Latest Drugwonks' Blog
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.
From the pages of insidesources.com ...
New Compounded Drug Renews Safety Concerns
Last week, Express Scripts announced it would begin processing prescriptions for Imprimis Pharmaceuticals’ drug compound for patients suffering from toxoplasmosis in response to a recent price hike by the makers of the only FDA-approved medication for toxoplasmosis, Daraprim.
“We believe we now have a safe, high-quality and extremely cost-effective way to provide access to a Daraprim alternative,” said Dr. Steve Miller, Senior Vice President and Chief Medical Officer of Express Scripts, one of the country’s largest pharmacy benefit managers (PBM) with over $100 billion in annual revenue.
But the safety and efficacy of compounded drugs have raised questions in the healthcare community and among regulators, and at least two of Imprimis’ compounding facilities have been cited by the FDA for Common Good Manufacturing Practices (CGMP) violations.
Back in 2012, a meningitis outbreak that sickened more than 700 people and killed at least 50, was traced to a compounding facility in Massachusetts setting off a wave of heightened concern and regulatory oversight. Separately, Imprimis’ facilities in New Jersey and Southern California (July 2014 and June 2015) have been issued letters from the FDA citing violations that could call into question the safety and efficacy of the drugs compounded there.
Imprimis says that they did not own the facilities at the time of the violations. The California facility was acquired earlier this year and has not yet been reinspected. The New Jersey facility was inspected in September, and Imprimis says there were “three minor observations noted on the report, all of which have been responded to with no further comments from the FDA.”
But Peter Pitts, former FDA associate commissioner and president of the Center for Medicine in the Public Interest, expressed concern, “just because a facility changes ownership doesn’t mean that existing quality problems can be discounted.”
In testimony before the House Energy & Commerce Committee, Dr. Scott Gottleib, resident fellow of the American Enterprise Institute, said that compounded drugs let “physicians customize drugs to individual patients,” noting that “traditional pharmacy compounding is performed on a small scale.”
According to the FDA’s website, compounded drugs are not generally approved by the FDA and therefore the “FDA does not verify the safety, or effectiveness of compounded drugs.” Additionally, the FDA warns, “[t]here can be health risks associated with compounded drugs that do not meet federal quality standards. Compounded drugs made using poor quality practices may be sub- or super‑potent, contaminated, or otherwise adulterated. Additional health risks include the possibility that patients will use ineffective compounded drugs instead of FDA-approved drugs that have been shown to be safe and effective.”
When Congress passed a new law in 2013 that provided the FDA with greater authority over compounding facilities, Dr. Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research, expressed some concern that the law didn’t go far enough. “While the new law doesn’t provide the FDA with all the additional authority it sought, these provisions are definitely progress,” she said.
Now with this latest announcement from Express Scripts, Imprimis is set to provide patients a compounded drug comprised of two FDA-approved drugs, pyrimethamine (the active drug in Daraprim) and leucovorin, even though the two have never been approved by the FDA to be used together.
The president of research and development for the manufacturer of Daraprim, Turing Pharmaceuticals, Dr. Eliseo Salinas said, “Daraprim remains the only FDA-approved treatment for toxoplasmosis encephalitis when used conjointly with a sulfonamide. Patients and physicians are likely to assume the compounded product is as safe and effective as the FDA-approved drugs pyrimethamine and leucovorin, even though its safety and efficacy profile is unknown.”
Mark Baum, the CEO of Imprimis, questioned that characterization. “The idea that FDA is not involved in nearly the entire drug supply chain of what is produced by our company is just simply not true.” He says the partnership with Express Scripts speaks to the safety of their practices. “Express Scripts is not going to partner with a company that does things the wrong way,” explains Baum. He says Imprimis is now in talks with other leading PBMs, and these companies won’t partner with a compounder that is putting patients at risk.
Pitts, offered words of warning for doctors treating patients with compounded drugs. “Physicians are not pharmacologists. They do not take medical school courses in drug compounding. And since this is not their area of expertise, they should not be deemed ‘experts’ and asked to make a therapeutic choice.”
He added, “the FDA approves innovator and generic medicines based on the benefit/risk/quality equation. It’s a dangerous precedent for a PBM [Express Scripts] to decide on its own to use cost as the sole factor in reimbursement policy. It is irresponsible at best and dangerous at worst.”
There also remains some question as to the legality of Imprimis distributing its unapproved compounded drug widely. Gottleib, who many consider a potential nominee for senior FDA position should a Republican win the White House, said later in his testimony, “but once pharmacies begin manufacturing and shipping medicines on a wide scale, and do so in a way that isn’t in response to a valid prescription, these firms often become ‘drug manufacturers’ and fall squarely under the FDA’s extensive authority.”
A spokesperson for the FDA declined to comment when asked about the Express Scripts-Imprimis announcement and the use of a compounded drug when an FDA-approved drug is available.
Baum argues that an unintended consequence of current policy is to encourage drug companies to engage in monopolistic behavior for some drugs that have no generic competitor, in part because it is so difficult to get new drugs approved by the FDA. “I really believe the future of compounding is in 503B outsourcing facilities. It is in making as many drugs that are compounded as possible,” Baum said.
However, Pitts, the former FDA associate commissioner, said: “The way to drive prices down is not to promote the unapproved use of unapproved compounded medicines. A more effective route is to inject competition into the marketplace. Competition, in this case, coming from additional FDA-approved generic pyrimethamine products.”
