The article (by the consistently excellent Tara Parker-Pope), “A Hurdle for Health Reform: Patients and Their Doctors,” makes an important point:

“Ultimately, for any reform to work, patients will have to change their behavior. Of course, everyone should continue to demand the best possible care. But we will have to accept that “best” doesn’t always mean the newest drug or the latest treatment. The looming question is whether patients are ready to embrace the realities of reform.”

Good point.

She then goes on to discuss various doctor/patient issues relative to healthcare reform, specifically comparative effectiveness. Ms. Parker-Pope writes:

“At the heart of reform is a plan to cut costs, in part by trying to discern which treatments really work. President Obama’s economic stimulus plan includes $1.1 billion for studies that will ask basic questions about the comparative effectiveness of expensive procedures versus less expensive ones. For instance, with certain kinds of injuries, does surgery work better than physical therapy? Are costly new drugs any more effective than their generic predecessors?”

Good questions.

And then she falls into the trap of how comparative effectiveness is “proven.” She writes:

“But when it comes to comparative effectiveness, the track record of the American public and their doctors is not encouraging. Even when such comparisons are available, we tend to ignore them. In 2002, for example, one of the largest government-financed clinical trials ever found that generic pills for high blood pressure worked better than newer drugs that were up to 20 times as expensive. But most hypertension patients still use costlier drugs marketed by pharmaceutical companies.”

Oops.

She refers to the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) study. And what she says is says isn’t so cut-and-dried. In fact, it's wrong and misleading.

Here’s what Michael Weber, MD -- one of the original ALLHAT investigators recently said:

“Using ALLHAT as an example of an “evidence gap” could be misleading, for the issue is not the information produced by ALLHAT, but rather how it’s interpreted and used.

So the claim of an evidence gap is not based on a disregard of evidence, but in fact demonstrates that the opposite is true. Clinicians apparently are aware of the full spectrum of evidence, not just selected portions promoted by a government agency. From the perspective of patients with hypertension, this surely is good news.”

Reporters need to be careful about the claims they make – just like drug companies.

Not surprisingly (in advance of the budget) light on details. No surprises.

Per healthcare reform, two words that may serve as tea leaves -- "down payment" and "affordable."

"Down Payment" = incremental.

"Affordable" = insurance reform.

Relative to "affordable," here's are a few paragraphs from the recent Robert Pear story in the New York Times:

Since last fall, many of the leading figures in the nation’s long-running health care debate have been meeting secretly in a Senate hearing room. Now, with the blessing of the Senate’s leading proponent of universal health insurance, Edward M. Kennedy, they appear to be inching toward a consensus that could reshape the debate.

“There seems to be a sense of the room that some form of tax penalty is an effective means to enforce such an obligation, though only on those for whom affordable coverage is available,” said the memorandum, prepared by David C. Bowen, a neurobiologist who is director of the health staff at the Senate Committee on Health, Education, Labor and Pensions.

Another question worth pondering is wither Medicare Advantage?

Here's the House/Senate report language that accompanied the $1.1 billion for a Federal Coordinating Council on Comparative Effectiveness:

"The conferees to not intend for the comparative effectiveness research funding ...to be used to mandate coverage, reimbursement, or other policies for any public or private payers,” and that funding shall be used to evaluate “the clinical outcomes, effectiveness, risk, and benefits of two or more medical treatments and services.” The conferees “further recognize that a ‘one-size-fits-all’ approach to patient treatment is not the most medically appropriate solution to treating various conditions.”

"CE" can mean so many things. It can also mean "Caveat emptor."

Doctors could soon be using a Star Trek-style device the size of a BlackBerry to check patients' genetic suitability to different medicines. A prototype of the hand-held device is already being tested by British scientists, who say it could be on the market in two years. The SNP (pronounced snip) Doctor is the kind of gadget that might by have used by Dr Leonard McCoy in the original Star Trek TV series.

From a drop of saliva or cheek swab it can analyse DNA to tell if a patient has the right genetic fit for a particular drug.

