Latest Drugwonks' Blog
First it is important to know what’s in JANUS and what is not:
“The JANUS warehouse was populated with sample synthesized human trial data related to two oncology studies. This data was furnished in standard STDM format and data load scripts were developed to import the data. A sample caCORE application was developed to demonstrate the analytical capabilities of such an application accessing the underlying JANUS repository. The application was modeled against SDTM domain views of the Janus warehouse instead of the warehouse schema itself to alleviate complexity and improve data access efficiency. The sample application was successful in that you could authenticate the users at signon using CSM authentication and then review the clinical trial data in the following ways:
- View patient enrollment by study
- View patient retention by study
- Efficacy reporting by study
- Safety reporting by study
Note the absence of genomic data.
· Conduct a review of a sample of FDA clinical trials performed to assess drugs, biologics and devices. This review shall include clinical trial data used in pre-market submissions for one class of drugs or devices.
· Evaluate comparator groups, populations studied, study designs, endpoints, statistical analysis methods, and trial conduct.
· Include an evaluation of the capability of each study to distinguish differences in effectiveness and safety among different populations, subpopulations and individuals.
· Provide formal recommendations for best practices for submission of studies to the FDA when they involve product comparisons.
While a long term goal of analyzing JANUS data is identify robust data standards to capture and exchange clinical genomic data, that goal is not addressed or funded.
Most troubling is that the vendors interested in submitting bids lack any expertise in achieving this goa.l Many of them are superb and innovative providers of infrasture or developers of portals for delivering clinical data. But the only vendor that is in the business of analyzing data has significant conflicts of interest in my opinion. And that’s The Center for Medical Technology policy run by Sean Tunis. When Tunis left Medicare in 2005 and set up the Center, the Agency for Healthcare Quality and Research was his first client. Tunis also served on the Institute of Medicine panel that set the CER agenda for the Federal Coordinating Council on Comparative Effectiveness Research of which FDA is a part.
Moreover, Tunis has a distinct bias against using any new technology absent the kind of evidence he believes is important. Consider his self-serving white paper on how Designing More Informative Clinical Trials for Off-Label Uses of Oncology Drugs which has the goal of establishing CMT as the entity that will create standards and conduct studies using clinical data to compare a standard treatment to a newer use. Tunis wants payors to require such studies before reimbursement is made. And since CMT would be the standard setter, guess who would get all the CER business?
Tunis makes the same lame claim all CER advocates and contractors use:
“Despite the prevalence of off-label use of oncology drugs and related services, the health outcomes and value of expenditures on these products and services are not well
understood.”
“Off-label oncology CERs should be designed to be generalizable in that they include sociodemographic diverse patient populations as well as patients with common comorbidities that exist among cancer patients and/or are positively or negatively associated with the use of oncology drug.”
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.
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.
