In otherwords,  the drug is safe and effective as prescribed for the vast majority of patients but since we never know if everyone who gets it will learn about their risk of heart disease we should take the medicine off the market. 

 Is it possible that the NEJM thinks doctors who are prescribing Meridia are too stupid or uninterested in potential medical malpractice suits to determine if someone might be at risk?  I don’t think so.  If every medicine that carries a CV risk was yanked from the market for that reason, you would have to take hundreds of drugs out of commission, including every pain killer.      The editorial's authors also assert that "the heart risk associated with Meridia is not justified by the weight loss seen in the study -- about 9.5 pounds (or 4.5 percent of initial body weight) after one year, on average," CNN /Health.com (9/2, Harding) reports.

And of course Steve Nissen has an informed judgment on the issue..
 Steve Nissen, MD, "a cardiologist at the Cleveland Clinic Foundation who has been a vocal critic of recent FDA handling of drug safety concerns, agrees," according to Time (9/2, Park). "We've got a drug here that shows little benefit -- a few pounds of weight loss -- and we trade that for a 28% increased risk of heart attack and 36% increased risk of stroke."

 Actually the study concluded: "nonfatal heart attacks occurred in 4.1% of sibutramine users and 3.2% of the placebo group, and nonfatal strokes occurred in 2.6% of sibutramine users and 1.9% of the placebo group,"  

 That’s actually a relative risk of 22 percent and 27 percent – or increase in risk of about 1 in 100000 --  but who’s counting? 

 http://www.diahome.org/DIAHome/Home.aspx

 The other example of ignoring facts comes from the study of whether gene testing for response to warfarin improves outcomes in the NEJM.   Two other studies suggested genetic testing was important for reducing bleeding associated with warfarin but not for new clot busting drugs. 

 When you come up with a conglomerate of conclusions that suggest testing is not necessary for different reasons and medicines it would make sense to suggest that you might want to do testing to get it right.   But all studies conclude that genetic testing is not necessary in most cases. 

 Let’s take a look at the NEJM article that compared bleeding events in patients treated with  warfarin vs placebo to see why that might not be the best clinical approach:

“Results are presented only for patients of European or Latin American ancestry. Patients with other ancestries were excluded because of small numbers (99 patients in the next largest group) and concern about the potential for population stratification.” 

“Only 18.0% of patients in the CURE population included in our study underwent PCI, and only 14.5% underwent PCI with placement of a stent, as compared with more than 70% in previous studies.”

So the study --  truly a one size fits all approach – excludes African Americans and people undergoing PCI

Further:
"Carriers had a more pronounced reduction in cardiovascular events with clopidogrel treatment as compared with placebo than did noncarriers (hazard ratio with clopidogrel among carriers, 0.55; 95% CI, 0.42 to 0.73; hazard ratio among noncarriers, 0.85; 95% CI, 0.68 to 1.05; P=0.02 for the interaction). A similar interaction was observed with respect to the second composite primary outcome (hazard ratio with clopidogrel among carriers, 0.66; 95% CI, 0.54 to 0.82; hazard ratio among noncarriers, 0.90; 95% CI, 0.76 to 1.06; P=0.03 for heterogeneity)."

Isn’t finding out who  benefits more a good reason for testing?   Eric Topol thinks so:

“Genomics expert Dr Eric Topol (Scripps Research Institute, La Jolla, CA) told heartwire: "Both TRITON and PLATO reinforce the CYP2C19 story . . . that loss-of-function variants lead to diminished clinical impact for clopidogrel. PLATO takes this a step further to now show that the gain-of-function allele *17 is associated with more bleeding."

http://www.theheart.org/article/1114619.do

The rush towards headline grabbing instant analysis undermines a more systematic analysis in the Meridia and genetic testing issues and ignores the fact that RCT’s have limitations.

As another editorial noted with respect to gene testing:

“Besides genetic profiles, the evaluation of the best management should also take into account the clinical determinants of platelet reactivity—from age and sex to body-mass index, diabetes, and inflammation—that modulate platelet function, while also considering the timing from the acute event, she adds. "Prospective studies evaluating different antiplatelet treatments tailored according to the individual characteristics of patients are urgently needed to identify therapeutic strategies that will provide the best benefit for the single patient in this high-risk clinical setting."

Too bad CER funding is not available for such research.

A new poll shows that public support for healthcare reform dropped sharply in August. 

The Kaiser Health Tracking Poll has support for the bill dropping 7 percentage points in August — down to 43 percent — while opposition rose 10 points to 45 percent.

Respondents listed healthcare as the third most important factor in deciding how they’ll vote this fall — behind the economy and “dissatisfaction with government.”

Forty-two percent of respondents said healthcare reform will play an “extremely important” role in their ballot-box decisions, on par with the 41 percent who said the same thing in June.

