It was reported yesterday that Pfizer will stop doing research and development in heart disease, anemia and osteoporosis to concentrate in other areas such as cancer, diabetes, and immunology/inflammatory diseases.

This is interesting since Pfizer has (and had) a large number of products in heart disease, including Lipitor, and pharmaceutical companies have typically continued to do research in areas where they have had products because they have established sales people who are knowledgeable about the disease area and have relationships with clinicians in those areas.  The countervailing force is that many effective medicines to treat heart conditions (like high blood pressure and high cholesterol) are available in generic forms and thus the value bar (benefit/cost ratio) that new medicines must reach to be competitive is much higher than when they competing against other non-generic medicines.

However, one common and very expensive heart condition where better medical treatments are needed is heart failure - often called congestive heart failure (CHF).  According the the National Heart Lung and Blood Institute, 5 million Americans have heart failure, and 300,000 die from it each year.  The costs for these patients are very significant: Total costs for treating heart failure in the US are estimated to be $34.8 billion in 2008, and Medicare spent $4.7 billion for hospitalizations related to CHF in 2006.

The chart below from the Centers for Disease Control and Prevention shows the rate of hospitalization (per 1000 people) for heart failure in the US by age group over the years 1979-2004 - clearly a growing problem.

 Hospitalization Rate (per 1000 people) by Age Group for Heart Failure
1979-2004

So what does this mean for better treatments for CHF? According to the pharmaceutical industry’s web site database, there are currently 35 therapies in clinical trials for heart failure or congestive heart failure - including 3 based upon stem cell therapies, 1 based upon cell transplantation, and 1 using gene therapy.  (This compares to the 105 therapies in development for cancer, and 81 for pain.)  So I guess there will continue to be new treatments developed for heart failure, just probably not by Pfizer.  But, recognizing that there are lots of medical problems and limited resources need to be prioritized, will this be OK for current and future patients with heart failure?

Companies allocate and prioritize research and development resources according to three fundamental factors:

1. Unmet Medical Need
2. Scientific Opportunities and Discoveries
3. Market Potential

It is this last one that apparently Pfizer has decided has decreased, so they will be putting their resources into other areas where the combination of all three factors looks more appealing.  As long as all the research-based biopharma companies don’t make those decisions in the same direction (i.e. into and out of the same diseases), then research resources will likely be allocated in a reasonable way to meet societal needs. In that way the needs of people with heart failure will be balanced against those with cancer, chronic pain, diabetes, neurological diseases and immune dysfunctions - which is what society and patients really should want, since people often have multiple diseases or medical problems, so they should want new and better treatments for all of them.

Addendum: The memo from Pfizer’s R&D leadership about their strategic realignment has been posted by Forbes - click here.

One of the challenges for improving the healthcare system is creating a vision for what is achievable in a timeframe of months or years.  The first step for creating such a realistic vision is to understand how progress has been made in the past.

A microcosm of such progress was described in a recent article in The Economist.  This article describes advances in our understanding of stomach ailments – one of my favorite areas of biomedical progress because in the last several decades dramatic changes have occurred in our basic knowledge about this area, and so many people can relate to stomach problems.

The most significant change occurred in 1982 when two Australian scientists disproved the dogma that because of its very acidic pH the stomach was sterile.  They showed that the H. pylori bacteria could live in the stomach and cause the stomach inflammation associated with an upset stomach.  Subsequent research showed that H. pylori could be the cause of ulcers and stomach cancer. Following those discoveries, medicines were developed to change the pH of the stomach to treat the stomach inflammation and eliminate the H. pylori.

While lowering the acidity of the stomach with medicines would often improve symptoms, it also raised the question about what bacteria might be able to live in the stomach under less acidic conditions?  This question is more intriguing because it has been observed that when people taking medicines to lower their stomach’s acidity stopped taking these medicines, they have a resurgence in their symptoms.  This could be because their stomach had become accustomed to the less acidic conditions and then reacts to the renewed acidity; Or it could be because the bacteria that were living in the less acidic stomach are not happy with the greater acidity; Or perhaps the H. pylori that had been struggling in the less acidic stomach multiply very happily with the return of the acidic conditions.

