Latest Drugwonks' Blog
BioCentury reports that NICE is seeking input on proposed changes to its health technology assessment methodology that the agency said would more explicitly take into account the burden of a person's illness and the wider impact of a disease on people's ability to be part of society. NICE is proposing to measure burden of illness as the proportional shortfall in quality-adjusted life years (QALYs) for those with a disease compared with the expected QALYs for those of the same age and gender without the disease. NICE said evaluating burden of illness as a proportional difference "recognizes the position of those patients who stand to lose the greatest proportion of their remaining health expectancy." The agency noted that the measure "is not particularly sensitive to the age at which people are diagnosed."
What NICE calls "societal impact" would be measured as the absolute difference between the expected QALY in a patient with a disease and the expected QALY in people of the same age and gender without the disease. The agency noted that for an absolute shortfall, "the larger the shortfall, the larger the effect" on society. Comments on the proposed methodology changes are due June 20, with NICE planning to introduce the changes this fall.
In 2010, the U.K. government proposed to establish a system under which NICE would have assessed the value of a new drug and assigned a value-based price. But the 2014 Pharmaceutical Price Regulation Scheme (PPRS) agreement essentially marked the end of value-based pricing as it was originally proposed, with NICE instead shifting toward a "value-based" assessment process.
It’s important to consider VBID in the broader conversation of clinical effectiveness and more specifically HTA modeling a la QALY – because that brings you into the direct path of VSLY – the value of a statistical life year. According to Dr. Frank Lichtenberg of Columbia University, for a healthcare technology assessment scheme (such as the NICE model) to yield valid decisions in practice, it is necessary to have reliable estimates of:
ΔCOST
ΔQALY
and VSLY (Value of a Statistical Life Year)
and his main point is that the devil is in the details.
Lichtenberg believes that incorrect estimates of some or all of these key inputs are often used:
ΔCOST is frequently overestimated
ΔQALY and VSLY are frequently underestimated
And due to these estimation biases, health technologies that are truly cost-effective may often be rejected as cost-ineffective.
Per the recent debate over the utility of new cancer treatments, he makes a very interesting point -- that even though, over the past 30 years, the U.S. Mortality Age-Adjusted Rates for cancer have remained relatively constant -- (leading to such mainstream media headlines as Fortune Magazine's "Why have we made so little progress in the War on Cancer?” and NEJM articles like "The effect of new treatments for cancer on mortality has been largely disappointing” -- the often ignored reality is that 5-year relative survival rates, for all cancer sites, have increased from 50.1% in 1975 to 65.9% in 2000.
Lichtenberg cites two crucial studies, pointing out how health care economists must seriously reconsider the outdated estimates of a QALY:
Viscusi and Aldy: The value of a statistical life for prime-aged workers has a median value of about $7 million in the United States
Viscusi, W. Kip and Joseph E. Aldy, “The Value of a Statistical Life: A Critical Review of Market Estimates Throughout the World,” The Journal of Risk and Uncertainty, 27:1; 5–76, 2003.
and
Murphy and Topel: The value of a life year is $373,000.
Murphy, Kevin M., and Robert H. Topel, “The value of health and longevity,” Journal of Political Economy, 2006.
If the devil is in the details (and it is) -- it's time for a deep dive beyond simplistic and self-serving "comparative effectiveness."
Pharma and the First Amendment: A Proposal From the FDA
By Ed SilvermanOn one hand, the agency is being praised for trying to move the ball forward, given ongoing uncertainty over disseminating material that contains off-label uses. Although physicians may prescribe a drug as they see fit, many drug makers have been fined for promoting their medicines for uses not approved by the FDA.
Yet at the same time, the FDA is being criticized for being overly restrictive concerning some materials and for also failing to specifically address First Amendment issues that have figured prominently in some recent court rulings about drug marketing.
“The fact that they’re starting to pay attention and open up off-label communications indicates they know they have to do a better job of defending the limits they have, and specifying what can and can’t be used and how that’s done,” says John Kamp, executive director for the Coalition for Healthcare Communication, a trade group for medical publishers and advertising agencies. “There are steps forward here. But in some cases, baby steps.”