A series of insurance industry reforms, including a ban on lifetime or annual caps on insurance coverage and free preventive care on new insurance plans, have proved popular in polls, but the popularity of the overhaul on the whole hasn’t improved. Plus, opposition to other provisions — namely, the requirement that nearly all Americans buy insurance coverage — has increased. The so-called “individual mandate” was opposed by 70 percent of the Kaiser poll’s respondents.

Take a breath.  Some news about the FDA and comparative effectiveness.  Relax – it’s not what you think (or what the people at Consumer’s Union want).

The new efforts will not affect product approvals and instead focus on simply answering a slew of outstanding questions by leveraging the abundance of collected data stored at the agency.  And it’s about time.  The FDA sits at the nexus of vast amount of untapped and highly important data. And while data is great, knowledge is power. 

The American Recovery and Reinvestment Act (aka, “the stimulus package”), the FDA received funding (via AHRQ) to develop a CER infrastructure with outside assistance.

The agency's multi-step CER approach that includes creating the Janus data repository and developing at least one external center through the Partnership in Applied Comparative Effectiveness Science (PACES) initiative to examine the collected data, assess the information and make recommendations to answer questions on different therapies and patient groups. The data will include information from new product submissions and previously submitted product applications.

In parallel to the creation of the Janus data repository, the agency will also convert legacy data into a standardized format that can be inputted into the system. Agency officials acknowledged that the data retrofit will be costly, and the ARRA funding will focus on piloting the initiative to determine whether the program's benefits outweigh its costs. But that depends, largely, on how the agency chooses to define "benefits" -- and over what period of time?

Instead, she said the program will address the real world impact of therapies, help improve consistency and transparency in the approval process and identify healthcare gaps. For example, the examination of data could identify sub-populations that are not impacted by certain classes of drugs, with those patients potentially obtaining improved health outcomes from different therapies, such as certain devices.

Pulse check – this is not CER as part of the PDUFA process.

Janet Woodcock: "I think the science is still too early to be able to really design comparative trials that stand much chance of being conducted, at least pre-approval.”

Personalized medicine?  Well, yes – if you consider the use of outcomes data to be personalized medicine.  And it is.  It’s certainly an important first step towards realizing the “four rights” (right medicine in the right dose for the right patient at the right time).

FDA Chief Scientist Jesse Goodman: "In the long run for FDA and the sponsors, this will make everything more efficient. … Moving towards identifying what's the right way to do it does take some maturation of technology.”

Oh yes. And to that end the FDA will strive to implement “modern analytical tools” to examine the data. Easier said than done – but it’s money well spent.

In the belief that facts drive guidance and oversight on behalf of the public health, some interesting and important data on attitudes towards risk and benefit in DTC ads.

(Note – key word is “ads” – not social media.)

Attitudes toward Risk/Benefit Info in DTC Ads

TV       Magazine      Online

 Risk

Seen/heard                                            79%         48%              37%

Seen/heard                                           73%           52%              54%

Pay a lot/some attention                        63%           63%              57%

With “utility” almost even across the board (76%/75%/75%), it’s the risk stats that give pause for reflection. 

While 79% have “seen/heard” risk information on TV ads (not surprising since the viewer passively receives it whether they want to or not), and print (48%) out-strips online (37%). 

But the race tightens in the “pays a lot/some attention" – where TV still leads (we are, after all, glued to the couch), but online (69%) out paces print (66%).  Among other conclusions, this points to (1) the well-documented inadequacies of the brief summary (i.e., neither brief nor a summary) and (2) the greater desire of the online ad viewer to click to risk information.  Put another way –nearly 70% of online ad viewers actively click-through to risk information.  Pretty impressive – and even more so considering this data was collected well after the November 2009 FDA letters on sponsored Google links.

Food for thought.

Suddenly end-of-life care is back in vogue.

Here’s the New York Times explaining why: 

In a study that sheds new light on the effects of end-of-life care, doctors have found that patients with terminal lung cancer who began receiving palliative care immediately upon diagnosis not only were happier, more mobile and in less pain as the end neared — but they also lived nearly three months longer.

The findings, published online Wednesday by The New England Journal of Medicine, confirmed what palliative care specialists had long suspected. The study also, experts said, cast doubt on the decision to strike end-of-life provisions from the health care overhaul passed last year.

“It shows that palliative care is the opposite of all that rhetoric about ‘death panels,’ ” said Dr. Diane E. Meier, director of the Center to Advance Palliative Care at Mount Sinai School of Medicine and co-author of an editorial in the journal accompanying the study. “It’s not about killing Granny; it’s about keeping Granny alive as long as possible — with the best quality of life.”

 
Here’s what the study found and what the New York Times conveniently ignores: People with end stage lung cancer who were given palliative care at diagnosis and  simultaneously with standard cancer care  “had a significantly better quality of life and significantly lower rates of depression than those who received only standard care.

