Latest Drugwonks' Blog
Things are heating up at the CDC.
The agency’s lack of transparency regarding their development of opioid prescribing guidelines has drawn the attention of the House Committee on Oversight and Government Reform.
In a letter to CDC Director, Dr. Tom Frieden both the Chair, Representative Jason Chaffetz (R, UT) and Ranking Member, Representative Elijah Cummings (D, MD) share their displeasure at the secretive nature of the guideline development process. Per the Committee, “We have questions about why a Core Expert Group established by CDC to assist with drafting these guidelines is not considered an advisory committee under the Federal Advisory Committee Act (FACA).”
Those questions and an aggressive documents request are included in the letter which can be found here. And the Committee wants them by January 8th. Looks like there will be some people called back from their Christmas vacation at the CDC.
Perhaps the best way to address the CDC’s fairy tale process is to quote from author of Peter Pan:
“Those who bring sunshine into the lives of others cannot keep it from themselves.”James Barrie
President Obama Signs Off on Omnibus Bill Upping FDA’s Funding
President Barack Obama signed into law on Friday the fiscal 2016 omnibus spending bill, which contains $4.68 billion in total funding for the FDA.
Congress had wasted no time approving the measure Friday morning, as it sailed through both chambers by wide margins.
The bill – which includes more than $2.7 billion in discretionary funding, a $132 million increase from the previous year – passed the House and the Senate by margins of 316 to 113 and 65 to 33, respectively.
Industry insiders have touted the bill as a positive for the FDA. “[Congress] is beginning to recognize that the FDA, to do its job, needs appropriate funding to be an innovator,” Peter Pitts, president and founder of the Center for Medicine in the Public Interest and a former FDA associate commissioner, tells DID.
Ladd Wiley and Steven Grossman, executive director and deputy executive director, respectively, of the Alliance for a Stronger FDA, describe the funding in a prepared statement as a “victory.” They add that the distribution of funds appears to largely mirror the priorities of the administration’s request.
New technologies that support postmarketing patient communication and safety surveillance can produce a mountain of data. But are these new tools creating value or just more noise?
YourEncore recently convened a panel of experts to discuss this topic after the 2015 Regulatory Affairs Professional Society (RAPS) Convergence conference in Baltimore, Maryland. To watch the panel discussion, click here.
YourEncore Executive Partners, Peter J. Pitts, former FDA Associate Commissioner, and Dr. Don Therasse, former VP of Global Patient Safety and Global Medical Affairs at Eli Lilly & Co., shed some light on the topic.
Peter Pitts: There is no such thing as a risk-free product. From a regulatory perspective, when you’re looking at outcomes, we’re learning the difference between efficacy in a clinical trial and effectiveness in the real world and how to capture and compare the data sets.
The general consensus is that MedWatch captures around 10 percent of adverse events. That’s probably high. But even if it’s spot on, it’s remarkably and dangerously low. How are we capturing and reporting substandard pharmaceutical events when a drug doesn’t necessarily have an adverse event but just isn’t working? API problems, excipient problems, manufacturing problems—from a lexicon perspective, unless you can put a name to it and put systems in place, it’s anecdotal. If we want to bring drugs to market faster with truncated clinical trials, we’re going to need a much more robust post-marketing proposition.
There are a lot of ways to collect data. Social media is one that has caused problems. The signal to noise ratio issues are profound, but we can’t ignore it because within all that noise there are gems that we must capture. The challenge is how to put robust modern pharmacovigilance or pharmacoepidemiology programs in place for established drugs and decide who leads the effort. We need to do a better job of capturing and sharing data in real time. This requires better staffing and an openness to finding new things.
A couple of years ago I was talking to a pharmaceutical company in New Jersey, and someone said to me, “We don’t use social media because we don’t want to find adverse events.” We must embrace negative information, because it’s happening in the real world.
Don Therasse: Everybody talks about how we can do these things and manage the entire post-approval safety environment more effectively and efficiently. The fear is not that we will find new information; it’s that we would overwhelm our current systems and capacity with poor quality information – and just generate more noise as opposed to real signals. That’s the primary concern about the social media space.
The goal of the pharmacovigilance enterprise is not to simply generate more signals; it’s to generate better signals and to apply our finite resources to identifying safety issues and implementing programs to help mitigate them. In terms of regulatory convergence, or divergence in this area, we need work not only in this and other areas that define sources of information for signal detection, but also for how we manage the data, how it’s reported, how you’re inspected and how you implement your risk mitigation programs. Everybody has the same goals, but everyone seems to want to put their own spin on it which causes redundant effort and diverts way too many resources from the important work at hand creating a very inefficient system.
There are many good ways to advance the science. At the same time we have to be disciplined and willing to give up older, less effective activities. There are finite resources on both industry and regulatory sides, and we’re diverting too much of our attention to nonproductive activities at the expense of fully implementing powerful new tools.