One portion that was welcomed by industry representatives pertains to clinical practice guidelines, the official recommendations for patient treatment that are issued by professional medical societies. Until now, the FDA had not addressed these guidelines, which are closely tracked by doctors and may include off-label uses. The guidance says that CPGs must be distributed separately from promotional information and should display a statement that some of the products described might not approved or cleared by the FDA, among other things.
By devoting a portion specifically to clinical practice guidelines, the agency has now carved out a separate road map for distributing these missives to physicians.
“They’ve brought some clarity to this issue, which is very important,” says Alan Bennett, an attorney who represents more than a dozen drug makers that last fall filed a citizen’s petition (PDF) with the FDA in hopes of gaining clarity on distributing materials that contain references to off-label uses. The drug makers include Eli Lilly, Novartis, Sanofi, Genentech, Purdue Pharma, Pfizer and Johnson & Johnson.
But the FDA raised some hackles with its other dictums. For one, the agency did not add much understanding to an earlier guidance from 2009 that was devoted to medical and scientific journal reprints containing off-label information. This time around, though, the FDA noted that it does want companies to limit reprints to “adequate and well-controlled clinical” studies.
The earlier guidance also mentioned pharmacokinetic, pharmacodynamics and meta-analysis studies.
This would appear to preclude almost anything other than a double-blind, placebo-controlled study, according to Richard Samp, chief counsel at the Washington Legal Foundation, a nonprofit that frequently agitates for commercial free speech rights. “Against the great weight of medical opinion, FDA continues to insist that other types of studies have no scientific validity,” he says.
There was also disappointment that the FDA did not address the simmering debate over distribution of off-label materials that may be protected by the First Amendment. One closely watched case involved the 2008 conviction of a former pharmaceutical sales rep, who was prosecuted for encouraging doctors to prescribe a drug on an off-label basis.
A federal appeals court, however, overturned the conviction in late 2012 after agreeing that his First Amendment rights were violated because the federal government failed to prove his remarks were false or misleading. But the FDA did not discuss free-speech issues in its guidance at all. “They were silent on this and at some point they’re going to have to address it,” says a disappointed Bennett.
For now, the guidance may be sufficiently restrictive to discourage drug makers from taking many chances. “The hurdles for any meaningful dissemination of peer-reviewed information on off-label uses are very high,” says Arnie Friede, a former FDA associate chief counsel and former senior corporate counsel at Pfizer, who is now at Sandler, Tavis & Rosenberg, a law firm based in Miami.
And he notes that many drug makers may already be gun shy due to Corporate Integrity Agreements. These stem from settlements relating to off-label promotion, and many already regulate the dissemination of this material. “In theory,” he says, “a company subject to a CIA will have to run a dual gauntlet – compliance with the CIA and compliance with the draft guidance. So it becomes a fair question to ask: why bother?”
The Wall Street Journal reports that, “Drug companies and researchers will no longer be able to withhold the results of unfavorable clinical trials, if changes to European law are passed as expected next month.”
The new law would require the results of all trials plus a full clinical-study report to be published within a year of the trial ending. The European Parliament is expected to vote on the new legislation April 3, and it would come into force in 2016.
What the Journal did not report was that in May 2013 the General Court of the European Union prohibited the European Medicines Agency from releasing data from two AbbVie and Intermune trials in an interim ruling, part of a challenge by the two drugmakers to the agency’s decision to grant access to information the companies provided as part of their market approval applications. The challenge is the first to be made to the EMA’s three-year old access-to-documents policy.
The Journal, “Around half of all trial results go unpublished, according to current estimates, including a 2009 paper that looked at 677 studies conducted in different countries. A 2012 paper found just 45% of 635 U.S. National Institutes of Health-sponsored trials were published within 30 months of completion.”
Unreported is that 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.
