Latest Drugwonks' Blog
Sins of omission are seldom fun, and (per Health Care’s Trick Coin, NYT, 2/3/13), Ben Goldacre makes a number of serious mistakes – specifically the claim that the Clinicaltrials.gov registration requirement in FDAAA isn't implemented and that only full transparency/publication of clinical trial will address the issue. As the former senior government official in charge of clinicaltrials.gov, it’s important to look at the facts – and the numbers.
In 2000, the National Institutes of Health (NIH) launched ClinicalTrials.gov to provide public access to information on clinical studies. Although it initially contained information primarily on NIH-funded research, it has been expanded to include both publicly and privately supported clinical research.
Since the launch of the site, it has been enhanced to significantly increase data sharing. The ClinicalTrials.gov database includes information on nearly 140,000 clinical trials in all 50 states and 182 countries.
Is anyone accessing this wealth of information? Yes! The NIH reported last year that ClinicalTrials.gov “receives more than 95 million page views per month and 60,000 unique visitors daily.
Facts do not cease to exist because they are ignored. Mr. Goldacre should realize that reality, although sometimes inconvenient to ones argument, remains reality.
Great BioCentury lead article by Steve Usdin, Debating Limited Use.
Usdin writes:
FDA is asking the public to consider whether it should supplement the current all-or-nothing approval structure with a system that would couple approval of selected new drugs with measures designed to discourage off-label use.
The agency says it could approve drugs for conditions such as antibiotic-resistant infections and life-threatening obesity based on small, fast trials if it were confident use would be limited to well-defined populations.
There is little controversy about approving drugs based on relatively small studies that demonstrate high levels of efficacy in tightly targeted populations. But FDA’s suggestion that it could work with physicians and payers to limit use of a marketed drug in the absence of documented safety concerns is controversial.
To say the least.
Patient and medical groups support the concept of a limited-use pathway, and the President’s Council of Advisors on Science and Technology (PCAST) has endorsed the idea. PCAST’s recommendation to create a Special Medical Use (SMU) pathway was drafted in close consultation with senior FDA officials and reflects the agency’s thinking.
But, whether or not you believe the FDA has the legal authority for a “new” pathway, Janet Woodcock nails the problem dead on:
“We can indicate things for small populations, but often we are very concerned there might be a temptation to use them much more broadly.”
There are many important issues, let’s discuss two.
First – does the FDA have the authority, the resources, and the desire to direct the practice of medicine? Can the agency really do anything other than suggest, via labeling, how physicians should prescribe approved medicines? No doubt they can deter pharmaceutical companies from detailing or even discussing off-label use via prior agreement (and Caronia notwithstanding). Whether or not doctors are “tempted,” however, is another matter entirely. Is the FDA going to “ban” certain scientific publications or conference presentations? Is the FDA going to add a new tenet to the Hippocratic oath, “First do no reading?”
It’s a slippery slope indeed.
Woodcock added that FDA is not seeking to ban off-label prescribing of drugs approved through a new limited use pathway. The agency is interested in exploring whether payers might play a role in reducing inappropriate use, she said.
More power to the payers? Is that something we want?
Next is the issue of whether such expedited approval pathways are in the best interests of the sponsor. While there’s no doubt getting new treatments for serious and life-threatening diseases to market more swiftly is a good thing, is the threat of having a product license revoked after a “test” period in the sponsor’s best interest? Isn’t it a penny-wise, pound-foolish proposition? It depends. What is certain is that such decisions should not be driven by financial considerations of biotech venture capitalists or the panjandrums of Wall Street.
Naïve? Perhaps -- but none-the-less disturbing.
Is FDA PCAST-ing it’s net too wide?
Whenever there is authority, there is a natural inclination to disobedience.
-- Thomas Haliburton
A group of six Congressional Republicans sent a letter to HHS's Health Resources and Services Administration seeking details on the agency's audits of the eligibility of healthcare entities for the 340B drug discount program. The program requires manufacturers to give deep discounts on outpatient drugs to hospitals and clinics that bear the brunt of providing healthcare to low income and other special populations.
HRSA began the audits in FY12 after a 2011 report from the Government Accountability Office said HRSA's oversight of the 340B program was "inadequate to provide reasonable assurance that covered entities and drug manufacturers are in compliance" with the program's requirements. According to the letter, during 2012 HRSA decertified about 250 entities from the 340B program. The agency said it recertified more than 3,800 entities during the same time period.
The lawmakers are seeking information on audits that HRSA is currently conducting. The lawmakers also are seeking information on the decertified entities, including whether the agency plans to take legal action or recoup any ineligible 340B discounts.