Pitts: We have a tool at our disposal that is poorly used, which is physicians. How many hours do medical students spend learning about drug safety management and adverse event reporting? None. How much time do physicians spend in their daily practices thinking about adverse event reporting? How friendly is the MedWatch system? Obviously, the first mission of doctors is to address their patients’ immediate needs. Once that’s done there is an obligation to share information that can advance the science and ultimately help to prevent similar issues for future patients. We need greater awareness and more effective, user-friendly processes to encourage and enable them to do so.
To paraphrase Homer Hickam (of "October Sky" fame), “A docket won't fly unless somebody lights the fuse.”
Here are my comments to the CDC’s docket Proposed 2016 Guideline for Prescribing Opioids for Chronic Pain:
In determining appropriate guidelines, CDC should engage as part of an intramural HHS team. FDA has issued labeling changes for this category along with thoughtful and strategic roadmaps for how and why they can be successfully implemented. The FDA’s statements and actions on the approval, labeling, and future development of abuse-deterrent products and technologies are designed to both protect and advance the public health relative to the balance of benefit/risk and access. Further, FDA has identified prescriber, dispenser, and user education as a major focus for pursuing a safe-use agenda for opioids. CDC must broaden its vision when it comes to the development of opioid guidelines to include the thoughtful, dynamic, patient-focused programs already instituted by the U.S. Food & Drug Administration.
From the fine folks at RAPS:
CDER’s Woodcock Outlines Priorities for 2016
With a banner year for new drug approvals under its belt in 2015 (42 approvals and counting), the US Food and Drug Administration’s (FDA) Center for Drug Evaluation and Research (CDER) is now looking at how it can not only negotiate three new user fee agreements but fill an enormous number of staff vacancies.
CDER Director Janet Woodcock, speaking Monday at the FDA/CMS Summit in Washington, DC, outlined 2015’s achievements and a number of the agency’s top priorities for 2016, particularly as CDER, with its $1.2 billion budget, continues to work with Congress on legislation like the House-passed 21st Century Cures Act.
As far as meeting CDER’s priorities for 2015, Woodcock said the agency did “pretty well,” noting that there were some serious concerns in the year prior on addressing the backlog of abbreviated new drug applications (ANDAs), though she said there’s been “a huge turnaround.”
FDA has been particularly interested in reducing the number of multiple cycle reviews for generic drugs, she said, noting that in the not-too-distant past the average was four review cycles, though the reduction in such cases has occurred over the past year as more companies understand what it takes to submit a complete ANDA.
John Jenkins, Director of the Office of New Drugs at CDER, also outlined a number of the drug approval statistics, particularly as CDER has seen a steep rise in orphan drug approvals, though he noted that such approvals aren’t always to the benefit of public health (some of his slides can be viewed here).
On the international front, Woodcock highlighted FDA’s work with the International Conference on Harmonisation (ICH), noting that it “was headed off a cliff,” though after “strenuous efforts,” FDA was able to help sign new agreements and make the group more inclusive, which should be a boon for negotiating more global standards for drugs.
And while many in Congress and industry are still waiting on new biosimilar draft guidance documents on labeling and interchangeability, among others, Woodcock said that CDER has been working extremely hard behind the scenes to ensure the US market for biosimilars can be robust in the near future as education efforts continue.
She also highlighted the success of the new “drug trials snapshots” program under CDER, which offers a look at the demographics of clinical trial data for newly approved drugs, which she said has been “very popular” for consumers.
A Look Ahead
As far as what to expect for 2016, Woodock offered a wide-ranging laundry list of topics that the agency will look to address, though the 680 vacancies at CDER seem to be one of the focal points.
The re-negotiations of the prescription drug, generic drug and biosimilar user fee programs will also be at the forefront of CDER’s work next year as these agreements with industry need to be ironed out before the programs expire in 2017.
In addition, CDER is looking to:
- Reevaluate the regulations on drug advertising and promotion in light of current jurisprudence around the First Amendment
- Issue draft guidance on generic versions of abuse-deterrent opioid formulations
- Integrate the Sentinel Network into routine drug safety activities
- Further implement statutory provisions on track and trace legislation
- Continue drug label improvement initiative as “a lot of labels are out of date,” Woodcock said
- Develop a more robust process and policy documents on how to evaluate a biomarker as a surrogate endpoint for accelerated approvals
- Streamline clinical trial monitoring and data cleaning practices
- Conduct more outcomes assessments of breakthrough therapies, modernize clinical evidence assessments and further utilize electronic health data (which Woodcock said is a priority for FDA commissioner nominee Robert Califf)
- Make significant progress on FDA’s mutual reliance initiative with the European Medicines Agency
- Improve combination product inter-center review process
- Develop an implementation plan and training for a new pregnancy/lactation labeling rule
- Continue to push standards development and standardized electronic submissions to CDER
From the pages of Politico:
CDC opens opioid prescription guidelines to public comment
The CDC plans to publicly post draft guidelines on opioid prescribing after being criticized by pain advocates, professional associations and some within HHS for developing them behind closed doors and with limited public input.
A notice posted this morning provides 30 days for public comment, which means that the guidelines - a key part of the Obama administration's response to the opioid abuse and overdose epidemic - won't be released in January as the agency had planned.