At the July 2013 Clinical Trials Disclosure and Transparency Summit, Sir Alasdair Breckenridge, former Chairman of the MHRA and currently the Chair of United Kingdom’s Department of Health Emerging Science and Bioethics Advisory Committee, noted that transparency is “a process without a beginning or an end. It is a continuum.” And, “Transparency is like feeding a hungry dog – you more you give it, the more it wants.”
Sir A. suggested four key questions:
(1) Should the public have access to data on which regulatory decisions are taken?
(2) What are the advantages and disadvantages of increased transparency?
(3) What are the key distinctions between transparency and communication (specifically the issue of public health literacy and numeracy – and the “road testing” of released information)?
(4) Will increased transparency lead to increased trust in regulators and industry?
On that last point, Dr. Breckenridge points out that increased transparency does not lead to increased trust. Trust depends on perceptions of honesty and competence, and transparency may expose inherent inefficiencies in a system. And that’s a good thing – if we really mean to make the most of transparency.
Transparency cannot be “for thee but not for me.”
And he offers five keystones for moving forward:
(1) Agreement on timing of release of information
(2) Agreement on nature of information to be released
(3) Standards of protection of personalized data
(4) Standards for meta-analyses
(5) Rules of engagement for observational studies
Per the European Parliament vote, some policy issues to consider:
* Should transparency be a government dictate or a working collaboration between interested parties both private and public – and what role should patients play.
* Should there be formalized transparency consortia? Should it be global?
* What are the implications for intellectual property and the connected question of incentivizing (or dis-incentivizing) investment in innovation? Is transparency a Trojan horse to attack patents and intellectual property rights?
* Can transparency become a competitive advantage as well as a public health imperative?
After all, good things happen when everybody wins.
According to Reuters, “Some U.S. doctors are becoming concerned about the quality of generic drugs supplied by Indian manufacturers following a flurry of recalls and import bans by the Food and Drug Administration.”
"I'm just beginning to realize the gravity of the problem," said Dr. Steven Nissen, head of cardiology at the Cleveland Clinic. "It's terrible and it is starting to get a lot of traction among physicians."
(Maybe he can do a meta-analysis.)
India's drugmakers, a $14 billion industry, reject any criticism that their products are inferior to drugs made in other countries.
"We have heard doctors making generalized statements, without being specific on any product or company," said D.G. Shah, Secretary General of the Indian Pharmaceutical Alliance, a trade group representing large Indian drugmakers. "This is a deliberate and serious campaign to malign the Indian generic industry."
Denial, it seems, is more than just a river in Egypt.
"We are losing control over what people are swallowing," said Dr. Harry Lever, a cardiologist at the Cleveland Clinic who is trying raise awareness of the matter among U.S. lawmakers. "Now, when a patient comes in who is not doing well, the first thing I do is look at their drugs and find out who makes it."
FDA is addressing these concerns by establishing an Office of Pharmaceutical Quality to improve the agency’s scrutiny of brand-name, generic and over-the-counter drugs. The agency is talking with the industry to develop data that may signal which manufacturing plants are straying from standards and need inspection, she said.
FDA now collects such information only during inspections. The thrust of the effort would be to head off potential concerns before the agency wields penalties such as banning products from troubled factories. According to CDER Director, Dr. Janet Woodcock, “We want to use leading indicators. These people aren’t in trouble yet but they could be.”
And, per Commissioner Peggy Hamburg, “All companies must understand that quality is the basis for the public’s trust and confidence in their products and maintaining high quality standards is part of the cost of doing business.” Hamburg said the new office will “improve our oversight of quality throughout the lifecycle of a pharmaceutical product.”
Some Indian physicians do not share these concerns.
"Our drugs are being sold in many countries and being accepted, so we have no issues," said Narendra Saini, Secretary General of the Indian Medical Association, a voluntary body of 215,000 doctors. "How do I know that Western drugs are better than our drugs?"
Not so. The truth is that nation’s across the globe are uncovering serious issues with products manufactured in India. This is particularly true for generic oncology medicines -- where there isn’t room for error.
