Latest Drugwonks' Blog
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).
By the end of September, the FDA will launch several initiatives to aggregate data on medical products, assess the information and eventually answer a myriad of questions on patient populations and class-wide issues, according to agency officials.
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.
The Janus data repository will serve as the crux of the program and a "hub" that aggregates a substantial portion of collected agency information. One of the FDA officials described the data aggregation design as a "federated model" that will take advantage of the wealth of agency data collected for decades.
The data will come from standardized electronic product applications, previously submitted products, the Sentinel post-market analysis system, the MedWatch program, the common electronic document room, the automated laboratory management system and other data sources, officials said.
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.
The program will not aggregate data on unapproved drugs, and only focus on new submissions and retrofitting information from approved products that were previously introduced on the market.
It’s a smart move. The more information the agency has on both individual and class MOAs the better it can understand how things work in the real world (beyond the neatly designed, gold standard world of RCTs).
FDA science adviser Vicki Seyfert-Margolis said the program is not focused on directing regulatory actions, restricting randomized controlled clinical trials or limiting access to healthcare services.
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.”
According to FDA Week, “Agency sources said the Janus data repository and the PACES centers are not intended for use in making product-specific decisions in the premarket arena, and instead will simply enable the agency to understand the science behind certain classes of drugs, how they compare to other treatment options in patient subpopulations and assess the effect of genetics on therapies.” This is about personalized medicine [which is] a major new area of investment," an agency official stressed. "We're not using this to do cost assessments."
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).
The FDA will not release product-specific data from this initiative to the public, but the agency hopes to publish information on general CER methods and strategies developed through the PACES program. The agency could also (and should) release answers to questions on the impact of genetics on certain therapies and class-wide observations.
How does this relate to the Critical Path initiative?
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.
"Bad science conducted to support litigation."
Via the AP -- and without mincing words ...
A federal appeals court on Friday upheld a ruling that vaccines are not to blame for autism.
The U.S. Court of Appeals for the Federal Circuit upheld a decision last year by a special vaccine court, which concluded there's little if any evidence to support claims of a vaccine-autism link.
Scientist years ago reached that conclusion, but more than 5,500 families sought compensation through the government's Vaccine Injury Compensation Program.
Friday's ruling came in the case of Michelle Cedillo of Yuma, Ariz., who is disabled with autism, inflammatory bowel disease and other disorders that her parents blame on a measles vaccine given at 15 months.
In the 2009 ruling Special Master Denise Vowell wrote that the evidence "is weak, contradictory and unpersuasive. Sadly, the petitioners in this litigation have been the victims of bad science conducted to support litigation rather than to advance medical and scientific understanding" of autism.
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.
TV Magazine Online
Seen/heard 79% 48% 37%
Pay a lot/some attention 76% 66% 69%
Say it is very/somewhat useful 76% 75% 75%
Benefits
Seen/heard 73% 52% 54%
Say it is very/somewhat useful 75% 76% 76%
Source: Rodale, "2010 DTC Study," July 15, 2010
What does this tell us? Well, on the “benefit” side, it seems to suggest that consumers rank all three media equally when it comes to utility (“say it is very/somewhat useful”). And while TV and print still seem to have an edge in the “pay a lot/some attention” department (at 63%), online ads are a very close show at 57%. Decimal dust? Not when you’re doing ROI calculations -- but it’s really only a half-game lead – and the momentum is shifting online's way.
In the “seen/heard” department, TV leads both print and online – but online beats print – further adding to the “death of print” argument.
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%).
Hello Muddah. Hello Faddah.
A new study in the August issue of the Journal of Applied Communication Research (conducted by researchers at the Universities of Pennsylvania and Georgia) shows that direct-to-consumer ads that make mention of family history as a significant risk factor for a disease resonates strongly with their target audiences.
Those who viewed the ads indicated a stronger intent to adopt healthy behaviors as well as a stronger intent to seek the medications that were advertised. The researchers concluded consumers were willing to mix pharmaceutical and behavioral changes to minimize their risks to diseases that could be related to genetics.