H. pylori – Obesity and Asthma
The Economist article discusses some even more interesting ideas about the role of H. pylori in the stomach.  For example, they cite researchers who speculate that the elimination of H. pylori from the stomach may be linked to rising rates of obesity and cancer in the esophagus. These researchers at NYU School of Medicine also found that children who had not been infected with H. pylori were more likely to have asthma.  The article summarizes these observations with the speculation from NYU’s Dr. Blaser that perhaps H. pylori should be viewed not as a pathogen, but rather as a symbiotic organism “that is sometimes helpful and sometimes harmful.”

One of Dr. Blaser’s key observation is that H. pylori appears to not just be a passive resident of the stomach, but may actually regulate the stomach’s acid levels to keep the stomach’s pH in a range the bacteria prefer.  However, the substance that H. pylori secretes to get the stomach to produce less acid may be toxic to the stomach and result in ulcers and local cancers.  Thus, while eliminating the H. pylori would eliminate the toxic source of ulcers and cancers, it can also allow the stomach to produce too much acid – which can lead to cancer of the esophagus, as well as “acid reflux disease,” a.k.a. “heartburn.”

The H. pylori-obesity link is based upon the possibility that the bacteria modify the secretion of certain hormones effecting how people feel hungry, and the H. pylori-asthma link is based upon the effects the bacteria may have on children’s developing immune system.  (See The Economist article for more information about these areas.)

Conclusions
These findings lead to the conclusions that perhaps treating stomach ailments and preparing peoples’ stomachs for healthy lives should be based upon their genetic makeup, and seeding children with strains of H. pylori that don’t produce the toxins that can lead to ulcers and stomach cancer, could benefit them without doing harm in the long run.

Overall, this is a great example of how once more knowledge is obtained about a disease and the relevant human physiology, scalpel-like treatment and prevention strategies can be developed and implemented.  Of course, educating clinicians, patients, payers and others about these advancements – and why they are important – are also important challenges, because improving health care treatments and our healthcare system involves not just determining what should be done, but also how to actually accomplish those things.

Cost containment is becoming an increasingly powerful force in shaping the environment for life sciences companies - as well as other parts of the healthcare system.  In addition, more sophisticated tools for analyzing and demonstrating the clinical and economic value of medical treatments are making it more challenging for life sciences companies to communicate the value of their new products to all types of audiences, including clinicians, payers, patients and regulators.

These new tools and the changing environment are requiring life sciences companies to think about developing more sophisticated messages to reach these audiences. I recently recorded a short 6 minute discussion about these topics with Jeff Sandman, CEO of Hyde Park Communications - where I am also a Senior Counselor.  Click on the icon-link below to listen to our discussion.

And as always - if you have any comments on this topic - please feel free to share them.

An article in the July/August Health Affairs about Massachusetts health plans implementing Pay-for-Performance (P4P) incentives for physicians raised more questions than it answered.

The study found that P4P programs from 5 private sector payers “wasn’t associated with greater improvement in quality” compared to the overall upward trend in the factors measured.  But the study didn’t address some overarching questions and basic realities about P4P, such as:

• How the payers P4P incentives to the physician groups was actually translated into incentives for the individual physicians - or smaller groups of physicians inside the larger groups?
• How the P4P incentives compared to the other financial incentives the physicians are facing?  For example, seeing more patients or doing more procedures could increase their income more than meeting the P4P standards. (The Health Affairs article states that P4P incentives for Massachusetts physician groups averaged 2.2% of their income.)
• The quality measures used in the study were all performance based, rather than actual outcomes, e.g. cholesterol screening rates rather than patients’ actual cholesterol levels, HbA1C screening rates in diabetics rather than their actual HbA1C levels, or asthma medication use for children ages 5-17, rather than ER visits or hospitalizations for these same children.  What impact does that has on physicians’ behavior, and the value of changing their actions to meet these process standards?  Would physicians be more responsive to incentives tied to clinical outcomes?

Making Incentive Programs Successful:
While the study concluded that the P4P incentives program instituted in 2002 may not have produced dramatic changes in the HEDIS process measures, that does not mean  they were ineffective or that P4P is not a useful tool.

First, while collecting process measures data is easier, since clinical outcomes are what patients (and their physicians) should really care about, shouldn’t P4P incentives be based upon actual clinical outcomes? Process measures are easier to monitor by using billing data, but as the prevalence of quality electronic medical records systems grows, collecting and analyzing data about clinical outcomes will become much easier.  In addition, measuring a small set of any factors – process or outcome – presents the pitfall of driving physicians to focus on those diseases and measures to the exclusion of other important things.  For example, in the Health Affairs study, there are a number of preventive services in the process measures, but what about flu vaccinations, colonoscopies or smoking cessation?  This “managing what is being measured” behavior is why the number of factors used for P4P incentives should be as broad as possible.  (But this does not mean that they all have to be measured at every interval, or for every compensation period.)

