Latest Drugwonks' Blog
Dear CDER Staff:
On September 6, 2012, CDER Center Director Janet Woodcock informed you that she would be proposing important organizational changes within the Center to sharpen the Center’s focus and strengthen resources around pharmaceutical quality.
As part of these organizational changes, we will also be proposing that the Drug Shortages Staff (DSS) be moved from the Office of New Drugs and be elevated to the Office of the Center Director under the leadership of Deputy Director for Regulatory Programs, Dr. Doug Throckmorton.
On July 9, 2012, President Obama signed into law the Food and Drug Administration Safety and Innovation Act (FDASIA) of 2012. In this new law, Congress provided FDA with new authorities to combat shortages of drug products in the United States and imposed new requirements on manufacturers regarding early notification to FDA of issues that could lead to a potential shortage or disruption in supply of a product.
Drug shortages can occur for many reasons, including manufacturing and quality problems, delays, and discontinuations. They have reached crisis proportions for many healthcare systems and are creating personal crises for many patients. Fortunately, the Agency has been able to prevent a significant number of drug shortages. In 2011, FDA helped prevent 195 drug shortages; as of August 2012, FDA prevented close to 100 shortages.
FDA places tremendous value on the Center’s efforts to curb drug shortages. In addition, with the new authorities brought by FDASIA, we look forward to an ever-increasing focus on this crucial program.
The proposed elevated placement for DSS -- with its greater visibility and prominence within the Center -- reflects how important the work of the DSS is to ensuring that patients in need have critical and life-saving drugs available to them. Undoubtedly, this work is paramount to the Center’s mission to guarantee that safe, effective, and high-quality drugs are available to the American public.
Doug Throckmorton
Deputy Director for Regulatory Programs, Office of the Center Director
John Jenkins
Director, Office of New Drugs
Each year, physicians in America conduct over 1.2 billion patient visits, treating illnesses ranging from the minor to the life-threatening.
With A Survey of America’s Physicians, the Physicians Foundation has endeavored to provide a “state of the union” of the medical profession. What are physicians thinking about in the year 2012: about the practice of medicine, about their career plans, and about the current state of the healthcare system?
The survey was sent to over 630,000 physicians – or over 80 percent of physicians in active patient. One thing is clear -- it is a challenging and uncertain time to be a doctor.
The results of the survey reflect uncertainty and should be taken in the context of current events.
Key findings include:
* Over three quarters of physicians – 77.4 percent – are somewhat pessimistic or very pessimistic about the future of the medical profession.
* Over 84 percent of physicians agree that the medical profession is in decline.
* The majority of physicians – 57.9 percent -- would not recommend medicine as a career to their children or other young people.
* Over one third of physicians would not choose medicine if they had their careers to do over.
* Over 52 percent of physicians have limited the access Medicare patients have to their practices or are planning to do so.
* Over 26 percent of physicians have closed their practices to Medicaid patients.
* Over 62 percent of physicians said Accountable Care Organizations (ACOs) are either unlikely to increase healthcare quality and decrease costs or that that any quality/cost gains will not be worth the effort.
* Over 59 percent of physicians indicate passage of the Patient Protection and Affordable Care Act (i.e., “health reform”) has made them less positive about the future of healthcare in America.
What’s wrong with this picture?
The complete study can be found here.
A companion’s words of persuasion are effective.
-- Homer
Diagnostic test quality may not be something that pharmaceutical and biotechnology companies have had a lot of experience dealing with, but shortfalls in a diagnostic development program can undercut efforts to streamline clinical trials for personalized medicines.
The Pink Sheet reports that the need for a high-quality diagnostic test development program was a key message delivered by a representative from FDA’s devices center at a September 14th conference on drug/diagnostic co-development.
The conference, sponsored by the Friends of Cancer Research and Alexandria Real Estate Equities Inc., served as a discussion forum for a multi-stakeholder draft proposal aimed at enabling late-stage clinical development of drugs with companion diagnostics by quickly identifying a patient subset most likely to benefit from treatment while minimizing exposure of patients least likely to benefit.
FDA officials were generally receptive to the draft ideas put forward. However, they highlighted the threshold need for a well-characterized, high-quality diagnostic that can accurately distinguish between those patients well-suited for treatment and those unlikely to derive any benefit.
The draft conference paper presented at the meeting was developed with the goal of guiding design of Phase III trials to evaluate a drug and companion diagnostic in situations where prior studies do not provide a clear definition of the diagnostically selected population and sufficient evidence to restrict development.
