Latest Drugwonks' Blog
The Generic Pharmaceutical Association never misses an opportunity to miss an opportunity. They are balking at continuing to negotiate the design of a biosimilar user fee program that is independent of other user fees and has its own baseline appropriations trigger.
The disagreement stems from a proposal by GPhA and a representative of potential biosimilar sponsor Momenta Pharmaceuticals that biosimilar reviews remain part of the Prescription Drug User Fee program through fiscal year 2017, the end of the first biosimilar program cycle, according to minutes of a July 18 meeting.
The tactic could be a way to lower the cost of a biosimilar application. If the agency is forced to include biosimilars in the PDUFA program, it likely would have a more difficult time arguing it needed a strong funding base to ensure the program functions properly.
GPhA said it could not continue “detailed negotiations regarding volumes and metrics without agreement to parity with the PDUFA user fee program.”
The position would seem to reverse one taken during a July 11 negotiation. Minutes indicated “industry stakeholders” and FDA agreed to support a flat product development fee of about 10% of the marketing application fee for the fiscal year while a biosimilar product was in the IND stage.
It is unclear whether FDA could send a commitment letter to Capitol Hill for approval without support from a major trade group involved in the negotiations.
If FDA went ahead with a commitment letter for a separate biosimilar user fee program and GPhA wanted to press the issue, the generic group would presumably need to convince legislators that its interpretation of the 2007 bill creating the new approval pathway was correct.
“Facts are stubborn things” – John Adams
Médecins Sans Frontières (MSF) should be called Médecins Sans Facts.
MSF reports (correctly) that “while countries are rolling out new tests that will enable them to diagnose more patients with drug-resistant tuberculosis (DR-TB), a worldwide shortage of the drugs to treat these patients is likely.”
Not quite.
The news item generating this story comes from South Africa, which has the world's fifth-largest burden of multi-drug resistant (MDR) TB cases. According to Norbert Ndjeka, director of DR-TB, TB and HIV at the South African National Department of Health, the government will replace all microscope-based TB diagnoses with faster, more sensitive GeneXpert testing within two years, making it the world's largest user of the machine.
Good news. But here’s the MSF spin:
But while more patients may get diagnosed, their access to treatment remains precarious as a limited number of approved drug producers keep many DR-TB prices high and supply uncertain, according to Dr Eric Goemaere, MSF's senior regional adviser.
It’s the familiar refrain from our friends at MSF: Blame industry! Blame international intellectual property (IP) protection! Convenient and consistent – and untrue. Médecins Sans Facts.
The truth of the matter is that the fault for shortages lies with all too familiar misguided government policies – in this case the government of South Africa and their myopic focus on lowest price. Combined with a concerning lack of transparency, utter unpredictability and the exploding processing costs of their regulatory system, it all adds up to delays and drug shortages of not just medicines for TB – but for many other critical healthcare products.
Mr. Ndjeka has admitted that South Africa's regulatory Medicines Control Council (MCC) has been laboring for years under a backlog in drug registrations, including those of some fixed-dose antiretrovirals long available in other nations. South Africa now pays a private company to import the drug through a special application to the MCC.
So what does MSF recommend doing beyond their criticism of IP and the innovator pharmaceutical industry? Ignoring Economics 101, they recommend lowest cost "access to essential drugs" -- which just further exacerbates the medicines supply problem.
Médecins Sans Facts continues to call for countries to avert the looming crisis by “improving drug forecasting, negotiating better prices and accelerating national medicines registrations.”
As Mark Twain said, “Get your facts first, then you can distort them as you please.”
It would be helpful if groups like MSF took a longer term view -- encouraging multiple suppliers of medicines through more stable and predictable pricing versus their usual and customary (and wrong) focus on lowest cost. If MSF really wants to be part of the solution, they should consider combining efforts with industry to help streamline the complicated and costly regulatory process in South Africa (and in many other nations of the Developing World). Harmonizing regulatory practices to align with evolving global standards (as called for recently by US FDA Commissioner Dr. Margaret Hamburg) and pressing domestic regulatory officials to respect timelines and transparent performance criteria, would make a huge difference for patients in countries like South Africa.
Why can't MSF advocate new drug approvals in places like South Africa within 90 or 180 days for products already approved leading regulatory agencies in Europe, Japan, and North America? Should South African patients really wait 2-5 years for access to promising new medicines that are already licensed for use in dozens of other countries? Where is the activist outrage about these inexcusable regulatory delays?