Second, as any psychologist (or parent) will attest, the time between the actions and the reward (or penalty) is very important for changing behaviors. The Health Affairs article indicates that the bonuses are paid to the physicians groups annually.  Having the incentives paid annually, (or even quarterly), would be unlikely to provide adequate feedback to physicians to prompt them to change their behaviors.  An alternative blended methodology would be to provide physicians feedback on their actual performance against many of the possible measures on a weekly or bi-weekly basis, while making the P4P payments on a monthly or quarterly basis.

Third, many large companies structure their bonuses for their senior managers around a minimum of 20% of compensation.  If incentives for P4P programs only represent a small percentage of physicians’ income, then it would be unlikely to change their behaviors – particularly if they can make up for any lost income by increasing volume.  However, if physicians are being paid a fixed (capitated) amount per month to provide a certain set of services to a patient group – either primary or specialty care – then the volume part of the equation disappears, and P4P programs could be much more effective, even at a lower fraction of their potential income.

And lastly, and most simply, the insurers would not be spending time and money developing and implementing these programs if they didn’t think they provided some benefit – even if it is only financial - so they must be getting some benefits, or at least learning some things to make these programs beneficial in the future.

Conclusions:
18 years ago I wrote a book chapter that focused on structuring incentives for physicians.  Since then it has been hard to move payers and clinicians toward using more focused financial incentive systems.  But the P4P concepts are important, and to be successful they need to be implemented in a way that works for payers, physicians, and patients.  Unless these and other stakeholder groups buy-in to the purpose and practice of such incentives systems, they are unlikely to have the desired effects.  And the result will be more of the same – rising costs, variable quality, and limited access for many patients.

After writing about Follow-On Biologics in a recent posting, I saw a notice about Health Canada’s proposal for how they would approve biologic products that are similar to already approved biologics whose patents have expired. They call these products Subsequent Entry Biologics (SEBs), and the proposal is open for public comment from March 14, 2008 until April 16, 2008.

While the draft guidance is lengthy, it does strike an overall well-balanced tone:

• “SEBs are not ‘generic biologics’”
• Approval of an SEB does not mean it can automatically be substituted for the original biologic that it is “similar” to
• Comparative studies will be required to generate data showing similarity to the original biologic in terms of quality, safety and efficacy

In many ways, the draft guidance is similar (no pun intended) to the process the US FDA used to approve some generic drugs prior to the 1984 Hatch-Waxman Drug Price Competition and Patent Term Restoration Act. (This was the law that created the abbreviated new drug application (ANDA) process which allowed generic drugs to only demonstrate bioequivalence, and obviated the requirement that they replicate the original drugs safety and efficacy trials.) By referencing published studies about the innovator drug as proof of safety and efficacy, these so called “Paper-NDAs” allowed generic companies to be approved much faster and more cheaply.

Health Canada’s “paper biologic licensing application” like proposal, would allow them to rely on published information about the original biologic, while also handling each SEB application individually to decide what additional studies need to be done to demonstrate quality, safety and efficacy of the SEB.

As I pointed out in my previous post, there are many levels of structural and biological complexity with biologic treatments, so Health Canada’s draft approach seems very appropriate and reasonable.

What do you think?

I’ve been trying to figure out how to write something meaningful about the many reports over the last several months about the safety, costs and quality of medicines. I finally concluded that rather than a too lengthy blog post, a series of snapshots would create a good description of the situation - sort of like a slide show rather than a feature film:

Safety of Generic Drugs: A recent LA Times article discussed patients who had adverse reactions when switched from a brand name to a generic medicine. This article includes physicians’ experiences with several types of generic medicines, e.g. for epilepsy, depression, high blood pressure, irregular heart rhythms, and to prevent rejection of organ transplants. Aside from epilepsy, these are different types of medicines from “narrow-therapeutic-index” (or NTI) medicines which have a small dosage range which produces the desired clinical effects before causing known side-effects. Also, the current safety concerns are not related to what happened in the early 1990s, when some generic companies where caught submitting false safety data — they used the brand name medicine for the bioequivalency testing required by the FDA instead of actually testing their generic versions. (Yes, people went to jail.)