The draft is intended to fill some of the stakeholder-identified gaps in FDA’s July 2011 draft guidance on vitro companion diagnostic devices. In that 12-page guidance, FDA explained how it defines a companion diagnostic and its expectations for simultaneous development and approval of a drug with the accompanying test.
However, the guidance left many in the drug and device industries wanting more details, such as the regulatory ramifications for drug/diagnostic combinations that are not developed and reviewed in parallel fashion and how laboratory-developed tests fit into the agency’s paradigm for companion diagnostics.
“Patients have to be protected by appropriately balancing the strength of the diagnostic hypothesis with the need for thorough data generation and evaluation,” the draft paper states. “We believe the appropriateness of including marker-negative patients primarily depends on the strength of the science in support of the diagnostic hypothesis (including but not limited to mechanism of action, pre‐clinical efficacy and, if known, class effect), the potential for risk to patients, and clinical data available to date,” the draft paper states.
FDA Office of Hematology and Oncology Products Director Richard Pazdur highlighted several basic principles that FDA considers when evaluating the use of biomarkers in applications submitted to the agency.
The first among these is that the companion diagnostic must be essential for use of the drug, Pazdur said. “It’s not like we’d like to have it or it might be nice to have it or we might in the future need it. It should be essential for the use of the drug when it is licensed.”
The U.S. should implement policies that will double the output of new, innovative medicines for important unmet medical needs within 15 years, according to a report released yesterday by the President's Council of Advisors on Science and Technology. The report on "Propelling Innovation in Drug Discovery, Development, and Evaluation" said this goal could be met through increasing funding for basic, translational and regulatory science and creating a broad-based partnership bringing together government, industry, academia and other stakeholders to improve the discovery, development and evaluation of new medicines.
The report recommends creating a new "special medical use" pathway to approve drugs for narrow populations. It also recommends strengthening FDA's postmarketing surveillance capacity by appropriating $40 million per year for the agency's Sentinel electronic safety surveillance system. PCAST said FDA should explore the creation of an adaptive, or progressive, approval system, but it concluded that legislation creating an adaptive approval system "would be premature at this time."
The Patient-Centered Outcomes Research Institute’s draft methodology report contains discussions and language choices that could (per Pink Sheet reportage) “tarnish” the institute’s approach to research on pharmaceuticals.
Rust never sleeps.
Both PhRMA and BIO express consternation about what they see as the draft report’s implication that the public should be suspicious of the results of drug industry-sponsored trials.
Their views are contained in recent comments on a draft methodology report written by PCORI’s Methodology Committee. The methodological standards contained in the report will be part of funding review criteria for future applicants for the institute’s research grants.
The idea that manufacturer-sponsored trials may be untrustworthy is mentioned in the report’s introductory chapter, which contains a section labeled “A trust problem.”
PhRMA, in its written comments, responds that the “implication that physicians are willing to subject patients to potential harm as a result of financial interests is troubling and should be deleted.”
BIO’s written comments agree that the passage is “unduly biased against industry-sponsored research” and “presents a skewed view of research conducted by biopharmaceutical companies.”
The Association of Clinical Research Organizations takes an even stronger stance, saying that for the Methodology Committee “to make such assertions of manipulation or bias without any supporting evidence is highly problematic and calls into question the objectivity and integrity of the committee.” It adds that the discussion “impinges on PCORI’s credibility as a research organization by exposing its own potential bias.”
And then there’s the issue of cost in the draft report’s Chapter Five. It says: “The committee’s view is that in the context of PCOR, cost, like other aspects of the health care delivery system, can be a factor in the effectiveness of care if it influences choices made by patients and clinicians. Cost can be an incentive for delivering inappropriate care, not just a barrier to appropriate care. Providers may have incentive to favor more costly treatments under the common belief that ‘more is better’ in healthcare.”
BIO contends that identifying cost as a potential endpoint “is in direct conflict with the authorizing statute’s specific prohibition of PCORI from considering cost effectiveness in studies of comparative effectiveness.”
PhRMA asserts, “While cost undoubtedly can influence the quality and patient-centeredness of care that individuals receive, research that includes cost as an element of analysis or endpoint of measurement is outside the scope of PCORI’s mandate.”
Industry commenters also say the report is trying to do too much by addressing issues that lie outside of research methodology, in particular the report’s discussions of setting research priorities – the topic of an entire chapter – and disseminating research results.