It’s too simplistic to call these “quality” problems. There’s a range from sub-standard API and manufacturing issues, to excipient changes and, most importantly, bioequivalence and bioavailability standards.
Dr. Joel Zonszein, director of the Clinical Diabetes Center at Montefiore Medical Center in New York, said he is concerned about the quality of generic drugs in general, not just those from India. He cited, as an example, his experience with the diabetes drug metformin.
"When patients open the bottle of medication it smells like dead fish," he said. Zonszein did not know which company made the foul-smelling drug.
Dr. Richard Kovacs, who heads a number of American College of Cardiology committees and sits on its board of trustees, said doctors may need to play a greater role monitoring the medications prescribed by their practices.
"The average U.S. cardiologist has been able to assume that the drugs were safe and effective. It now appears we need to be more vigilant as a profession, and assist the FDA by reporting cases where we are concerned about irregularities in the drugs supplied to our patients," he said.
FDA’s recent draft guidances on bioequivalence for both generic and innovator products, as well as the move towards independent labeling for generic products are additional steps the agency has recently taken to address the issue of drug quality beyond safety and efficacy. And the implications for biosimilars is obvious
(Something else to consider is for the FDA to report BE and BA and PK data in generic labels.)
Small is the new Big means we must think differently about pharmacovigilance. While we must continue to capture adverse event data, we must also strive to capture Substandard Pharmaceutical Events (SPEs). SPEs occur when a product does not perform as expected—perhaps because of API or excipient issues. SPEs can arise because of an issue related to therapeutic interchangeability. When it comes to 21st-century pharmacovigilance, we have to both broaden and narrow our views about bioequivalence to the patient level.
Google “opioid abuse deterrence” and you’ll find a lot of hits from lawyers and elected officials. What you won’t find is a lot of expert thinking from the FDA.
That needs to change.
FDA Commissioner Hamburg’s recent comments (and, in particular, her testimony in front of the Senate HELP Committee) hopefully represent a more aggressive stance by the agency. That’s good. But there needs to be more. The FDA must be the leading voice on the issue of abuse deterrence and the safe use of opioids.
At present, politicians and pundits (not to mention trial lawyers) own the conversation. They're the ones talking about it. They're the ones the media goes to when they write about it. Have a look at a sampling of the press coverage surrounding Zohydro and see who's quoted and what they're saying.
The struggle over control of the opioid abuse deterrence story is, shall say, not going the right way for the agency.
Peggy got it right when she testified that (per Zohydro), “We recognize that this is a powerful drug, but we also believe that if appropriately used, it serves an important and unique niche with respect to pain medication and it meets the standards for safety and efficacy.”
In short – not all opioids are the same and not all patients respond to all opioids in the same way. Further, it’s important to remember that “safe” doesn’t mean 100% safe. Never has. Never will. Not for any medicine. It’s always about the benefit/risk balance.
This is not a new topic. Americans woke up the morning after the Vioxx recall and were amazed to discover that drugs have risks. Good lord. Who let that happen! Avandia, in that respect, was Son of Vioxx. And, like any sequel, new actors were brought in to spice up the story. Now it’s about opioids.
Relative safety is an important conversation. It’s an opportunity for the FDA to help educate the public about the safe use of drugs.
(The foundational proposition of the FDA’s “Safe Use” initiative is that the way to make a drug “safer” is to better educate prescriber, dispenser, and user about the product.) And nowhere is “safe use” a more important issue than opioids.
Dr. Hamburg’s testimony continued, “It doesn’t do any good to label something as abuse deterrent if it isn’t actually abuse deterrent, and right now, unfortunately, the technology is poor.”
As with safety, “abuse deterrent” doesn’t mean that an opioid can’t be abused. “AD” doesn’t mean “100% abuse deterrent” just as “safe” doesn’t mean 100% safe.
Who does that and how it is done is where the rubber meets the road. After all, as the saying goes, everything you read in the paper is true except for those things you know about personally. Such is the case for the drug safety imbroglio currently surrounding opioids.
