of Cambria Health Advisory Professionals.  The thoughts put forth on these postings are not necessarily reflective of the views of her employers, clients nor other Valiant Health colleagues. Terri has had a varied career in health related settings including: 9 years in a clinical hospital pharmacy setting, 3 years as a pharmaceutical sales rep serving government, wholesaler, managed markets and traditional physician sales, 3 years working for the executive team of an integrated health system working with physician practices, 4 years as the director of pharmacy for a large BCBS plan, 12 years of experience as founder and primary servant of a health technology company which was sold to IMS Health in late 2007.  She has both a BS and a PharmD in Pharmacy and an MBA 

   

Advocating for the Individual in a World of RWE and CER

---Terri Bernacchi, PharmD, MBA,  Senior Partner, Valiant Health

The history of the Federal Food and Drug Administration is a fascinating story that balances the federal government’s actions in support of keeping the citizenry safe from snake oil salesman selling poison and the food and drug supply “pure” against the capitalist that drives innovation in the area of health care improvement.  The story of the FDA is one that will never be over but unless someone actually understands what has happened in the past and WHY certain official positions have been imposed, the beneficial nuances can be completely lost in the jargon.

For example, the FDA was charged with assuring that a manufacturer wishing to market a health, food, or cosmetic product in this country was SAFE.  Later, impositions regarding proving the “efficacy” of the product, in line with the manufacturer’s claims, were added.  This became of particular interest as health care financial risk was born by third parties, including the Government under Medicare and Medicaid payments. 

Now, CER (Comparative Effectiveness Research”) has taken the FDA’s scope of authority yet farther as the research manufacturers must assume before and after a product is launched involves establishing more than just, “Can I prove that this product is more effective than a placebo?”  Defined in various ways, CER is described by the IOM as “the generation and synthesis of evidence that compares the benefits and harms of alternative methods to prevent, diagnose, treat, and monitor a clinical condition or improve the delivery of care. The purpose of the research is to help consumers, clinicians, purchasers, and policy makers to make informed decisions that will improve health care at both the individual and population levels.”

The American Recovery and Reinvestment Act of 2009 (ARRA) and the ACA reignited the federal government’s interest in CER.

There is a cost (which is not surprisingly added to the cost of the product) to prove safety and a cost to prove efficacy.  When you go to prove comparative efficacy, you are risking that you will lose.  It’s tantamount to betting your bank account at the craps table in Las Vegas because you cannot really be sure which way it will turn out. 

In fact, this CER craps table, has become part of the requirement under new federal requirements but sometimes the forest is lost for the trees.   For example, the Forbes article linked below cites TWO studies on diabetes drugs that concentrated on Safety (being no worse than placebo) but said nothing about effectiveness.  At what cost?    The author concludes, “Rather than mandating narrow studies of cardiovascular studies, we should be encouraging studies that let us know which regimen is best for which patients, based on what they actually do for patients.” 

He does not recommend ignoring safety, he’s just looking for an equally important conclusion.  I am sure there are also CER studies underway to answer his question.  

http://www.forbes.com/sites/harlankrumholz/2013/09/03/is-no-worse-than-placebo-good-enough-for-new-diabetes-drugs/

The other perspective on this is from the Heritage article linked below, referencing that this concept in the UK resulted in a system whereby CER was used to reject certain treatments for mostly budgetary reasons.

“CER use in the U.K. has been a far cry from what is implied by the rhetoric used to promote PCORI. Rather than focusing on the individual needs of patients, the United Kingdom’s National Health Service (NHS) uses comparative and cost-effectiveness information to limit options as a budgetary tool.

The NHS offers health coverage to all British citizens and determines which treatments will be covered and paid for, and under which circumstances. Decisions are based on “recommendations” by the National Institute for Health and Clinical Excellence (NICE), who’s stated purpose is to create clinical guidelines and standardize care using cost-effectiveness information, but the NHS is required to adhere to all of the recommendations made by NICE.

If a treatment is not covered, patients are able to go outside the NHS and receive it privately without regulatory or statutory obstacles—if they are able to afford this. (Because of Medicare’s restrictions on private contracting, American seniors would not have this same option.)” 
http://www.heritage.org/research/reports/2012/04/comparative-effectiveness-research-under-obamacare-a-slippery-slope-to-health-care-rationing

Thus, the benefits of CER (which may derive clarity for the practitioner to apply to individual patients) must be weighed against the need to treat each patient as an INDIVIDUAL whose needs, wants, and situations may require the flexibility which a system conformed to the latest CER may not allow. 