Perhaps a better question (at least for starters) is why won’t MSF and their fellow travelers opt for a more collegial and logical agenda?
Perhaps the answer to that question was best addressed by George Orwell who wrote that “All political thinking for years past has been vitiated in the same way. People can foresee the future only when it coincides with their own wishes, and the most grossly obvious facts can be ignored when they are unwelcome.”
When I served at FDA we signed an MOU with PhRMA that required its member companies to notify the agency when instances of counterfeit medicines came to the attention of manufacturers.
It got the job done – minus additional federal regulation.
Today we face a different problem – drug shortages – but a similar decision tree: regulation or public-spirited public health cooperation.
Minus the latter, we will get the former.
Senators Amy Klobuchar (D, MN) and Bob Casey (D, PA) have introduced legislation to require drug manufacturers to give “proper prior notification” to FDA when there is going to be a drug shortage.
Further, Klobuchar (D, MN) and Richard Blumenthal (D, CT) have formed a bipartisan group to work on the issue of drug shortages.
At their request, the FDA will hold a hearing on the matter September 21, and the General Accounting Office will review the problem.
It’s time for FDA and PhRMA to get the job done.
Legislation takes longer and leads to mission creep.
BioCentury reports that the FDA has dentified eight priorities in the Strategic Plan for Regulatory Science: preclinical toxicology; personalized medicine; manufacturing; evaluation of emerging technologies; using information sciences to improve health outcomes; food safety; medical countermeasures; and communication with consumers and professionals.
The agency is seeking to improve the prediction of product safety through new animal models that consider both disease progression and co-morbidities. The plan also calls for FDA to collaborate with academia, industry and global regulatory agencies to develop and refine clinical trial designs. Such a collaboration would identify and evaluate improved endpoints and related biomarkers for areas where "optimal" endpoints are lacking, such as for osteoarthritis, gene therapy, ophthalmic indications, tumor vaccines and stem cell-derived therapies
CDRH has released two draft documents on approval process and guidance on its evolving approval process and planning clinical trials.
The first document explains the Center’s procedures for approving diagnostic and therapeutic devices -- how it weighs benefits and risks, judges the seriousness of a disease or condition, estimates how many people would use a device, and gauges availability of other devices for the same condition.
“Availability of other devices?” Really? Shouldn’t Shuren and Company stick to safety and efficacy? Where’d this third leg come from?
Sounds like insidious mission creep of the comparative effectiveness variety.
The second document explains the agency's expectations for medical device clinical trials, and suggests companies pre-submit protocols for the design of pivotal studies. Both drafts are open to public comment for 90 days, beginning August 15.
The IRS has "released what it's calling “temporary regulations” under which brand-name drugmakers must pay fees "to help fund" health-reform law provisions.
This was, as you will recall, part of “the deal.”
The regulations request payments of $2.5 billion in 2011 and are due by September 30th. Additionally, IRS calls for $2.8 billion in each of '”fee years” of 2012 and 2013; $3 billion for fee years 2014 through 2016; $4 billion for fee year 2017; $4.1 billion for fee year 2018; and $2.8 billion for fee year 2019 and thereafter.
So what’s “temporary?” And what about those who are pounding the podium about rebates for dual eligibles?
Just asking.
According to reporting in Congressional Quarterly, although pharmaceutical companies have to "pay fees," they will garner "far more sales as millions of the uninsured gain coverage."
The requirement applies to companies with annual drug sales of "$5 million or more" to Medicare "Parts B and D"; Medicaid; and Veterans Affairs, and Defense Department and TRICARE programs.
All of a sudden the Mainstream Media (highlighted by a much ballyhooed New York Times Week in Review op-ed by Zeke Emanuel) has discovered the problem of drug shortages.
Except it’s not a new problem.
According to a recent analysis, the frequency and impact of drug shortages have risen to critical levels, more than tripling since 2005, and affecting all segments of the healthcare community. In 2010, over 240 drugs were either in short supply or completely unavailable and more than 400 generic equivalents were backordered for greater than five days. In most instances, these did not progress to critical shortages, but point to instabilities in the supply chain that cause national concern. Many of the drugs identified in 2010 remain unavailable or in short supply in 2011.