The FDA must take the lead. And that means more than finessing the label. It means working with CME providers to develop better curricula. It means more targeted REMS. It means enhanced and validated reporting tools for post-marketing surveillance. It means better tools for using that data for better social science in developing tools that can assist prescribers in determining which patients are likely to abuse. “Abuse deterrence” isn’t just a formulation question – it’s a systems question.
Unfortunately complex systems make for bad media coverage, while simplistic, dramatic demagoguing makes for sexier headlines. And when Bloomberg reporter Drew Armstrong notes that “FDA pain drug czar Bob Rappaport has already said the agency would consider jerking Zohydro from the market if an abuse-resistant version become available,” it reinforces the erroneous concept of “100% abuse deterrence.” Dr. Rappaport certainly knows better. The general public does not.
There’s an apt Japanese proverb that bears repeating, “Don’t fix the blame. Fix the problem.” Unfortunately, the recent bashing of opioids (and the FDA’s regulatory decision-making and oversight thereof) isn’t helping. It's time for the grown-ups to step forward and take charge of the debate on drug safety.
What ever happened to “politics has no role at the FDA?”
Yesterday, Senator Joe Manchin (D, WVA) introduced a bill to overturn the FDA’s approval of the opioid Zohydro ER.
That certainly sounds like legislating science.
As a part of his rationale, Senator Manchin noted that the agency approved the drug last year over the objections of an advisory experts that had voted 11-2 to recommend rejection of the drug.
Yes, Senator, that’s why it’s called an advisory committee. Would he make such votes binding on the agency? That’s a pretty radical shift in regulatory policy.
To her credit, FDA Commissioner Peggy, in testimony before the Senate Health, Education, Labor and Pensions Committee on Thursday, defended the agency’s October approval of Zohydro ER.
"We recognize that this is a powerful drug, but we also believe that if appropriately used, it serves an important and unique niche with respect to pain medication," Dr. Hamburg testified.
Senator Joe isn’t alone in his well-meaning but misguided attempts to legislate science. Senator Charles Schumer (D, NY) is urging Health and Human Services Secretary Kathleen Sebelius “to overturn the government’s approval of a new powerful prescription opioid, Zohydro ER” (hydrocodone), “until it has been made abuse-proof.” According to reports, Schumer “believed there was a ‘decent chance’ that” Sebelius would revoke the FDA approval.
In “Personalized Medicine and Responsible Access to Pain Medication” (a white paper based on the Center for Medicine in the Public Interest’s September 2013 Capital Hill conference), Dr. Douglas Throckmorton, CDER’s Deputy Director, for Regulatory Programs and the FDA’s point person on opioids, writes,
We understand that for the millions of Americans experiencing an acute medical need or living with chronic pain, opioids, when prescribed appropriately, can allow patients to manage their pain as well as significantly improve their quality of life. However, we have also become increasingly concerned about the abuse and misuse of opioids. We are challenged with determining how to best balance the need to ensure continued access to patients who need these medications while addressing concerns about abuse and misuse.
FDA must walk a difficult public health tightrope, balancing patient need, medication safety, and (in the case of opioids), the dangers of abuse.
In addition to Senator Manchin’s call for legislation and Senator Schumer’s call for Secretarial interference, this careful balance is also being called into question by 28 state attorneys general who, in a letter to FDA Commissioner Margaret Hamburg, ask the agency to “reconsider its controversial approval of the powerful new narcotic painkiller known as Zohydro.” The attorneys general are concerned that the medicine lacks “an abuse-limiting formula.”
Was the approval “controversial?” Well, it depends what you mean by “controversial.” It’s controversial because the issue of opioid abuse is controversial. And that’s an important difference. Nobody said the FDA’s job was easy.