The study involved a group of 395 adults who viewed four magazine ads, including three for drugs: Bayer aspirin for heart disease, Vytorin (ezetimibe/simvastatin) for high cholesterol, and Actonel (risedronate sodium) for osteoporosis. The fourth was a "masking" ad for ThermaCare , an over-the-counter product for joint and muscle pain.
All participants who saw the ads with familial risk cues, regardless of the level of family disease history, showed a strong intent to purchase medications. The results also indicated that that the consumers who saw the ads with familial risk cues had stronger intentions to engage in healthy lifestyles than those who did not.
"Exposure to familial risk cues in DTC prescription drug ads enhanced behavioral intentions for both healthy lifestyles and for pharmaceutical choices," the article states.
Only in AARP's real world.
Retail prices for some of the most widely used brand-name prescription drugs shot up more than 8 percent in 2009, even as inflation plummeted to a record low, according to a new AARP analysis of retail drug price trends released today. The AARP Rx Price Watch Report also looked at retail drug prices over the past five years and found some huge increases for popular drugs including the prostate drug Flomax, which nearly doubled in price; Advair and Aricept saw price hikes of 40 percent. During the same period, the consumer price index rose 13.3 percent. The findings show that the cost of prescription drugs—many widely used by those on Medicare—far outstripped the price increases for other consumer goods and services. … The AARP report found that all but six of 217 brand-name prescription drugs had retail price increases exceeding general inflation last year.
Conducted by long time pharma-price schlockmeister, Stephen Schodelmeyer, the "study" ignores the fact that the 217 brand name drugs were actually a smaller number of medications with different doses and that for most, if not all of the drugs, there was a generic alternative. It also ignores the fact that almost no one pays retail or the full cost of a medication or that the retail price includes drugstore mark ups..
Meanwhile, another reliable survey, this from Consumers Union, claimed that 27 percent of people skipped or split medications to save money. Then again, up to half of people who actually have drug coverage skip or stop taking medications. Did Consumers Union consider other reasons than money?
And by the way, it's survey showed that "a whopping 81 percent said they are concerned about the rewards drugmakers give to doctors who write a lot of prescriptions for a company’s drugs. And 72 percent were displeased with payments pharmaceutical companies give to doctors for testimonials or for serving as a company spokesperson for a given drug."
Rewards? Do they mean the pens or the calendars? And how much of a drug do you have prescribe to get such a nifty prize. You see, that's what passes for rewards these days since companies no longer hand out bags of jewelry and cash.
The coverage of these studies in the media was free of any analysis or context. Instead the journalists simply rewrote the press releases of the two organizations and linked to them in blogs... (You can read about both in the Kaiser Healtn News service which also substitutes for health care reporting in major newspapers around the country.)
Way to go.
www.kaiserhealthnews.org/Daily-Reports/2010/August/26/Drug-prices.aspx
In a 33-page opinion, Judge Emmet Sullivan of U.S. District Court in Washington, D.C., declined to issue a preliminary injunction blocking the sales of the generic Lovenox.
sanofi-aventis sued the FDA after the agency granted Sandoz approval to make enoxaparin (the generic form of the special heparin).
s-a contended that the FDA didn’t follow its own regulations in granting the approval. s-a, interestingly, didn’t claim that the Sandoz product was unsafe. Rather, they argued that the enoxaparin made by Sandoz is not exactly the same drug as Lovenox and therefore should not be approved or marketed as a copycat version of the blockbuster.
But has anyone ever argued that either traditional Hatch-Waxman generics or FOBS need to be 100% bioequivalent? Indeed, is that even possible? No and no. It is equivalence of functionality based on activity. The generic or the FOB has to work the same way and be designed in ways that produce such functional equivalence. But that doesn’t mean that interchangeability in prescribing is always appropriate. That, however, isn’t a legal matter. It’s a therapeutic one.