The Snip Doctor looks for known single nucleotide polymorphisms (SNPs) - single letter changes in the genetic code - that can affect an individual's response to medical treatment. Each year the NHS spends around £460 million dealing with the 250,000 patients who are admitted to hospital suffering adverse reactions to prescribed drugs. The unwanted side effects can vary in severity from dizziness and nausea to heart palpitations or loss of consciousness. The finished product will be an all-in-one device that can rapidly analyse a sample placed in its cartridge and flash the result up on a screen.

Being able to predict bad responses to drugs such as antidepressants or cholesterol-lowering statins would allow doctors to tailor dosages and types of medication to individual patients. Scientists at Imperial College London and its spin-out company DNA Electronics are now carrying out trials of the Snip Doctor's effectiveness.

That's nice -- but rhetoric won’t put more inspectors on the street. That takes the do-re-mi.

Representative Rosa DeLauro says she will introduce a bill that would take food safety away from the FDA and place those duties at a new Food Safety Administration within HHS.

But it's not where the responsibilities reside – it’s the budget available to do the job. And if you think the drug side of the FDA is under-funded (and it is) then get ready for this – the food side is even worse off.

(One former top FDA food safety official, when told he would have to “do more with less,” replied, “How about this – how about we do less with less.” He resigned shortly thereafter.)

When you fund CFSAN with peanuts -- you reap what you sow.

Check please.

Ms. DeLauro’s proposal (along with most of the others being offered) would give the FDA authority to order recalls, which are now voluntary.

Nice rhetorical flourish. But here’s the real deal – all recalls are “voluntary” (note quotation marks) but the companies being “asked” (note quotation marks) are always – like 100% of the time always -- compliant.

Change the verbiage, sure. But write the check.

And since Congress is paying attention to the FDA and the food side of the business, here’s something else to think about – dietary supplements.

In May 2007, the Supreme Court rejected an appeal from a unit of Nutraceutical International Corp. to overturn a Food and Drug Administration ban on its ephedra dietary supplements.

Nutraceutical sued the FDA in 2004 to block the agency's action on ephedra, arguing it was abusing its authority and misusing federal regulations in order to take action on the dietary supplement, which is generally regulated more like a food than a drug.

A U.S. district court sided with Nutraceutical, Salt Lake City, but the 10th Circuit overturned that ruling.

"This case offers a key test of whether the FDA will be required to observe the statutory boundary between foods and drugs,"

That ruling was good news for the public health -- but it raises urgent concerns as to why so-called "supplements" are regulated as food in the first place.

If Congress is looking at how the FDA regulates food (or even if it should continue to do so), our elected representatives should (indeed must!) debate significant reforms to DSHEA.

She has an enviable title, “Senior Genomics Advisor” and her task is to focus on the agency’s goal of providing the agency’s physician and scientists with the tools and personnel capable of high level analysis of complex genetic data. Liz will reside within the Office of the Chief Scientist.

The title is nice. The function is crucial. Now all FDA needs is the funding to aggressively address the issue.

Fund the Reagan/Udall Center now!

According to NICE, “Sutent provided a step-change in the first-line treatment of advanced and/or metastatic RCC and [NICE] noted that more than 20% of the public and patients that responded in consultation highlighted this impressive benefit from sunitinib.”

(More than 7,000 people are diagnosed with kidney cancer in the UK each year and approximately 3,600 people die from the disease.)

This reversal is effectively an acknowledgment that the agency hasn’t worked as intended.

And just what caused the the reversal? Why evidence, of course.

A spokeswoman for NICE said the organization was reevaluating Sutent because "there was more evidence submitted during a couple of periods of the appraisal process by manufacturers, which needs to be discussed by the [appraisal] committee.”

Couldn't have been anything else, right? Well, according to a report in The Guardian,

“The move follows British Health Secretary Alan Johnson's decision this month to overhaul the way new medicines are assessed for terminally ill patients. Denying cancer patients access to drugs that are widely available abroad has become a major political issue."

Here's what NICE Chairman, Sir Michael Rawlins had to say, "We must be fair to all the patients in the National Health Service, not just the patients with macular degeneration or breast cancer or renal cancer. If we spend a lot of money on a few patients, we have less money to spend on everyone else. We are not trying to be unkind or cruel. We are trying to look after everybody."