They also lived longer — median survival for patients in the simultaneous-care group was 11.6 months and in the standard-care group was 8.9 months (P = .02). This survival benefit of 2.7 months is similar to that achieved with standard chemotherapy regimens.”  (www.nejm.org)

The New York Times  reporting makes it seem that palliative care alone was better and that it was therefore wrong to eliminate end of life counseling from Obamacare by calling it a death panel.

In fact, end of life counseling in the original version of Obamacare was not about  “keeping Granny alive longer” or even palliative care.

Section 1233 of the health-care bill drafted would have paid doctors to give Medicare patients end-of-life counseling “every five years -- or sooner if the patient gets a terminal diagnosis.” 

And the counseling was to include advanced care planning, including key questions and considerations, important steps, and suggested people to talk to about” living wills and durable powers of attorney, and their uses …a list of national and State-specific resources to assist consumers and their families."   Not a word about living longer. To suggest now that’s what Democrats meant is absurd: If spending more money to let Granny live longer after a terminal diagnosis  why keep reminding people every five years about “living wills”?

Because it’s a way of telling seniors as they get older that living longer is not very valuable.  Here’s Victor Fuchs, an Obamacare advocate, economist and long time consultant to Donald Berwick and Obama’s health policy adviser Ezekiel Emanuel on technologies that extend life:

“..further gains in life expectancy will mostly mean keeping more Americans alive while they are retired and dependent on indirect transfers of funds from younger workers for much of their living expenses, health care, and social services.”   Because keeping people alive longer is so…wasteful Fuchs suggests government discourage “ innovations that increase life expectancy”  in favor of innovations, such as joint replacement, that improve the quality of life for both the elderly and the near-elderly.”

This is ideology masquerading as science.  In fact, advances that improve quality of life also tend to improve survival especially when it comes to diseases associated with aging.  And it winds up reducing or slowing the cost of treatment.   Since 1996, the average per patient costs for cancer, heart disease and mental illness have declined in inflation adjusted dollars.  And life expectancy continues to increase as well. 

But that’s not good enough for Fuchs,Berwick and others.   And just because of end of life counseling is gone, Obamacare has other tools to shorten life.  One way to do it is to have the government not pay for any new technology that doesn’t meet this goal.  Another is to not count spending on such innovations when determining if a health plan spent the federally required 80-85 percent of it’s premiums on medical care.   Still another is paying doctors to discourage people from using new technologies by discussing their risks and lack of value.   

Fuchs states: Obamacare should only pay for   “innovations whose main effect is to substantially decrease cost while holding quality constant or reducing it only slightly.”   Many Obamacare advocates endorse his view with enthusiasm.  Yet by that standard, a combination of palliative and standard care that increases well-being and extends lives would be discouraged by government.   Maybe the term “death panel” understates the problem.

From the pages of the Wall Street Journal:

By Katherine Hobson

consumers who were skeptical.

Cleveland Plain Dealer reported yesterday. In response to a question after a speech, Toby Cosgrove said he wanted to ensure that manufacturers and investors would still be willing to make financial bets on unproven devices and drugs. He used the example of a heart valve, saying it now takes two decades to bring a new valve product to market and then assess the effectiveness.

(Cosgrove knows of which he speaks; his bio says he has 30 patents filed, including heart valves and surgical instruments.)

might present some tough obstacles for cancer research.

If we learn nothing else from BP’s recent unpleasantness, it’s that being able to identify an obvious problem (like when oil is gushing uncontrolled into the Gulf of Mexico) is one thing.  Identifying that there is a potential problem is tougher.  And toughest of all is designing a solution that addresses a need early in the curve.

Case in point, Alzheimer’s Disease. As Gina Kolata writes in today’s New York Times, “The failure of a promising Alzheimer’s drug in clinical trials highlights the gap between diagnosis — where real progress has recently been made — and treatment of the disease.”

Alzheimer’s Disease is a healthcare oil spill of draconian proportion.

Recent significant steps forward in early diagnosis of the disease are important.  And frustrating -- because there is still precious little that can be done when this devastating condition is identified either late in the game or in its nascent stages. 

To say that the science is “hard” (while true) is not particularly helpful.  What needs to be addressed are the twin issues of drug development and regulatory science.  Both are lagging.  Biomarkers notwithstanding, more needs to be done.  We need better tools.  Too many programs  (almost 50%) are failing in late Phase III. Too many programs are mired in regulatory treacle.  The economics are unsustainable from a corporate R&D standpoint and the impact of Alzheimer’s Disease on patients, their families and American healthcare economics is devastating.

Better, more current and predictable scientific research and standards must be developed and devoted to streamlining the critical path. Investment in basic research is not enough. Specifically new development tools are needed to improve the predictability of the drug development cycle and to lower the cost of research by helping industry identify product failures earlier in the clinical trials process.