Safety of Medicines Imported into the US: Medicines imported from other countries have raised safety concerns because of lack of quality oversight and the murkiness of the chain of custody. These concerns have recently been highlighted by the contamination problems of herparin from a factory in China, and reminds me of how the head of the Chinese State Food and Drug Administration was convicted last summer of taking bribes in exchange for approving generic drugs that hadn’t had the required testing. (They sentenced him to death, and actually hanged him shortly after he was convicted.)

Fake Medicines: Whether produced in the US or someplace else, there is a growing market in fake medicines. The economic incentives are huge, and unlike illegal recreational drugs, the risk of your customer to violently come after you for selling substandard products is very low. There have been cases of fake medicines made here in the US, and the World Health Organization estimates that up to 30% of medicines in some parts of the world are fake.

Fake antibiotics are of particular concern: Fake antimalarial medicines sometimes contain tylenol or asprin which lowers the malarial fever without actually treating the infection - so people think they are getting better while they continue to spread the infection. And subpar medicines that only contain a fraction of the antibiotic promote the spread of resistant strains of bacteria. So fake or substandard antibiotics may actually be worse than no pills at all.

Even the New York Times editorial board recognized the global dangers of fake medicines in a December 12, 2006 editorial.

Follow-On Biologics: There has been a lot of interest in new versions of biologic treatments. These have many names: generic biologics, biogenerics, biosimilars, and follow-on biologics. One of the great confusions with this issue is that drugs and biologics are different categories of treatments. Because of their different chemical natures they are covered by different parts of US law, and until recently they were regulated by separate divisions of the Food and Drug Administration.

While drugs and biologics are both made up of atoms, drugs are much simpler, generally much more stable, and produced by chemical reactions starting from raw chemical ingredients or from a natural compound purified from a plant or animal source. Biologics on the other hand are much larger compounds (often proteins), and are generally made by living cell cultures (or in some cases whole animals), with the active drug is purified from that source.

The different structural complexities of drugs and biologics is because small molecular drugs are based upon a limited number of configurations of their atoms - usually 1, or 2, or sometimes 4 variations that are either mirror images of each other, or forms that exist in a predictable equilibrium. Biologics on the other hand have 2 or 3 more levels of structural complexity beyond that found in small molecules. (See here for a description of the primary, secondary, tertiary and quaternary structures of proteins.) Printing is a good an analogy to the structure of drugs and biologic, with a drug being like a sentence, where the series of letter and punctuation defines it. Conversely, a biologic is a like a book, where the construction of the paragraphs and chapters are its secondary and tertiary structures, and the footnotes, references, bibliography and appendices are the quaternary structures. Obviously it is easy to copy a sentence to look like the original, but replicating a book, with the same pagination and structure is much more complicated.

As a semi-avid baker, another analogy I like for the difference between drugs and biologics is a comparison between baking powder and eggs. Baking powder is a combination of chemicals designed to produce a chemical reaction to yield the right chemical/baking effect when used in the right amount. It is generally stable, and lasts for a long time when not exposed to air. Eggs on the other hand, can easily spoil (particularly if the shell is cracked), and have two major parts - the yolk and the white. The whites are mostly protein, and yield very different results depending upon how they are used. For example, adding raw egg whites to cake batter produces a very different result than if they are heated first and then added. (Think about the difference between an angle food cake and a quiche.) Egg yolks are mostly fat are are nicely separated from the whites. Mixed with the whites they cook up one way, and separately are used in pudding, custards, etc.

Adverse Drug Events and Medical Errors in Hospitals: There have been many studies about medical errors in hospitals and how many of those relate to adverse drugs events because the patient received the wrong medicine or the wrong amount of the medicine. These studies clearly point out the value of electronic medical records which avoid handwriting mistakes, and can automatically check for drug-drug interactions. Another important organizational feature of hospital care is the integrated medical team that includes experienced pharmacists and nurses. Such teams ensure rapid and accurate communications about treatment issues among the clinicians writing the prescription and those dispensing it or delivering/administering it to the patient.

Conclusions: Medicines are extremely potent, they can be very complex, and they are central to one of the mantras of clinically and cost effective care: “The right treatment, to the right patient, at the right time.” Electronic medical records and electronic prescribing systems certainly can help achieve that goal, while substituting non-identical medications, or enabling the distribution or use of substandard of fake medicines undermines movement towards that goal.