BIO observes that ACA assigns two responsibilities to the methodology report: provide recommendations for PCORI on methodological standards and develop a translation table to guide researchers in applying the standards to specific studies. The “diversity of other subjects the report discusses,” in particular the discussions of the dissemination of research results and developing research priorities, “distracts from the mandated focus on scientifically-derived methodological standards for PCOR and the framework underpinning the development of a translation table,” BIO says.
PhRMA joins in calling for PCORI to cut these non-mandated subjects from the report, saying that given the resources demands of providing comprehensive standards for PCOR, “we recommend PCORI focus its report on standards for research, rather than important but ancillary issues like research priority-setting and results dissemination.”
Studies more firmly tie sugary drinks to obesity
By MARILYNN MARCHIONE - AP Chief Medical Writer - Associated PressFriday, September 21, 2012
New research powerfully strengthens the case against soda and other sugary drinks as culprits in the obesity epidemic.
A huge, decades-long study involving more than 33,000 Americans has yielded the first clear proof that drinking sugary beverages interacts with genes that affect weight, amplifying a person's risk of obesity beyond what it would be from heredity alone...
This means that such drinks are especially harmful to people with genes that predispose them to weight gain. And most of us have at least some of these genes.
In addition, two other major experiments have found that giving children and teens calorie-free alternatives to the sugary drinks they usually consume leads to less weight gain.
Collectively, the results strongly suggest that sugary drinks cause people to pack on the pounds, independent of other unhealthy behavior such as overeating and getting too little exercise, scientists say.
That adds weight to the push for taxes, portion limits like the one just adopted in New York City, and other policies to curb consumption of soda, juice drinks and sports beverages sweetened with sugar.
Now what's wrong with the article and the studies that make this claim?
1. The article on genetics and soft drinks did not control for other forms of sugar or interaction with other behaviors. Or other genes for that matter. For instance, there are other genetic mutations that appear regulate obesity which interact with the amount of fiber in one's diet.
2. Even if gene-soft drink association (let's just say sugar) is established, the contribution of the genetic factor may be -- and has been reported to be -- quite small. For instance, most of us have genetic mutations that increase the risk of diabetes or cancer. But the relative contribution of those genes and their mutations to winding up with either disease is very, very small in most of us. Other factors and genetic interactions trigger disease and influence it's progression. Getting a virus or infection, or having high levels of inflammation, etc. can lead to epigenetic changes that shape disease risk. Shame on the report and the researchers for not qualifying their message in this way.
3. Similarly, the reporter asserts that sugary drinks are the biggest source of calories in the American diet. Wrong. The USDA's Dietary Guideline Advisory Committee gives the breakdown for most Americans...
Yeast breads (129 calories per day)
• Chicken and chicken mixed dishes (121 calories per day)
• Soda/energy/sports drinks (114 calories per day)
• Pizza (98 calories per day)
Soft drinks are not even the biggest source of sugar among many age groups. (Snacks are) Nor are they problem. What is? We don't eat enough plant-based fiber, we take in too much saturated fat.. And we don't exercise. The DGAC again:
Several distinct dietary patterns are associated with health benefits, including lower blood
pressure and a reduced risk of CVD and total mortality. A common feature of these diets is an
emphasis on plant foods. Fiber intake is high and saturated fat is typically low. When
total fat intake is high, that is, more than 30 percent of calories, the predominant fats are
monounsaturated and polyunsaturated fats. Carbohydrate intake is typically in the range of 50 to 60
percent of calories, but these often include whole grain products with minimal processing, as well as
cooked dry beans and peas. The totality of evidence documenting a beneficial impact of plant-based
dietary patterns on CVD risk is remarkable and worthy of recommendation.
The so-called 'empty' calories don't come from soft drinks but the food we eat with them. But soft drinks are a sweeter target and feed into the narrative that corporations process food to kill us for the sake of profits. The same capitalism = pollution story that has been applied to energy, chemicals and pharmaceuticals is being applied to food.
When you think about it, the professional critics and their recording secretaries (the media) are attacking the four human innovations that have made life on t his planet better and healthier.
Study Divides Breast Cancer Into Four Distinct Types
By GINA KOLATA
In findings that are fundamentally reshaping the scientific understanding of breast cancer, researchers have identified four genetically distinct types of the cancer. And within those types, they found hallmark genetic changes that are driving many cancers.
These discoveries, published online on Sunday in the journal Nature, are expected to lead to new treatments with drugs already approved for cancers in other parts of the body and new ideas for more precise treatments aimed at genetic aberrations that now have no known treatment.