Noble Prize winner Joshua Lederberg once observed that the failure of regulatory legal and political institutions to integrate scientific advances into risk selection and assessment was the most important barrier to innovation in public health. Lederberg noted that in the absence of such changes, “The precedents affecting the long-term rationale of social policy will be set not on the basis of well-debated principles, but on the accidents of the first advertised examples.” And there isn’t a better perspective-setting proposition when it comes to the issue of Zohydro than that quotation.
Policies and regulations that seek to limit risk are often shaped by the immediate fear of sensational events. This perspective is commonly referred to as the Precautionary Principle, which, in various forms asserts that unless innovators can demonstrate that a new technology is risk free, it should not be allowed into the marketplace. Moreover, any product that could possibly be dangerous at any level should be strictly and severely regulated. But precaution is not always safer than the alternatives.
Pierre Trudeau once said, “There’s no place for the state in the bedrooms of the nation.” But what’s the appropriate place for the state in our nation’s pharmacies and medicine chests? Should regulation be shaped by factors other than science?
According to the CDC in 2008, there were 14,800 opioid overdose deaths. Half of those, the CDC has claimed, involved opioids and other illicit substances, whether it’s cocaine or heroin, or alcohol. They also mentioned that alcohol was involved in many of those deaths but they don’t actually tell us the numbers. So conservatively, half or 7,400 deaths occurred in 2008 from opioid overdose. The same year from CDC’s own statistics, there were 36,500 suicides. There also were 24,000 alcohol-induced deaths and that doesn’t count other related alcohol deaths like drunk driving. The bottom line is that the opioid numbers do not even come up in the CDC’s list of the top 15 causes of death of Americans
It’s important to add to this “epidemic” perspective, the fact that people suffering from chronic pain are under-served by existing therapies. A recent IOM report that was issued in June of 2011 found that 100 million Americans are now living with chronic pain. That’s a third of the U.S. population. Ten million of those have pain so severe that they are disabled by the pain. The report also said that pain costs the U.S. economy about 600 billion dollars a year in lost productivity and healthcare cost.
The vast majority of people who use opioids do so legally and safely. A subset, approximately four percent, use these medications illegally. In fact, from 2010 to 2011, the number of Americans misusing and abusing opioid medications declined from 4.6% to 4.2%.
And the FDA’s decision was “controversial?” Really?
Rather than dealing with the problem of abuse with sledgehammer solutions, Senators’ Manchi and Schumer, and the various state AGs should focus on potential solutions such as:
* The structure and impact of programs such as the recently instituted by CVS initiative (detailed in a recent New England Journal of Medicine perspective piece) where, through the use of “Big Data”, the chain pharmacy identified outlier prescribers and took appropriate and responsible action.
* The role of the 21st century pharmacist in improving drug safety and medication adherence via more proactive and remunerated patient education? How can pharmacists become better integrated beyond Med Guides into the FDA’s Safe Use of Medicines initiative? When will pharmacy synchronization really kick into gear, and how will states help to jump-start these important initiatives?
* Government and legislative initiatives such as the Stop Act (H.R. 486), which focuses on tamper-deterrent formulations and the continued development of those. Also, Senate Bill 1277 (sponsored by Senator Barbara Boxer, D/CA) which would establish a commission to bring all of the stakeholders together to have discussions about how to approach this issue so that law enforcement, providers, patients, and pharma can debate the issues and reach common ground.
* The appropriate role of tamper-resistant technologies. They are part of the solution, but they’re not the whole solution. We need to develop policy options that focus on the prescriber/patient relationship, and a professional assessment of what’s the risk involving this patient. Is the patient is going to tamper with the medication and potentially expose themselves or others to some danger. We have to do a better job (via CME and other methods) of training physicians and other prescribers on how to do these kinds of assessments.
And, most importantly, we need to keep the needs of patients front and center.
Whatever your position on the issue of opiods, the proper venue for this decision is not the office of the Secretary of HHS or the halls of Congress or the courts -- but rather the office of the FDA Commissioner.
OPDP reminds us that it's not the platform -- it's the content. (Or in this case, the lack thereof.)