The letter was sent by Sens. Chuck Grassley (R-Iowa), Lamar Alexander (R-Tenn.), Orrin Hatch (R-Utah) and Michael Enzi (R-Wyo.), as well as Reps. Joe Pitts (R-Pa.) and Bill Cassidy (R-La.). The lawmakers asked for a written response by Feb. 14. HRSA said it is working on a response.
Clearly, the practice of medicine, perhaps better described as the delivery of healthcare, is undergoing a radical, permanent change, at least for the foreseeable future. After all, we are only a few weeks into the first year of ObamaCare, and already HHC, one of the largest hospital corporations in the country, has decided to hold their physician employees financially responsible for the mandatory changes outlined by CMS. The complexity of these changes makes their adoption into current practice a daunting task for many physicians.
The simple fact is, that the future of medicine looks very different than it did when many of today’s doctors started medical school, even for those who have graduated in recent years. For those who entered the field to treat patients, cure disease and make a real difference in the lives of others, the current tasks that consume much of their time and energy are carrying them further and further away from that goal. The optimists in the field would like to believe that pay-for-performance is simply a resetting of the status quo, which will take considerable time and effort, but ultimately benefit our profession and our patients in the long term.
I am hesitant to agree with this view for two reasons, among others. First, I believe that many physicians are already at or near capacity in terms of their ability to deliver care, both in terms of organizational resources, and personal time and energy. Many individual and small-group practices simply do not have the resources to understand and implement the constantly changing mandates from CMS. Therefore, when you hand them a forever evolving checklist of arbitrary measures that they must follow in order to be reimbursed properly, you only increase confusion and frustration, and do little to impact productivity or foster a system that delivers better care.
Secondly, for any physician who sees their reimbursement cut by providing “sub-optimal care”, as deemed by CMS, what is to stop them from refusing to serve their sickest, most chronically ill and frequently hospitalized patients? In so doing, they raise the “quality” of care they provide, and lower the cost at the same time (they will not be responsible for those sick patients when CMS evaluates them the next year). Such a reaction to pay-for-performance would only further accelerate a current trend in medicine, which is seeing many physicians refuse to accept new Medicare patients.
It is impossible to forecast how pay-for-performance will ultimately impact the quality of care we provide, and the cost at which we do so. But one thing is certain; the job of physicians providing that care becomes more difficult every day.
Read the full piece here.
Small is Big.
Bob Temple said he "would like to see more" comparative effectiveness trials for symptomatic treatments to help identify potential responders. In particular, Temple said trials that randomize non-responders to a drug to receive both that drug and an alternative drug have "a lot of potential" but are almost never done.
"For example, you could take people who don't respond to a migraine drug and randomize them back to a new migraine drug, the old migraine drug the one they didn't respond to, and a placebo. If it's true that there are individual differences that are important, then the new drug ought to be able to show its advantage over the drug that didn't work," he wrote in a post on FDA's From a Clinical Perspective blog.
When asked whether institutional review boards (IRBs) would approve such trials, Temple said there is no ethical issue in an informed patient. He added that such trials would not be done for indications where "not working would be dangerous."
This seems to jive with what Dr. Joe Selby (PCORI’s executive director) told me the other day – that he believes PCORI should focus on funding “narrow” clinical trials aimed at smaller, more targeted populations, that PCORI's mission is to ensure that CER helps to advance the cause of personalized medicine and “the right treatment for the right patient at the right time.” Bravo.
If Joe Selby can be the Good Witch of Comparative Effectiveness Research, so much the better. I think he’d look lovely in ruby slippers.
As would Bob Temple.
"YONKERS, N.Y., Jan. 30, 2013 /PRNewswire-USNewswire/ — In its March issue, Consumer Reports shines a light on oversold cancer screenings that might confuse rather than clarify. The report evaluates eleven cancer screenings, finding that eight should be avoided.
The report, available online at www.ConsumerReports.org and wherever magazines are sold, notes that the Ratings are for people who are not at high risk and without signs or symptoms of cancer
Screening tests for cervical, colon, and breast cancers are the most effective tests available, according to Consumer Reports’ first Ratings of cancer-screening tests. But most people shouldn’t waste their time on screenings for bladder, lung, oral, ovarian, prostate, pancreatic, skin, and testicular cancers. The Ratings are based mainly on evidence-based reviews from the U.S. Preventive Services Task Force, an independent group supported by the Department of Health and Human Services."
Oversold? And given that cancer is now the leading form of death, and that treatments are increasingly targeted to cancer causing mutations that can be detected earlier, who is not at risk? Should we wait until Obamacare autocrats determine what tests should be paid for? Will people actually pay Consumer Reports to peddle medical malpractice?