As Robert Jones (a retired Glaxo Wellcome executive and former member of EFPIA's economic policy committee from 1994 to 2006, and its chairman from 1994 to 2001) writes:

“At the root of NICE’s operations is a Benthamite approach to health benefits. For NICE, value equates to social utility, the optimisation of which informs all of its judgments. Some of NICE's decisions may seem cruel in human terms, and ill-advised in public relations terms, but there is an arid logic to them which can usually be seen at work.”

Utilitarianism isn’t a one-dimensional worldview. Consider Bentham’s comment that,
“It is vain to talk of the interest of the community, without understanding what is the interest of the individual.”

Is the Sutent decision a NICE breaker?

That’s good news. It means the message that FDA-approved generic drugs are safe and effective is finally getting some traction. And the cost savings are significant.

But, as usual, there are those who would use this news for their own selfish purposes. In this case it’s the Generic Pharmaceutical Association (GPhA).

Earlier this month, the GPhA applauded the introduction of HR 573, a bill that would prohibit the marketing of authorized generics during the 180-day generic exclusivity period. Kathleen Jaeger, chief executive of the GPhA, sees the proposed legislation as a way to close a “loophole” in the 1984 Hatch-Waxman Act that allows innovator life science companies “to delay generic competition by discouraging generic companies from challenging weak and potentially unenforceable patents." She praised the bill’s sponsor, Republican Jo Ann Emerson, and colleagues for “working to close this loophole for the benefit of consumers struggling with health care costs during these difficult economic times."

Well, if we’re all in this to help consumers control costs – then this bill would achieve precisely the opposite.

If the GPhA gets its way, the category of medicines known as “authorized generics” (also referred to as “branded generics”) will vanish — and drug prices for millions of Americans could go up by as much as 17%. (This calculation is based on a comparison of what consumers actually spent on generics during the 180-day exclusivity period to what they would have spent to purchase the same quantity of generics at higher prices in the absence of a branded generic launch.)

Historical pricing data shows that brand companies launch their generics at a 50 percent discount off retail price compared to a 30 percent discount experienced when a generic drug has no competition. If HR 573 passes, consumers and taxpayers over the next two years would realize about $8 billion instead of $13 billion in savings. Cui bono? The missing $5 billion will line the pockets of a handful of generics companies. That’s quite a cui bonus. This end-run around Hatch-Waxman is an extended index finger to the FDA, the FTC and judicial precedent. (A Federal Appeals Court made it clear that Hatch-Waxman allows for authorized generics.)

Over the next few years about $60 billion in brand drugs will become generic; $30 billion of that will be sold without competition for 180 days if Ms. Jaeger and Representative Emerson get their way.

No wonder this “modest proposal” is being greedily embraced by the generics industry and Big Pharma bashers. And greedy is hardly hyperbole since profits on generic medicines exceed 45% -- even when there is a competitive branded generic on the market.

We all call the existing legislation by its inside-the-Beltway designation, “Hatch-Waxman” – but let’s not forget that the full name of the law that brought the generic industry into being is the Drug Price Competition & Patent Term Restoration Act -- not the Generic Drug Company Guaranteed Profit Act. When the media and generic drug lobbyists conflate suspicious stalling tactics with legal and consumer-friendly market actions, neither the truth nor the public health are served.

According to the New York Times, “Nine dissident scientists at the Food and Drug Administration who say they were forced to approve high-risk medical devices sent a letter to President Obama on Monday stating that agency officials might have made them the targets of a criminal investigation into their complaints.”

If the FDA has undertaken such an investigation (and the agency will not confirm or deny), the reason is that these nefarious nine leaked confidential agency documents to the media. That’s a felony.

The Nefarious Nine are unhappy that their complaints about device approvals aren’t being addressed with greater alacrity. So, in their righteous indignation, they decided that their purity placed them above the law.

Unfortunately, not only will their behavior not speed up the agency’s investigation of their brief – it may very well slow it down.

Breaking the law is the wrong path to better regulatory oversight of medical devices. The ends doesn’t justify the means.

That would be the result of language inserted into the 2009 version of the Kohl/Grassley Physician Payments Sunshine Act.

New language in the bill proposes to give states authority to require disclosure or the reporting of information not required by the FDA.

Result: 50 state FDAs … and chaos.