According to an article in Medical Marketing & Media,
The latest proof that the FDA is not giving social media outreach wiggle room, even though communications guidelines are not due out until this summer, is an untitled letter to Institute Biochimique and US partner Akrimax Pharmaceuticals over a Facebook page for its hypothyroidism drug Tirosint.
Not so fast MM&M.
It seems that, per OPDP, the FaceBook page failed to “communicate risk information” and omitted material facts.
There should never be “wiggle room” for that. Not ever – especially for a drug with a boxed warning.
“Wiggle Room?” Hardly.
How about “proper oversight?”
Well done, OPDP.
On January 6th, CMS issued a proposed rule that would result in foundational changes to Medicare Part D and negatively impact America’s seniors, and other constituencies. Most disturbingly (if not surprisingly) it reveals the Administration’s authentic view of Part D by attempting an unprecedented level of government interference with what was intended to be a competitive, market-based proposition.
On Monday, CMS Administrator Marilyn B. Tavenner said the agency would not pursue the proposal. “Given the complexities of these issues and stakeholder input, we do not plan to finalize these proposals at this time.”
Translation -- The draft rule is dead.
Senator Mitch McConnell said he was “pleasantly surprised to see the Obama administration backtracking on a number of proposals that would undermine the highly successful Medicare drug program.”
Senator Ron Wyden also welcomed the administration’s decision to drop some of the Medicare proposals. In a letter to Ms. Tavenner last month, Mr. Wyden and 19 other committee members said the proposals would “disrupt care for millions of beneficiaries and unnecessarily interfere with a successful program.”
For a more detailed look at the now moribund CMS proposals, see Bizarro Part D.
Congratulations are due to Administrator Tavernner for acknowledging that the proposed CMS rule was a mistake – and to shelve it.
BioCentury reports that “President Obama has again proposed to shorten the exclusivity period for innovator biologics in his FY15 budget proposal. According to HHS's summary, the president's budget request includes a proposal to cut the exclusivity period to seven years from the current 12 years. Obama proposed the same change in his FY14 budget request.”
It’s hugely disappointing that the same man who (as a United States Senator) once said that …
“Realizing the promise of personalized medicine will require continued federal leadership and agency collaboration; expansion and acceleration of genomics research; a capable genomics workforce; incentives to encourage development of genomic tests and therapies; and greater attention to the quality of genetic tests, direct-to-consumer advertising and use of personal genomic information."
… is now advocating a policy that would result in precisely the opposite.
After speaking (and in a widely quoted op-ed in the Wall Street Journal) about the need for America to embrace innovation – President Obama is trying to make it more difficult, specifically when it comes to the desire to invest in pharmaceutical innovation – a sure bet under no circumstances.
Patent exclusivity funds an innovator company’s research and development efforts. If the President’s proposal becomes law, the US would provide less data protection for innovative biologics than Europe.
12 years of exclusivity also gives hope to those suffering from rare diseases or conditions. If innovator companies think they will have a short time before a follow-on versions of their products hit on the market, they will likely only focus on drugs for major diseases and conditions -- potentially ignoring ailments that are less common, but equally as serious, to those suffering.
If innovation is one of the key answers to our national economic recovery, then the President should abide by what he said, “Our economy is not a zero-sum game. Regulations do have costs; often, as a country, we have to make tough decisions about whether those costs are necessary. But what is clear is that we can strike the right balance. We can make our economy stronger and more competitive, while meeting our fundamental responsibilities to one another.”
OTC Statins: More Questions than Answers
Much news lately about Pfizer’s desire to move Lipitor into the OTC category.
OTC statins. Not a new conversation, but certainly a timely one as we continue to face not just Hyperlipidemia – but medication adherence (and particularly for chronic, asymptomatic conditions).
Are statins “safe enough” to be available without a prescription? Well, with the appropriate caveat that no drug is 100% safe, it’s pretty fair to say that their safety profile is excellent – for Rx products. But is the same true if they were available OTC?
Here’s some history.