Seventy-seven percent of drugs in short supply in 2010 were sterile injectable products, critical in the acute care setting. Recent media coverage highlights the plight of patients and physicians faced with shortages for cancer drugs, anesthetic agents, and critical care medications that have contributed to delays in treatment and surgery, or changes in care plans. Drug backorders cause patients to receive substitute therapies that add expense to patient care.
A major reason for shortages is quality/manufacturing issues. However there are other reasons such as production delays at the manufacturer and delays companies have experienced receiving raw materials and components from suppliers. Discontinuations are another factor contributing to shortages. (The FDA can't require a firm to keep making a drug it wants to discontinue.)
It is time not to fix the blame – but to fix the problem.
Let’s start with the FDA.
In 2010, there were 178 drug shortages reported to the FDA. Is that a solid number? Hard to say, because current regulations do not require companies to notify FDA of shortages. The only requirement is that companies inform FDA six months in advance for discontinuations of sole source, medically necessary drugs.
(In 2010, for example there were 38 shortages prevented due to companies notifying FDA voluntarily of potential issues that could lead to shortages and FDA was able to work with the company to avoid a shortage.)
Inside the FDA’s Center Drug Evaluation and Research (CDER) resides the agency’s Drug Shortage Program (DSP). The DSP was established to address potential or actual shortages of drugs that have a significant impact on public health. Through communication, facilitation and negotiation, DSP works with pharmaceutical manufacturers, review divisions, compliance and other components of FDA to manage product shortages.
For example, when the drug shortage is for a generic product (as it often is), the FDA works with other firms making the drug to help them ramp up production if they are willing to do so. Often they need new production lines approved or need new raw material sources approved to help increase supplies. FDA can and does expedite review of these to help resolve shortages of medically necessary drugs.
But the FDA can't require the other firms to increase (or commence) production.
The agency tries to do the best it can with limited authority, spare resources and shared staff. In addition to direct communication with industry, the DSP also gets reports from healthcare professionals, patients/individuals, or professional organizations using the e-mail address drugshortages@fda.hhs.gov.
But, as you can imagine, there is not a lot of e-mail traffic. And there is no social media effort to promote either its purpose or existence.
It’s a good start – but it’s not enough. And you know what they say about good intentions.
The FDA’s Drug Shortage Program is a good start. But it’s not getting the job done. The problem is getting worse. The FDA needs both more authority and greater resources. In short, more needs to happen.
The Institute for Safe Medication Practices reports that, according to survey of 1800 healthcare practitioners, more than half of respondents frequently or always encounter difficulties associated with drug shortages.
The top three problems fall squarely within the zone of appropriate FDA attention and action:
* Little or no information available about the duration of a drug shortage (85%)
* Lack of advanced warning from manufacturers or FDA to alert practitioners to an impending drug shortage and suggested alternatives (84%)
* Little or no information about the cause of the drug shortage (83%)
Survey respondents felt “unsupported by the FDA and are perplexed regarding why the US is experiencing drug shortages of epic proportion that are often associated with third-world countries.”
(More detail on the ISMP survey can be found here.)
And before it becomes a question of American lives.
The EU Innovative Medicines Initiative (IMI), the world’s largest public-private partnership in health R&D, is calling for proposals across seven new health care areas.
The areas of focus are linking patients’ data to develop more targeted therapies; using knowledge management of experimental data for translation into drugs for patients; complications of obesity; predicting Alzheimer’s disease and other dementias; drug delivery by nanocarriers; sustainability of chemical drug production; investigating stem cells for drug discovery; and understanding the behavior of drugs in the human body.
The EU has agreed to contribute up to €105 million ($150 million) to this latest step in IMI's evolution, a figure that will be matched by "in kind" contributions – staff, access to databases and research activity and equipment – from the European Federation of Pharmaceutical Industries and Associations.
The new project phase comes weeks after IMI signed a Memorandum of Understanding with the U.S.-based Critical Path Institute, aimed at increasing collaboration between the two bodies. They have agreed to foster increased information sharing regarding each other’s programs and create a mechanism to exchange knowledge and develop scientific consensus regarding research and testing methods.
But, as our European cousins step up to advancing 21st century medicine, wither our own domestic efforts? What’s become of the Critical Path? Where’s the Reagan/Udall Center?