Judge Sullivan ruled that the FDA had not acted inappropriately in approving enoxaparin. "Just because the FDA … reached a conclusion at odds with the position advanced by Sanofi does not mean that the FDA's decision was arbitrary and capricious," he said, noting that it has been seven years since s-a filed a citizen's petition at the FDA objecting to generic versions of Lovenox.
He said, the FDA had presented "a satisfactory explanation for its decision." Judge Sullivan noted that none of the parties had challenged the safety of the generic enoxaparin.
And that’s the best victory for both the FDA and the public health.
For more on the issue, see here.
Yesterday the FDA released a preliminary draft of the restaurant menu labeling rules that will go into effect on March 23, 2011. A section of the health care legislation passed in March mandates that restaurants clearly display calorie information on menus, including sit down and drive through menus.
The draft guidelines can be found
Here’s the New York Times explaining why:
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.”
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.
According to three new studies in the latest issue of the American Journal of Hypertension, almost half of the 50 million Americans with hypertension haven't been prescribed the drug that would work best for them.
"Our current prescribing methods are very primitive. We haven't increased the success rate [in treating hypertension] in 35 years," says Michael Alderman, a blood-pressure expert at the Albert Einstein College of Medicine in New York City, and a co-author of one of the new studies.
One study shows some drugs work better in certain ethnic groups than in others. The two other studies recognize the importance of testing patients' levels of renin, a hormone produced by the kidneys, as a guide in prescribing blood-pressure medicine. Researchers in each of the studies emphasized that larger-scale trials would be necessary before the findings could become part of official treatment guidelines.
Welcome to what “personalized medicine” really means. Not “bespoke” or tailored medicines, but rather a focus on the “four rights” – the right medicine in the right dose for the right patient at the right time.
One of the studies, co-authored by Ajay Gupta of Imperial College London, looked at drug responses among 5,425 patients in various countries and across different ethnic groups. For example, in the U.K., south Asians are often given ace inhibitors as a first-line treatment, though the effectiveness of such prescriptions isn't based on any hard evidence. Dr. Gupta's study, for the first time, confirms that south Asians respond especially well to such drugs.
U.K. medical-treatment guidelines say that first-line drug therapies should be guided by a patient's age and race. (Guidelines in the U.S. don't include such suggestions – but since we’re looking at the NHS to learn about comparative effectiveness, maybe we should broaden our field of study, especially considering that our new CMS chief is such a fan of the UK model.)
And, while we're on the subject of the NHS, a brief digression. Did you see today's news that NICE has rejected Avastin for use in patients with colerectal cancer that has spread? It's the second time that the agency has issued such guidance. At the same time, NICE Chairman Sir Michael Rawlins has suggested that the best way to counteract the dearth of real science behind HTA is for drug companies to just lower their prices. Sir Michael is a bright guy and needs to do better than such a simplistic answer to the problem of 21st century HTA's lack of scientific integrity.
The two other studies focused on the hormone renin. Medical experts say few doctors today measure a patient's renin level, despite a study in the 1970s that suggested it might be used as a biomarker for prescribing the drugs. One of the new studies, involving 363 patients, confirmed the 1970s finding, showing that measuring the renin level can be an effective method for selecting a blood-pressure medication.
"These are not fundamentally novel biological discoveries," says Morris Brown, professor of clinical pharmacology at the University of Cambridge, U.K., who wasn't involved in the studies. But they constitute "a wake-up call that we should be using renin measurements as a systematic form of help" for prescribing hypertension drugs.
And it should also serve as a wake-up call to those who aren't paying close enough attention to the future of diagnostics development and approval.
Center for Medicine in the Public Interest is a nonprofit, non-partisan organization promoting innovative solutions that advance medical progress, reduce health disparities, extend life and make health care more affordable, preventive and patient-centered. CMPI also provides the public, policymakers and the media a reliable source of independent scientific analysis on issues ranging from personalized medicine, food and drug safety, health care reform and comparative effectiveness.