"Opening a docket will tack months on to the process [and also] increases the likelihood that the guideline may never be released," said Andrew Kolodny, a founder of Physicians for Responsible Opioid Prescribing and the chief medical officer at Phoenix House. "This is an enormous win for the opioid lobby."
CDC hadn't planned to publish the document ahead of its release in January but came under fire earlier this month from members of the administration's Interagency Pain Research Coordinating Committee, which announced that it would file a formal objection to CDC's prescribing guideline after agency officials briefed them at a meeting.
The level of evidence cited to support the guidelines, which are non-binding on physicians and apply to chronic pain patients outside of the cancer or palliative care treatment, "is low to very low and that's a problem," Sharon Hertz, FDA's director of the Division of Anesthesia, Analgesia and Addiction Products, said at the meeting.
AHRQ health scientist Richard Ricciardi, another member of the interagency committee, called the recommendations "ridiculous" and "an embarrassment to the government."
The document had already been circulated among HHS agencies for final review ahead of its planned release in January, but it had drawn criticism from the American Cancer Society Cancer Action Network and the American Medical Association after it was previewed for some health care groups at a webinar in September.
CDC didn't immediately respond to a request for comment.
I’ve been a good policy wonk this year, so here’s my FDA wish list for 2016 …
· Thoughtful guidance on differential nomenclature for biosimilars that recognizes that “similar” doesn’t mean “identical” and prioritizes the need for savvy pharmacovigilance
· Further agency thinking on biosimilar label extrapolation
· Physician notification x 50 states, Puerto Rico, and the District of Columbia (not under FDA authority -- but since we're on the subject)
· 21st century bioequivalence written guidance for generic drugs (including tighter ranges for narrow therapeutic index medicines and critical dose drugs)
· A super effort from the FDA’s new Super Office of Pharmaceutical Quality
· Aggressive intramural efforts on biomarker development and validation
· A first quarter meeting on off-label communications
· Smart efforts on abuse-deterrent opioid PROs
· Next-step traction for Patient-Centered Drug Development
· More attention to combination products
· And IVDs
· Continued sophisticated thinking (from management) – and action (on the Division level) on adaptive clinical trials
· Completion of the Generic Labeling Rule
· Better oversight of compounding pharmacies
· And drug shortages
· For-real updating of the PMA and 510k processes
· Continued sanity on drug importation
· And medical mobile apps and social media
· Sharper teeth on dietary supplements
· 21st Century Cures legislation with both mandates and budget
· A standardized benefit/risk analysis grid
· Wider lanes on expedited pathways
· A potent PDUFA that recognizes that FDA resides at the center of the precision medicine ecosystem.
· A potent PDUFA that doesn’t use “fast and clean” as it’s sole metric for success.
· A swift, positive vote for Rob Califf
And Santa, this is only a partial list.
Nothing was said about how, after pocketing those discounts (a Credit Suisse report estimates that $90 billion is handed over to these entities each year) many of the drugs, let alone the discounts, are available to consumers. And nothing was said about how drug companies are in fact negotiating and involving health plans with data about the long term value of products years before a drug is approved. Or that, PBMs and AHIP launched a cynical campaign to blame drug companies for the high costs that they were in imposing on consumers that was paired by an concerted effort to hike the cost of more and more medicines to patients even as they were pocketing rebates
Scott Gottllieb wrote an excellent article in Forbes descrbing how this affects patients with MS:
"I examined the plans marketed in the state’s most populace county, selecting the median-priced Silver plan offered by each carrier in that market. I examined how the plans covered the 12 leading oral and injectable drugs for treating multiple sclerosis. What I found was discouraging.
All of the plans were closed formularies. None of the plans provided even partial coverage for all of these drugs. That means that for each plan, certain patients would be forced to foot the entire bill for their medicine. What patients spent wouldn’t count against their deductible or out of pocket limits. One of the insurance plans covered 11 of the drugs; three of the plans covered 10 of the 12 drugs; and four of the plans covered only nine of the drugs. Aetna AET +0.96%, on the whole, was the best insurer.
Of the remaining 12 health plans; three covered just eight drugs; three covered only seven drugs; and another three covered just six of the drugs used to treat Multiple Sclerosis. Of the remaining two health plans, one of the plans only provided coverage for four drugs; and the final plan provided coverage for just three of them.
In almost all cases, when the plans did cover these drugs, they put these medicines on their fourth or fifth drug tiers, meaning that consumers were saddled with high co-insurance and would, in most cases, end up maxing out their deductibles and hitting their out of pocket limits (which averaged more than $13,000 across the different plans. This spending would come on top of what people paid in premiums)."
The Affordable Care Act has had the unintended conseuence of forcing payors and PBMs to screw sick patients to stay afloat financially. Similarly, drug companies have cut deals with PBMs to exclude any number of medicines in exchange for deep rebates. In some cases, such as psoriasis and psoriatic arthritis, patients are being denied access to safer new medicines and being forced to try other drugs that have more side effects.
This is insane. Long term, every company in the business of helping patients get better needs to devote more time and effort to providing the most effective treatment for each patient. And we need to continue to reduce the time and cost required to develop new medicines.
We need precision medicine. And fast.