Funding for the FDA’s Critical Path program and the Reagan/Udall Center is generally considered a “Christmas Tree” issue relative to PDUFA V. That’s a mistake. Beyond the agency’s request to fund it’s Advancing Regulatory Science Initiative (ARSI), we are all talk and no action.
For many involved in the reauthorization process, one statement that keeps coming up is -- ”The FDA is broken.” But what does that mean? Rather than making blanket statements that cause friction and promote areas of disagreement, one thing everyone can agree to is that the FDA’s must be both ally and accelerator in the advancement of innovation.
And that must be within the confines of PDUFA V – and it cannot be accomplished without moving forward the FDA’s Critical Path program and funding the Reagan/Udall Center.
Sander Flaum, the grand master of pharmaceutical marketing asks, “If you put the world’s top CEOs together in a room and asked them what challenges kept them up at night, what do you think you’d hear?”
The answer is shocking if not surprising/
According to the Conference Board’s CEO Challenge 2011 Survey – Fueling Business Growth with Innovation and Talent Development, most CEOs in the U.S. and Europe listed Business Growth as their top challenge.
According to Flaum there’s an even bigger concern. “Look down the list of the top challenges. Where did these leaders consistently rank Innovation? #3! And guess what U.S. CEOs collectively viewed as an even more pressing challenge than the need for innovation– Government Regulation!”
Flaum continues, “A CEO who is more worried about being handcuffed by regulations than coming up with the next big idea needs a priority readjustment. Sure, regulations can be a pain. But they can also be simply an excuse for failure. In Pharma, we’re always contending with the FDA in the struggle to bring innovations to market. And it’s not easy. But doesn’t the need for Innovation come first? If we don’t have something new and important to bring to market, then why complain about the regs?
Top 5 Global Challenges by Region
Rank | U.S. | Europe | Asia |
1 | Business Growth | Business Growth | Talent |
2 | Government Regulation | Cost Optimization | Business Growth |
3 | Innovation | Innovation | Innovation |
4 | Talent Cost Optimization (tied) | Customer Relationships | Corporate/Brand Reputation |
5 |
| Government Regulation | Sustainability |
Wither innovation? This crucial question becomes even more problematic when you consider the issue of “disinvestment” -- the processes of (partially or completely) withdrawing health resources from existing healthcare practices, procedures, technologies, or pharmaceuticals that are deemed to deliver little or no health gain for their cost, and thus do not represent efficient health resource allocation. “Disinvestment” is a more honest (and frightening) term for “comparative effectiveness.”
And leading the disinvestment charge (not surprisingly) is NICE.
Over the past 10 years NICE has identified over 800 clinical interventions for potential disinvestment. But, in the July 27th edition of the British Medical Journal, Sarah Garner and Peter Littlejohns (both of NICE) report that although disinvestment will increase the opportunity for cash saving is unlikely to provide ways of controlling costs without cutting quality of care.
The authors write:
There is general agreement that stretched health services budgets should not be used to fund low value services. However international experience has shown that identifying and removing those services can be problematic and controversial.
Are you listening AHRQ?
Many suggestions for total disinvestment are based on a “social judgment” about whether it is appropriate for the NHS to fund the intervention rather than evidence of poor clinical or cost effectiveness. Others relate to “experimental” use of technologies outside their indications and evidence base.
Are you listening Dr. Berwick?
Opponents of a total disinvestment approach highlight the methodological flaws of using average estimates of effect drawn from populations; they argue that an intervention may be beneficial for an individual patient and should be an option, even if a last resort. An alternative strategy is optimal targeting: identifying subgroups in which an intervention is most clinically and cost effective.
Are you listening Dr. Pazdur?
Disinvestment is part of a broader agenda to improve efficiency and quality focusing on public health and prevention and ensuring that patients receive the right care at the right time in the right way.
Are you listening PCORI?
Although this approach releases resources in the long term, it may entail investment in the short term. It is very important to make the distinction between improving the efficiency of care and saving money.
Aha!
Without data, it is also difficult to identify the subgroups necessary to fully understand variation in care and therefore determine realistic potential savings.
Did somebody say “personalized medicine?” Did somebody say, “more and more targeted molecular diagnostics?”
The author’s conclude, “However, current evidence suggests that disinvestment is unlikely to achieve the huge savings required to meet tightened NHS budgets.”
We would be wise to learn from honesty of our transatlantic cousins.