The US Medicare Payment Advisory Commission (MedPAC) recently released a report on “Creating a Center for Evidence-Based Medicine” that was prepared by an outside analysis group. Before dissecting the MedPAC report, let me just lay out some of the more controversial aspects of evidence-based medicine (EBM):

• How are the results of EBM research used for coverage or payment?
• Are the EBM conclusions based upon reviews of prior studies or on research done specifically for the EBM analyses?
• Are the EBM conclusions relevant only for a clinical research situation, or do they reflect real-world practices?
• All medical practices evolve and “best medical practices” are reflected last in textbooks….. after they appear in journals….. after they have been presented at meetings….. after research has been done to understand these practices. How do EBM analyses account for this timeliness factor and include the latest advances?
• How does the EBM analytical process question the validity of its own assumptions - particularly the perceived benefit by patients, or calculations about the “value” of the outcomes from a treatment?
• And related to the previous question - Do the EBM analyses reflect only the benefits to the individual patient or spending by the health plan, or do they include benefits to other parts of society, i.e. families, employers, etc.

Overall, the question is, how does EBM research translate information about the outcomes produced by various medical treatments into better medical practices? When I was in medical school, this was the purpose of textbooks and professors. If national (or global) EBM organizations can accelerate this process and make it more accessible (possibly using new information technologies), then that’s probably fine. But if its functions are subordinate to the cost reduction agendas of healthcare payers, (and this leads to rationing of healthcare services and products based more upon cost than real value - which has been the case with virtually all existing EBM organizations), then a US Center for EBM will become another part of our healthcare system’s problems rather than a step towards solving them.

Below is some commentary on the MedPAC report and some of the existing EBM organizations it discusses:

The MedPAC report outlines several layers of functions for the proposed Center for EBM:

1. Practice Identification and Review
2. Dissemination (of information and conclusions)
3. Training and Technical Assistance
4. Practice Adoption (via education and working with stakeholders)
5. Clinical Outcome Review

Clearly #4 is the key to making EBM research findings useful, and the report cites three critical issue for the voluntary adoption of practices found to be beneficial via EBM research:

1. Credibility
2. Stakeholder Involvement
3. Viable Economic Incentives

Of these, #3 is the most contentious, and the report notes that, “Since economic incentives often represent a threat to opponents of creating a centralized organization of the type described here, it may be desirable to leave that implementation to policy makers rather than treating it as the role of the organization.”

As noted above, a major controversy about “Evidence-Based Medicine” (EBM) is how it is used to make coverage and reimbursement decisions. The report recommends that EBM research and these decisions be kept separate, but the experience with EBM organizations in other countries, and in US health programs like Medicaid and the VA, has been that this is often not followed in practice. On one end is the Department of Veterans Affairs Medical Advisory Panel (MAP) which - as part of the VA’a National Formulary development process - is tasked with performing evidence-based reviews of therapeutic drug classes “that may or may not lead to national standardization contract initiatives.” While this sounds like a rationale and analytical process, my experience with this process is that the MAP does analyses to justify the inclusion of the least expensive medicines on the VA’s formulary.

Because the VA is only about 5% of the US healthcare market, it doesn’t have a sweeping impact on medical care in the US. However, it often goes on the record saying that its methodologies should be adopted by Medicare and private insurers - something that would have much greater implications.

The MedPAC report also talks extensively about the National Institute for Health and Clinical Excellence (NICE). This is one of the most studied EBM-type organizations. While unlike the VA’s MAP, NICE is not technically part of the UK’s National Health Service (NHS), it is created and funded by the British government - so just as two brothers are not the same person, they receive their allowance from the same parents. While the MedPAC report generally praises NICE, the real world experience of patients and companies is somewhat different, and in the global discussion of healthcare policy and economics, it is often cited as a classic fourth hurdle for accessing treatments, i.e. it has become the NHS’s de facto rationing resource.

And one final note of concern. In a previous post, I discussed the very low attendance at a session on Comparative Effectiveness (a type of EBM research) at the annual meeting of the American Association for the Advancement of Science (AAAS). If at a meeting with thousands of researchers, almost none were interested in this topic, what does that portend for the ability of a national EBM organization to conduct independent and analytically driven research without undue political and financial influences?