The study is the first comprehensive genetic analysis of breast cancer, which kills more than 35,000 women a year in the United States. The new paper, and several smaller recent studies, are electrifying the field.
“This is the road map for how we might cure breast cancer in the future,” said Dr. Matthew Ellis of Washington University, a researcher for the study.
Researchers and patient advocates caution that it will still take years to translate the new insights into transformative new treatments. Even within the four major types of breast cancer, individual tumors appear to be driven by their own sets of genetic changes. A wide variety of drugs will most likely need to be developed to tailor medicines to individual tumors.
“There are a lot of steps that turn basic science into clinically meaningful results,” said Karuna Jaggar, executive director of Breast Cancer Action, an advocacy group. “It is the ‘stay tuned’ story.”
The study is part of a large federal project, the Cancer Genome Atlas, to build maps of genetic changes in common cancers. Reports on similar studies of lung and colon cancer have been published recently. The breast cancer study was based on an analysis of tumors from 825 patients.
“There has never been a breast cancer genomics project on this scale,” said the atlas’s program director, Brad Ozenberger of the National Institutes of Health.
The investigators identified at least 40 genetic alterations that might be attacked by drugs. Many of them are already being developed for other types of cancer that have the same mutations. “We now have a good view of what goes wrong in breast cancer,” said Joe Gray, a genetic expert at Oregon Health & Science University, who was not involved in the study. “We haven’t had that before.”
The study focused on the most common types of breast cancer that are thought to arise in the milk duct. It concentrated on early breast cancers that had not yet spread to other parts of the body in order to find genetic changes that could be attacked, stopping a cancer before it metastasized.
The study’s biggest surprise involved a particularly deadly breast cancer whose tumor cells resemble basal cells of the skin and sweat glands, which are in the deepest layer of the skin. These breast cells form a scaffolding for milk duct cells. This type of cancer is often called triple negative and accounts for a small percentage of breast cancer.
But researchers found that this cancer was entirely different from the other types of breast cancer and much more resembles ovarian cancer and a type of lung cancer.
“It’s incredible,” said Dr. James Ingle of the Mayo Clinic, one of the study’s 348 authors, of the ovarian cancer connection. “It raises the possibility that there may be a common cause.”
There are immediate therapeutic implications. The study gives a biologic reason to try some routine treatments for ovarian cancer instead of a common class of drugs used in breast cancer known as anthracyclines. Anthracyclines, Dr. Ellis said, “are the drugs most breast cancer patients dread because they are associated with heart damage and leukemia.”
A new type of drug, PARP inhibitors, that seems to help squelch ovarian cancers, should also be tried in basal-like breast cancer, Dr. Ellis said.
Basal-like cancers are most prevalent in younger women, in African-Americans and in women with breast cancer genes BRCA1 and BRCA2.
Two other types of breast cancer, accounting for most cases of the disease, arise from the luminal cells that line milk ducts. These cancers have proteins on their surfaces that grab estrogen, fueling their growth. Just about everyone with estrogen-fueled cancer gets the same treatment. Some do well. Others do not.
The genetic analysis divided these cancers into two distinct types. Patients with luminal A cancer had good prognoses while those with luminal B did not, suggesting that perhaps patients with the first kind of tumor might do well with just hormonal therapy to block estrogen from spurring their cancers while those with the second kind might do better with chemotherapy in addition to hormonal therapy.
In some cases, genetic aberrations were so strongly associated with one or the other luminal subtype that they appeared to be the actual cause of the cancer, said Dr. Charles Perou of the University of North Carolina, who is the lead author of the study. And he called that “a stunning finding.”
“We are really getting at the roots of these cancers,” he said.
After basal-like cancers, and luminal A and B cancers, the fourth type of breast cancer is what the researchers called HER2-enriched. Breast cancers often have extra copies of a gene, HER2, that drives their growth. A drug, Herceptin, can block the gene and has changed the prognosis for these patients from one of the worst in breast cancer to one of the best.
Yet although Herceptin is approved for every breast cancer patient whose tumor makes too much HER2, the new analysis finds that not all of these tumors are alike. The HER2-enriched should respond readily to Herceptin; the other type might not.
The only way to know is to do a clinical trial, and one is already being planned. Herceptin is expensive and can occasionally damage the heart. “We absolutely only want to give it to patients who can benefit,” Dr. Perou said.