Chaos for drug companies, certainly. But even worse -- chaos for patients and physicians. Imagine a doctor in New York getting different information on a medicine than a doctor in Michigan. Imagine a patient in Vermont getting different treatment than a patient in Arizona because their physicians weren’t sure who to listen to or what directions to follow.

Talk about emasculating the drug label.

And who should pharmaceutical companies go to with data and questions? 50 state health commissioners who may or may not have ever even looked at clinical trial data? Are there any state health commissioners who hold a technical candle to even a mid-grade FDA reviewer? Is there a state in the Union that employs a biostatistician? And how would states pay for these new professional employees? Likely source is lucre from lawsuits. And it's even more likely these professional services would be provided by outside “experts" -- the same folks who earn a nice living from being “expert” witnesses.

Speaking of expert witnesses, the Physician Payments Sunshine Act makes no provision for reporting fees earned for such activities.

That ain’t sunshine.

Here's the verbiage straight from the press materials:

For Patients Today – Broad Range of Health Care Solutions and Treatments: The new company will offer customers and patients a broad range of products for every stage of life. Unique and valuable insights will be gleaned from a portfolio that spans wellness and preventive care, such as vitamins and vaccines, as well as therapies for a wide range of illnesses and diseases, such as Alzheimer’s disease and cancer. We will leverage research across our portfolio and input from an extensive network of customer, physician and stakeholder relationships to accelerate, improve and expand the health solutions and treatments we offer.

For Patients Tomorrow – Robust Discovery and Development Program: The new company will have more resources to invest in research and development than any other biopharmaceutical company. We will have access to all leading scientific technology platforms – enhancing the opportunity to produce significant breakthroughs in key disease areas. As a result, we will be better able to help patients and invest in pursuing multiple avenues to address a wide range of unmet health needs.

At All Times – A Patient-Centric Business: We will operate small, distinct business units tailored to patients and customers that also benefit from being part of a premier global organization. Each business unit will oversee product development from early stage research to clinical trials to commercialization. This approach will allow for more customer input into the development process, rapid decision making and a better use of resources. As a result, we will have the ability to invest in long-term opportunities while optimizing near-term patient access to existing products.

"Patients Today." "Patients Tomorrow." "Patient-Centric." That's what I call real p-value.

The words are right. Now let's see what happens.

No. Big difference.

Cost effectiveness is what NICE (The United Kingdom’s National Institute for Clinical Excellence) does based on (among other things) the infamous $50,000 Per Year of Life QALY (Quality Adjusted Life Year).

Cost effectiveness assumes an additional year of life is worth about $50,000, the average price of a fully loaded Land Rover.

For example, NICE’s preliminary decision was that four new cancer drugs (to treat people with kidney cancer that has spread) -- temsirolimus (Torisel), bevacizumab (Avastin), sorafenib (Nexavar), sunitinib (Sutent) not be reimbursed by the National Health Service because, despite clinical evidence that these drugs can actually help, they weren’t “cost effective. In essence, NICE doesn’t think that these four drugs are a good value for the NHS.

(Currently, the only available treatment for metastatic renal cell cancer is immunotherapy. This halts the disease’s progress for just four months on average. But if people are unsuitable for immunotherapy, or it doesn’t work, that’s it. There’s no other treatment option.)

NICE agreed that patients tended to live longer when they were given these drugs. But when they put the data from the trials into their QALY-driven computer models, they found that the drugs cost a lot at £20,000 - £35,000 ($39,000 to $68,000) per patient per year compared to the benefit they brought patients - too much for them to recommend that the NHS prescribe these drugs.

Result? The government saves money and patients receive an expedited death sentence. And that’s not hyperbole.

That’s cost effectiveness.

Comparative effectiveness is different. Key word: “comparative.”

Comparative effectiveness strives to show which medicines are most effective for any given disease state. Is there a “more effective” statin? A “more effective” treatment for depression? Most of the world refers to comparative effectiveness (often referred to as “CE”) as Healthcare Technology Assessment (HTA).

But how do you compare two molecules (or three or more) that have different Mechanisms of Action for patients (otherwise known as “people”) who respond differently to different medicine based on their personal genetic make-up?