Avastin Spring helps spur a resistance against bureacracy
By Dr. ROBERT GOLDBERG
Times Guest Columnist
Sometimes, profound change happens so swiftly it’s unrecognized and unappreciated. Such is the case with the response to the Food and Drug Administration advisory committee’s decision to withdraw the agency’s approval for using Avastin to treat metastatic breast cancer.
After the FDA Oncological Drug Advisory Committee declared Avastin to be unsafe and ineffective for women suffering from that incurable form of the disease, the headlines and pundits spun the decision — and the discussion — as one where science triumphed over emotional and desperate women.
Gary Schwitzer, a self-styled expert on objective medical reporting quoted the representative from the National Breast Cancer Coalition who at the ODAC hearing: “This decision can’t be driven by anecdotes. It must be driven by science.”
This is an unfair and lazy characterization of the debate over Avastin. The ODAC panel was stacked with members who already voted against Avastin’s use in MBC. The conflict was over the interpretation of clinical information and whether the FDA can pull an approval because, as it said in December of last year, Avastin doesn’t provide “a sufficient benefit in slowing disease progression to outweigh the significant risk to patients.”
But several other groups that looked at the same evidence came to a different conclusion, including the National Comprehensive Cancer Network and Europe’s equivalent of the FDA, the European Medicines Agency (EMA). Indeed, the EMA expanded approval Avastin based on the same “science” ODAC used in rescinding the drug’s FDA endorsement.
In any event, the speed with which both the Obama administration and private health plans announced they would still cover the cost of Avastin for the use the FDA rejected was stunning. When the FDA decided to yank Avastin’s approval in December 2010, several health plans and regional Medicare reimbursement contractors told women that Avastin would no longer be covered. Such decisions were reversed only after the FDA said it would review its revocation.
Last week, the same organizations — along with the Obama administration — rushed to distance itself from the FDA and assure women it would cover the drug.
The difference in response is a result of the rapid organization of patients through social media. While it culminated in the presence of hundreds of women at the ODAC hearing, that participation was only a part of an extensive, sustained and scientifically informed movement.
The FDA officials and the interest groups urging Avastin’s revocation were outgunned by individual patients who joined together, much as HIV patients did in the 1990s and MS patients did in pushing for the return of Tysabri to the market a few years ago.
This time however, the use of social media to share clinical information, organize support and express opinions was rapid, sustained and, above all surprising. The cancer advocacy “establishment” was outgunned and reduced to irrelevancy. This also happened after the Obama administration recommended not to cover mammograms for women under 50. The National Breast Cancer Coalition sided with the administration — and cancer patients, oncologists and radiologists everywhere told them go stick it.
That decision, like the FDA’s Avastin rendition, is being ignored in practice.
The uprising against the Avastin decision could signal a clear shift in power from the Beltway groups that claim to be patient or consumer “advocacy” groups - but are beholden to a particular party or just staying in favor with the powers that be — to individuals organizing on their own and in their own best interest.
More to the point, such movements are well informed and shaped by what the science says. They are often funding research to accelerate better treatment and detection of illnesses. The attempt to demean or diminish such movements as the expression of anecdotal experience and emotions reflects the arrogance of bloggers and pundits who have but a thimble full of the clinical understanding of the movement’s participants. And it suggests a contempt for any use of social media that does not seek to spread fear or skepticism of innovation.
Most immediately, the Avastin Spring has undermined the legitimacy of the effort to use comparative effectiveness research to delay access or payment for new technologies. Health plans and the government will have to expect ongoing challenges to their ‘expertise’ and claims that it is using the best evidence in determining what to cover. Consumers will be skeptical of one-size fits all judgments made by so-called “experts.”
Similarly, companies who develop new products will have to contend with consumers demanding credible and substantive clinical information.
The Avastin Spring suggests that resistance against bureaucrats telling the rest of us what treatments we can and cannot use will only grow. This is not an anti-science enterprise. Rather, these are movements that regard individual choice as an imperative as the science of personalized medicine advances. It means less authority for those claiming only they have science on their side en route to restricting access to innovations. Both changes bode well for our well being.
Dr. Robert Goldberg is co-founder and vice president of the Center for Medicine in the Public Interest. He is also author of the book, “Tabloid Medicine: How the Internet is Being Used To Hijack Medical Science For Fear and Profit.”
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.