  Terri is a Senior Partner at Valiant Health, LLC, and founder of Cambria Health Advisory Professionals.  The thoughts put forth on these postings are not necessarily reflective of the views of her employers, clients nor other Valiant Health colleagues. Terri has had a varied career in health related settings including: 9 years in a clinical hospital pharmacy setting, 3 years as a pharmaceutical sales rep serving government, wholesaler, managed markets and traditional physician sales, 3 years working for the executive team of an integrated health system working with physician practices, 4 years as the director of pharmacy for a large BCBS plan, 12 years of experience as founder and primary servant of a health technology company which was sold to IMS Health in late 2007.  She has both a BS and a PharmD in Pharmacy and an MBA. 

Today’s Supply-Demand Challenges for Generic Pharmaceuticals

Terri Bernacchi, PharmD, MBA,Health Advisory Professionals 

In a world where we have come to rely upon the plentiful supply of low-cost, high-quality generic drugs, shortages and quality problems throw a definite kink into the goal of delivering needed medications to US patients.  Supply shortages stem from a variety of factors, some of which are related to stepped-up manufacturing quality audits by the FDA, the ferocity of competition between generic manufacturers with associated recent company consolidations, and increasing demand, in general.   In some cases, the brand manufacturer which innovated the drug has found it is no longer commercially feasible to produce and market the brand version of the drug.  Thus, without sufficient generic options available, providers are stuck with no supply or sometimes seeking importation from outside the US (if approved by the FDA) where unknown manufacturing quality problems could also be a factor of concern.  Sometimes the patient can be converted to an alternate (but not equivalent) drug; sometimes the needed but unavailable drug does not have a suitable substitute. 

The linked article by Wall Street Journal reporter Jennifer Corbett Dooren (see: http://online.wsj.com/article/SB10001424052748704680604576110613604195324.html )

mentions recent critical shortages of generic injectable cancer drugs and indicates that hospitals are struggling to manage their supplies.  These products may have very complex manufacturing processes which also lengthens the time it takes for other companies to flex and meet supply shortages;  in order to be approved as a producer, a manufacturer needs FDA approval to jump in to fill the gap, which also adds time and challenge to the equation. 

The number of reported drug shortages has more than tripled in the last five years, according to the FDA.  And a spokesman for the American Society of Health System Pharmacists has labeled this a “near-crisis” situation. 

Unfortunately, some of these supply problems are the direct consequence of consolidations and regulations which have made it harder to manufacture and compete for both branded and generic companies.  Some Congressional leaders, not surprisingly, think that more regulations and penalties may improve the situation.  In fact, they add to the burden and may actually make it harder to meet the demand.   

Lest you think this is just another hysterical sound bite in the news, please note that the FDA has a link that you can regularly follow to identify these shortfalls. “The drug shortage program, within the Center for Drug Evaluation and Research (CDER), addresses potential or actual shortages of prescription, over-the-counter, or generic drugs that have a significant impact on public health.”  The link takes a while to refresh so give the page a few seconds to be visible; it details for each short supply product the Drug Name, Company, Reason for Shortage, and Related Information guiding the reader through the details. 

http://www.fda.gov/Drugs/DrugSafety/DrugShortages/ucm050792.htm

The solution, I believe, lays in developing policies that encourage generic companies to prosper and thrive so that there is sufficient opportunity to manufacture and market these products in a quality way.  

Terri currently works for a large health sciences firm serving payers, pharmaceutical and device manufacturers and other stakeholders in health care as a Senior Principal in Managed Markets.  The thoughts put forth on these postings are not necessarily reflective of the views of her employer nor other Health Thought Leader colleagues.   Terri has had a varied career in health related settings including:  9 years in a clinical hospital pharmacy setting, 3 years as a pharmaceutical sales rep serving government, wholesaler, managed markets and traditional physician sales, 3 years working for the executive team of an integrated health system working with physician practices, 4 years as the director of pharmacy for a large BCBS plan, 12 years experience as founder and primary servant of a health technology company which was sold to her current employer three years ago.   She has both a BS and a PharmD in Pharmacy and an MBA.