I’m in Riyadh, Saudi Arabia where I just spoke at the first Saudi Quality Forum (sponsored by King Saud University). I also had the opportunity to meet with the leadership of the Saudi Food and Drug Authority (SFDA) -- which is also the national reimbursement agency. (And no product gets licensed without first concluding price negotiations.)
And you thought FDA swings a big stick.
My suggestion to their executives is that they form an Office of Policy and Planning – and that one of the first items on the agenda be chairing a regular meeting of industry (both innovator and generic) and academia to address issues of common interest including API and excipient quality, biosimilars (specifically the issues of biosimilarity and interchangeability), 21st century pharmacovigilance, generic interchangability, and other issues that fill the Arabian regulatory gulf -- like re-registration.
The SFDA aspires to be not only the gold standard for the region, but also a world-class regulatory agency. But to do so they must recognize their responsibility to be both regulator and colleague to industry and an innovation enabler. Sound familiar?
My favorite sound-bite from the conference came courtesy of the SFDA’s Mohammed Dahhas (Executive Director of Inspection and Law Enforcement, Drug Sector): On the issue of quality by design, “Quality is the magic key.”
My favorite new concept came from Accenture’s Pierre Anhoury, who introduced the conference attendees to notion of “value vigilance” – a new way to view post-approval value-based reimbursement via pharmacovigilance, quality of life, therapeutic benefit, and pharmaco-economic impact. Maybe we should call it Phase 4.1.
(Have a look at Anhoury’s new white paper on the topic, Approval is Nothing: Why Pharmaceutical Companies Need a Value Management Operating Model.)
Wouldn’t it be NICE to bury the QALY in the sands of Saudi?
"We are thankful to all of you who have prayed for Michal and expressed your support in other ways. Here is another opportunity for those interested.
On March 3, 2013 both our sons-in-law, Ben Coleman (Michal’s husband) and Sean Wasserman, will be participating in Cycle for Survival, the national, indoor team cycling event that has raised more than $20 million in support of life-changing research on rare cancers at Memorial Sloan-Kettering Cancer Center, one of the world's premiere cancer research institutions.
100% of the funds raised through this ride go directly to MSKCC's research of rare cancer, like Synovial Sarcoma, making us feel very personally connected to this cause. With your help, we can move closer to finding out how to cure cancers like the one Michal is battling right now.
The 2012 ride donations were already put to work in twenty-eight different MSK labs and clinics – targeting a wide range of rare cancers. This progress – and the hope it brings to patients and their families – is only possible because of thoughtful contributions from people like you! We are asking you to join the battle and make a gift to support our ride against cancer. The link below will bring you to our fundraising page, where you can make a tax-deductible online donation."
http://mskcc.convio.net/site/TR/CycleforSurvival/AG_Cycle_Event?pg=team&fr_id=1818&team_id=26100
How many times have you read, “The FDA is not required to follow the advice of its advisory panels but usually does."
Except when it doesn’t.
Recently an agency advisory panel voted against recommending making oxybutynin transdermal patch (Oxytrol) available over-the-counter (OTC) for overactive bladder (OAB) in women.
In their 5-6 vote, panelists on the FDA's Nonprescription Drugs Advisory Committee noted their concerns that women would use Oxytrol thinking they had OAB when they really had some other ailment that needed a physician's treatment. They also were concerned about men using the product off-label.
Some also were worried about the high amount of potential misuse -- whether it was by patients who did not have indications for proper use, or those it was meant for that didn't use the product correctly.
Well, today the FDA ruled that a patch containing oxybutynin (Oxytrol) for controlling overactive bladder may be sold over-the-counter for women 18 and older.
Men will continue to need a prescription for the drug, the agency said. The OTC product will be marketed by Merck as Oxytrol for Women.
In considering an Rx-to-OTC switch, the FDA looks to see whether patients can use the product safely without the oversight of a physician or pharmacist. This includes ensuring that the right patients use the drug in the appropriate way ("safe use"). The agency is not evaluating the risk-benefit of the product, since that was done earlier when it was approved as a prescription drug.
But, considering all of the issues surrounding this particular switch (conditions can cause symptoms similar to those of OAB, including urinary tract infection, bladder malignancy, pregnancy, prostate disease, and uncontrolled diabetes mellitus), AdComm panelists (who voted no) said those conditions need a physician's care, and an OTC oxybutynin could delay treatment. Shouldn’t the FDA have asked Merck for a “safe use” plan – in addition to the age restriction? Sort of REMS for OTC products?
Note to FDA – there’s an app for that.
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.