Comparative effectiveness in its current form leads to a “one-size-fits-all” approach to healthcare – which means that it doesn’t fit anyone all that well. The concept it good, but the tools are wrong. Comparative effectiveness relies heavily on findings from randomized clinical trials (RCTs). While these trials are essential to demonstrating the safety and efficacy of new medical products, the results are based on large population averages that rarely if ever will tell us which treatments are “best” for which patients. This is why it is so critically important for physicians to maintain the ability to combine study findings with their expertise and knowledge of the individual in order to make optimal treatment decisions.

Government sponsored studies that conduct head-to-head comparisons of drugs in "real world’" clinical settings are regarded as a valuable source of information for such coverage and reimbursement decisions -- if not for making clinical decisions. Two such studies, the Clinical Antipsychotic Trials in Intervention Effectiveness (aka CATIE), study and the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) study were two such “practice based” clinical trials, sponsored in part by the National Institutes of Health, to determine whether older (cheaper) medicines were as effective in achieving certain clinical outcomes as newer (more expensive) ones.

The findings of both CATIE and ALLHAT were highly controversial, but one thing is not – even well-funded comparative effectiveness trials are swiftly superseded by trial designs based on better mechanistic understanding of disease pathways and pharmacogenomics. And, since most comparative effectiveness studies are underpowered, they don’t capture the genetic variations that explain differences in response to medicines by different patients.

But it’s important to move beyond criticizing comparative effectiveness in its current form, and instead focus on creating a policy roadmap for integrating technologies and science that is more patient-centric into comparative effectiveness thinking.

Much the like the U.S. Food and Drug Administration created something called the Critical Path Initiative to apply 21st-century science to accelerate the development of personalized medicine, another national goal should be to create a Critical Path Initiative to apply new approaches to data analysis and clinical insights to promote patient-centric healthcare.

Why? Because comparative effectiveness should reflect and measure individual response to treatment based on the combination of genetic, clinical, and demographic factors that indicate what keep people healthy, improve their health, or prevent disease. First steps have been taken. For example, the Department of Health and Human Services has invested in electronic patient records and genomics. Encouraging the Centers for Medicare & Medicaid Services to adopt the use of data that takes into account patient needs would complement such efforts.

We need to develop proposals that modernize the information used in the evaluation of the value of treatments. Just as the key scientific insights guiding the FDA critical path program are genetic variations and biomedical informatics that predict and inform individual responses to treatment, we must establish a science-based process that incorporates the knowledge and tools of personalized medicine in reimbursement decisions: true evidence-based, patient-centric medicine.

For instance, the FDA, in cooperation with many interested parties, has developed a Critical Path opportunities list that provides 76 concrete examples of how new scientific discoveries in fields such as genomics and proteomics, imaging, and bioinformatics could be applied during medical product development to improve the accuracy of the tests used to predict the safety and efficacy of investigational medical products.

We need a Critical Path for Comparative Effectiveness to begin the process of developing a similar list of ways new discoveries and tools (such as electronic patient records) can be used to improve the predictive and prospective nature of comparative effectiveness.

It’s a complicated proposition—but such a body’s goal is as simple as it is essential—cost must never be allowed to trump care, and short-term savings must not be allowed to trump long-term outcomes Just as we need new and better tools for drug development, so too do we need them for comparative effectiveness measurements.

Today, comparative effectiveness is a short-term, short-sighted, politically-driven policy that results in one-size-fits-all medicine. While it may provide transitory savings in the short-term, current strategies result in a lower quality of care that result in higher healthcare costs over time.

Restrictive formularies and health care systems that deny patients access to the right medicine in the right dose at the right time but pay for more invasive and expensive procedures later on have their priorities upside down. Attention must be paid. If the devil is in the details (and it is), it’s time for a deep dive beyond simplistic and self-serving “comparative effectiveness.”

A health technology assessment model for the 21st Century should reflect and measure individual response to treatment based on the combination of genetic, clinical, and demographic factors that indicate what keep people healthy, improve their health, and prevent disease. A rapidly aging society demands a new healthcare paradigm capable of providing for its needs in the 21st century. Equality of care must be matched with quality of care.

In an era of personalized medicine, one-size-fits-all treatments and reimbursement strategies are dangerously outdated. We are early in this debate, but at least we can all agree that this is not, and must not be exclusively, a debate about saving money. It must be about patient care.