For now, despite the tantalizing possibilities, patients will have to wait for clinical trials to see whether drugs that block the genetic aberrations can stop the cancers. And it could be a vast undertaking to get all the drug testing done. Because there are so many different ways a breast cancer cell can go awry, there may have to be dozens of drug studies, each focusing on a different genetic change.
One of Dr. Ellis’s patients, Elizabeth Stark, 48, has a basal-type breast cancer. She has gone through three rounds of chemotherapy, surgery and radiation over the past four years. Her disease is stable now and Dr. Stark, a biochemist at Pfizer, says she knows it will take time for the explosion of genetic data to produce new treatments that might help her.
“In 10 years it will be different,” she said, adding emphatically, “I know I will be here in 10 years.”
A research letter published in JAMA says “closer attention” should be paid to the lack of risk information in advertising for the OTC switch versions of prescription drugs. Research sponsor CVS Caremark says OTC ads should convey the same information as Rx ads.
Facts are facts – Drug Facts, to be precise. And, no doubt, when prescription drugs become available over-the-counter advertisements are less likely to tell consumers about the potential harms and side effects.
But how little is too little – and how much is too much?
To say (as many now are) that OTC ads should carry the same warnings as their Rx brethren is to assume that Rx warnings are useful. When it comes to, for example, the so-called “Brief Summary,” that’s an open question (and that’s being charitable). More of what the consumer doesn’t understand isn’t the solution.
Is it the FDA’s responsibility to figure this out? Before we answer that, perhaps a more direct question is, does the FDA have the social science chops to do so? With all due respect to Kit Aikin and crew – this issue will be best resolved through the joint efforts of industry and agency.
And one size may not fit all.
Beyond BTC, it’ll be interesting to see how various Rx-to-OTC applications address the question of consumer education.
Ladies and Gentlemen of industry – it’s time to step up to the plate.
From The New York Post
An ugly way to get insurance
By ROBERT GOLDBERG
Last Updated: 11:23 PM, September 19, 2012
Posted: 11:10 PM, September 19, 2012
The good news: More Americans have health insurance. The bad news: It’s because they don’t have jobs.
ObamaCare supporters hail the drop in the number of uninsured, announced by the Census Bureau last week, as a sign of the new law’s success. In fact, it’s a sign of continued job-market decline and of how many of us have to depend on government programs for far too long.
Nearly 1.4 million more people had health insurance in 2011 than in 2010 — but that includes nearly 800,000 who gained coverage despite not working at all.
In short, the rise comes mainly from more Americans being forced into safety-net programs by declining incomes and reduced job opportunities.
Look at this trend another way: In 2011, the number of people covered by Medicaid jumped 2.3 million, while Medicare saw 2 million new enrollees.
And only 575,000 of those new Medicare cases were people turning 65. Most of the other 1.5 million is associated with the exponential growth in people becoming Medicare-eligible because they’ve filed for Social Security disability coverage.
By comparison, the number of people gaining health insurance via work rose only 730,000.
ObamaCare fans also claim that much of the increase in coverage came from the Obama law’s mandate that young adults can stay on their parents’ health plans until they turn 25.
Indeed, the administration boasted earlier this year that 3 million young adults got insurance that way. But the Census Bureau report shows that health coverage for people in that age bracket rose by only 540,000.
And it’s clear that ObamaCare was not responsible for much of even that increase. Past Census reports show the share of 19- to 25- year-olds on Medicaid or Medicare doubling from 2000 to 2011. That long-term trend — not the ObamaCare mandate — plainly accounts for a good chunk of the rise in coverage of these younger folks.
Slice it another way. The total increase in health coverage for ages 18-24 in 2011 was 825,000. Nearly 331,000 of that was from employer-based coverage. More than 220,000 was from Medicaid enrollment.
So, at most, that’s 247,000 from ObamaCare’s under-25 mandate.
And that gain comes at a hard-to-measure cost: The price of forcing insurers to cover under-25s on their parents’ policies is higher premiums for other people.
Let’s be clear: Medicaid, the Children’s Health Insurance Program and Medicare make health insurance affordable for tens of million of Americans. But that safety net, in place before ObamaCare was enacted, is supposed to be a temporary source of support when we need it, not a permanent solution.
And a jump in the number of Americans who have to use that safety net is nothing to brag about.
Robert Goldberg is vice president of the Center for Medicine in the Public Interest.
http://www.nypost.com/p/news/opinion/opedcolumnists/an_ugly_way_to_get_insurance_etNZJPm74YKgP0euAZJWSM#ixzz271N2B2m9
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.