In 2005, an FDA advisory panel voted down a bid by Merck & Co. and Johnson & Johnson to sell lovastatin (Mevacor), without a prescription. Several panel members said the FDA should consider establishing a behind-the-counter system that would allow consumers to purchase lovastatin from pharmacists much like the British are allowed to purchase simvastatin (Zocor), another cholesterol-lowering drug. Most panel members said that, if such a system existed in the U.S., they would have voted to allow Mevacor to be sold without a prescription.
(Other countries with behind-the-counter status include Australia, Canada, New Zealand, Denmark, Germany, Italy, the Netherlands, Sweden and Switzerland.)
Then, in 2007, another proposal to offer lovastatin over-the-counter was rejected by an FDA panel, primarily due to the fear consumers might not select the drug appropriately.
“It is not clear that the benefits to patients of lovastatin being over-the-counter outweigh the risks, although the risks are small,” Arthur Flatau, PhD, said during a joint meeting of the Nonprescription Drugs Advisory Committee and the Endocrinologic and Metabolic Drugs Advisory Committee. “Clearly, there are a lot people who are not on statins and should be on statins; putting the drug over the counter will not increase the number of patients who take it.”
The vote was 10-2 against over the counter approval of lovastatin with one abstention. The majority of panel members who voted against lovastatin over the counter felt consumers were unable to make a decision regarding whether they should be taking a statin.
Can a patient self-diagnose and self-dose? Do symptoms hide another, potentially more serious, underlying condition? And what of safety concerns?
Per a New England Journal of Medicine written by the chair of the FDA advisory committee, "Some docs argue that increasing access to statins could prevent heart attacks and strokes, which in turn would lower health care costs. Overall, a study of an OTC Mevacor (Merck's statin) showed 30 percent of patients who thought they should take the drug actually had less than a 5 percent risk of a heart attack or other cardiovascular event in the next 10 years, and were therefore unlikely to benefit."
Does this open the door for a so-called “behind the counter” (BTC) category? CDER Director Janet Woodcock has spoken out in favor of such strategies since they would allow switch candidates with greater self-selection obstacles to be available without a prescription.
This is an important debate as well as a "teaching moment" for American pharmacists to communicate the crucial role they play in 21st century American health care.
Pfizer recently started a 1,200-patient clinical trial to test if consumers taking OTC Lipitor and getting their own blood tests improve their cholesterol levels and then make the right decisions based on the results of a second blood test. (These blood tests, in the real world, would be administered at the pharmacy.)
What additional questions should be asked when it comes to the OTC statin debate? Here are a few:
* Should any chronic medications be available OTC? (This is a very big “beyond statins” question that hasn’t been widely discussed … yet.) Most Rx-to-OTC switches have been for the treatment of acute, transient symptoms of allergies, heartburn, etc.
* Isn’t this a de facto BTC play? After all, the pharmacist will have to advise, test, and dispense. Isn’t that beyond the scope of FDA’s existing regulatory authority?
* Is an OTC “Drug Facts” label up to the task of properly communicating the most important benefit/risk information about statins (or, for that matter, about any OTC product)?
* Even at a 10mg dose?
* Per that second blood test, what does “success” look like?
* What if the patient doesn’t come back for a second blood test?
* What about the financial burden on the consumer? Rx products are reimbursed. OTC products are not.
* And, to that point, when there is an increased financial burden on the patient (i.e., raised co-pays) – adherence declines. Would OTC statins further exacerbate the problems with statin adherence?
* If, after the second pharmacist-implemented blood test, the patient is told to see their physician – why shouldn’t they just have gone to see their physician in the first place?
* If Pfizer is granted the OTC designation for Lipitor and then other statins follow suit (a pretty safe supposition), how are patients supposed to choose which statin is “best for them” minus a physician's “clinical experience?”
* What about prospective patient (aka “consumer”) education? Pfizer says it hopes to persuade regulators to approve OTC Lipitor by using "new and creative ways" to communicate instructions for use.
All this to say that it’ll make for an interesting and important conversation.
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