Have you seen payers pushing clinical practice recommendations under the guise of EBM when they were clearly financially driven initiatives to limit access to certain treatments (a.k.a. rationing), and would produce lower quality care for patients or just chew up the clinician’s time trying to navigate the additional barrier to getting the best care for patients?

What are your thoughts?

I attended the annual meeting of the American Association for the Advancement of Science today to hear a session titled “Health Economic Evaluations of Medical Technologies: Is the Cost Worth the Cure?”  The topic of this session was really about comparative effectiveness of medical interventions - particularly pharmaceuticals. The panel was a substantial group of physicians and health services researchers/regulators:

• Milton C. Weinstein, Harvard School of Public Health
• Michael F. Drummond, University of York, United Kingdom & NICE (National Institute for Health and Clinical Excellence)
• Jeffrey Kelman, Chief Medical Officer at CMS
• Marc Berger, Eli Lilly
• Tracy A. Lieu, Harvard Medical School and Harvard Pilgrim Health Care

The most impressive thing about this 3 hour session was that at a meeting with thousands of attendees, there were 12-15 people in this session.  Clearly the organizers had expected more, since the room had space for a couple of hundred.

Despite the small audience, the panel gave interesting - if not too in-depth -  presentations which at times delved into jargon about programs such as Medicare Part D, and unfortunately didn’t engage in speculation about the future of comparative effectiveness for decision making about the allocation of resources for healthcare services or research.

What was clear, is that (as I mentioned in an earlier post), comparative effectiveness is something here to stay.  The question remains to see how it will be used in the future by payers (particularly in the US), and how this will effect the quality of care, and the direction and intensity of research activities.

I have been helping the Medicare Rights Center (MRC) with some appeals of Medicare Part D plans denying coverage for off-label uses of FDA approved medicines. These denials are based on a very detailed provision in the 2003 Medicare Modernization Act that the Centers for Medicare and Medicaid Services (CMS) interprets to mean that Part D can only cover FDA approved medicines for off-labeled uses that are listed in at least one of three specific compendia.

I became involved with the MRC’s work on this issue because as a Congressional staff person I had helped write a 1993 law that expanded coverage for cancer treatments under Medicare Part B (that’s “B” as in ball) to specifically include off-label uses listed in the compendia OR supported by articles published in peer reviewed literature. (The Department of Health and Human Services developed a list of acceptable peer reviewed journals.) This process has worked well, but what it means now is that off-label uses of medicines to treat cancer supported by peer reviewed literature are covered under Medicare Part B, but NOT under Part D (that’s “D” as in drag).

For those interested in more details: The general difference between prescription drug coverage under Medicare Parts B and D is that Part B pays for medicines that patients cannot give to themselves, (so-called not “self-administerable” forms of medicines), while Part D pays for pills (and other forms of medicines that are self-administerable). However, the 1993 law required Part B to cover pills-type medicines to treat cancer if they are the same chemical medicine that Part B would otherwise pay for in an infusion form. Therefore, almost all oral medicines are covered under Part D.

Without getting into too many details of federal law, the issue for the MRC’s appeals comes down to how the Medicare Part D law references Medicaid’s definition of “medically approved indication” in directing what medicines are covered in what situations. The problem arises because Medicaid’s “medically approved indication” definition does not include coverage based upon peer reviewed literature - even though State Medicaid plans can include that coverage - and over 40 states do!

While this is a narrow situation, its impact on an individual can be huge - potentially representing of thousands of dollars per year per person. Medicare Part D says these costs are not their responsibility. State Medicaid programs (many of which would pay for these medicines for patients if Medicaid was their primary insurer) say these costs are not their responsibility since Medicare should be paying for them. So individuals are left to pay for these medicines themselves. And since Medicare doesn’t even “count” this spending towards the patient’s “drug spending,” it doesn’t move them through the Medicare Part D donut hole into the catastrophic coverage zone, where Medicare Part D would at least pay most of the costs of all their other medicines.

The Medicare Rights Center is handling a number of appeals on this issue, and is also involved with other groups trying to clarify the underlying law. If you have any other situations like this, I’d like to hear about it. You can also contact the MRC, although I understand that because of resource limitations, they are not taking any more specific Part D off-label appeal cases. However, they do have an appeals handbook and other Part D resources for physicians and patients [See halfway down the page under “Using Your Drug Plan.”]

What do you think about all this?