Currently, applicants submit studies demonstrating that the rate and extent of absorption of a generic drug meets bioequivalence limits, but additional bioequivalence studies conducted on the same formulation typically are not submitted. These include studies that failed to meet passing criteria, as well as multiple successful studies. The agency infrequently sees this additional data and is generally unaware of the existence of such studies.

Applicants also must submit data in an annual report on all post-marketing bioequivalence studies for an approved drug product formulation during the annual reporting period.

SCRIP World Pharmaceutical News reports that, “The agency notes that if it receives failed bioequivalence studies for a given application, it might make a different decision about whether to approve the generic than if it had received only the pivotal passing study.”

The FDA is limiting the additional studies to those conducted for the "same drug product formulation,” rather than requiring submission of all studies conducted with developmental formulations. "Same drug product" is defined as the formulation of the product submitted for approval, and any formulations that have minor differences in composition or manufacturing method but are similar enough to be relevant to the agency's bioequivalence determination. The FDA intends to issue draft guidelines giving specific examples of formulations it considers to be the same drug product.

Attention must be paid to the issue of bioequivalence -- particularly by those at the WHO and elsewhere who are toying with the idea of "clinical equivilence" for follow-on biologics.

What the Torti appointment does demonstrate (IMHO) is a vote of confidence on the part of the incoming administration in the agency's career staff -- and a polite "mind your business" to certain members of Congress. After all, it was only last month that Representative Bart Stupak wrote to President-elect Obama recommending, " ... not to appoint any current senior FDA employee as Commissioner or Interim Commissioner of the FDA."

Thanks Bart. But no thanks.

AMID CONCERN that money from drug makers was unduly influencing medicine, Governor Deval Patrick recently signed a law aimed at shedding light on the relationships between pharmaceutical firms and healthcare practitioners.

The Department of Public Health, which is responsible for enforcing the law, recently submitted the regulations it plans on implementing to the Public Health Council, which will vote on it in February.

Along with banning certain gifts, the new regulations would require pharmaceutical companies to disclose payments above $50 made to doctors, scientists, and other medical professionals. This information will be posted on the Internet.

The Department of Public Health has decided, however, to exempt medical research funding from the disclosure requirement. This move should be applauded, as it protects Massachusetts' thriving pharmaceutical industry and ensures that patients receive the best possible care. The Council should vote to make the exemption official.

Transparency is a good thing, of course, so lawmakers' efforts to ensure that patients know about financial ties between drug firms and healthcare providers are understandable. Indeed, this move came on the heels of a similar step by the pharmaceutical industry itself, which issued strict new rules governing how drug representatives pitch their products to physicians.

Such restrictions, however, should be limited to a company's marketing efforts. Funding for medical research is a different matter. Many of Massachusetts' leading academic labs are conducting research in partnership with pharmaceutical companies. Drug development depends on this sort of cooperation.

Plus, forcing pharmaceutical firms to disclose information about research funding implies that there's something wrong about the practice. Consequently, the doctors and scientists who receive research support from drug firms could be stigmatized. Fearful of jeopardizing their reputations, this could motivate many to leave the state and give up on their research projects.

This would make a bad situation even worse. According to the Massachusetts Medical Society, nearly a quarter of practicing physicians either already have plans to leave the state or are considering leaving because of burdensome regulations. This number should send chills down Bay State legislators' spines.

Massachusetts' pharmaceutical firms employ around 55,000 workers. Between 2000 and 2005, the state lost nearly 100,000 private-sector jobs - but the pharmaceutical industry created over 6,000 new positions.

There are more than 5,000 drug trials being conducted in Massachusetts, making the state one of the country's leaders in medical research. But just like beleaguered doctors and scientists, Massachusetts' pharmaceutical companies could decide that the state's regulatory environment has grown too hostile and move elsewhere.

Onerous regulations also add to a company's operation costs. Such costs eat up research budgets - choking off investment dollars into new drugs and treatments - and get passed onto consumers in the form of higher drug prices.

Instead of making life harder for pharmaceutical firms and the medical profession by mandating public disclosure of research grants, the Commonwealth should be looking to make life easier for such a valuable sector of the economy.