Perhaps such Partners for Better Care is such a movement. The organization has 6 objectives. Most important (at least in my opinion) is this statement:
"We believe patients should have access to adequate formularies that do not discriminate against any medical conditions and ensure patients have affordable access to prescription drugs, devices, and other therapies. Tiering and pre-authorization limitations are becoming more common in formularies, and problems persist with access to devices and allied health professionals such as physical therapists."
I am not usually a joiner beyond my shul and gym. But I just joined PBC. You should too.
It's not that Congress won't pass the bill. It's just that it, by letting the act expire, have demonstrated an indifference to suffering and terror. Talk is cheap.
Meanwhile, Jon Stewart has been leading the effort to get the legislation renewed ASAP. He returned to The Daily Show to cajole Congress into taking action with humor and genuine outrage
Stewart asked viewers to contact congress on social media with the hashtag, "#WorstResponders."
"People forget, with all this talk now about terrorism from the World Trade Center to San Bernardino, the one common link to all of this is the first people on the scene were first responders," Stewart said. "What message does it send to our first responders if once we're done as a nation with them helping us that we forget about them? That's unacceptable to me."
So it should be for us all!
FDA Postpones Generic Drugs Safety Update Rule Again
Drug Industry Daily
After pushing a proposed patient safety rule back yet again, the FDA has received criticism for putting patients at risk.
The rule - which would empower generic drugmakers to update labeling to provide warnings about newly discovered risks to patient safety without prior FDA approval - now is expected to be final in July 2016, after being delayed several times following its proposal in 2013.
Under current FDA regulations, NDA and BLA holders are permitted to make safety updates without agency approval, but generic drugmakers cannot do so unless instructed to by the FDA.
Public Citizen's Health Research Group described the postponement as a "safety gap" for patients who take generic medications.
"The agency should resist pressure from the pharmaceutical industry and finalize a rule that will protect patients," says Michael Carome, director of the Public Citizen Health Research Group.
GPhA and PhRMA are pushing an alternate plan that would make the FDA the central arbiter of all labeling changes - for NDA and ANDA holders alike - once the first generic version hits the market (DID, May 27).
Peter Pitts, president and founder of the Center for Medicine in the Public Interest and a former FDA associate commissioner, also has underscored the importance for such a rule, noting there have been several high-profile recalls of generic drugs because they did not deliver the outcome they were supposed to.
"How can you communicate the fact that bioequivalent does not mean identical?" Pitts rhetorically asks.
Pitts, however, notes that the rule would be a significant addition to the Food, Drug and Cosmetic Act, and would need to be carefully worded legally. He tells DID that his educated guess for the postponement of the rule is because of the high volume of comments being examined from a legal perspective.
From the pages of Politico:
HHS split on CDC opioid prescription guidelines
A panel set up to coordinate pain research across the federal government is blasting a CDC proposal to rein in opioid prescribing set for release next month.
Members of the NIH's Interagency Pain Research Coordinating Committee, which was created by Obamacare and includes the FDA, AHRQ and the Department of Veterans Affairs, announced at a meeting Thursday that they plan to file a formal objection to the CDC prescribing guidelines. Those guidelines are a key piece of the administration's effort to combat the prescription overdose epidemic that claims more than 16,000 lives a year.
The level of evidence cited to support the guidelines, which are non-binding on physicians, "is low to very low and that's a problem," said Sharon Hertz, FDA's director of the Division of Anesthesia, Analgesia and Addiction Products.
AHRQ health scientist Richard Ricciardi called the recommendations "ridiculous" and "an embarrassment to the government."
The dissension within HHS adds to a chorus of complaints from both the pain community and major medical groups including the American Medical Association and the American Cancer Society Cancer Action Network, which have criticized CDC's selection of experts and the limited opportunity for public input on the guidelines. CDC has not released a draft but an early version has circulated.
Wanda Jones, principal deputy assistant secretary for health at HHS, told the interagency committee members that they should still register objections, even though time is running out. She said the CDC process had been "shortsighted" and rushed. "You know, damn the torpedoes. Full speed ahead."
Jones is not a member of the NIH committee but provided an update on the National Pain Strategy.
Several committee members were frustrated that the response to the opioid epidemic appeared to trump a broader effort underway to develop an integrated strategy to combat pain and could in fact hinder it by limiting access to certain necessary drugs.
"We have both a pain and an opioid use disorder problem. Both are important. Both are serious," said Richard Frank, HHS assistant secretary for planning and evaluation.
CDC did not respond to a request for comment.
CDC policy official Sara Patterson told the interagency group by conference call that the guidelines' three main goals are to have providers prescribe non-opioid options for pain when possible; to use the lowest effective dose when opioids are necessary, and to actively evaluate the risk and potential harms of ongoing treatment. The CDC is not recommending any changes in the role of opioids in treating cancer pain for palliative care.
Each category has a number of specific guidelines, and many are characterized as a "strong recommendation" with "low evidence" or "very low evidence" because of the lack of randomized control trials. Patterson said that they were supported by an exhaustive literature review, however, including a 2014 AHRQ review of "The Effectiveness and Risks of Long-Term Opioid Treatment of Chronic Pain."
AHRQ found scant evidence that opioids control chronic pain and that long-term use had serious risks. Deaths from prescription painkillers have quadrupled since 1999, according to the CDC, topping 16,000 in 2013. Nearly 2 million Americans either abused or were addicted to the drugs that year, the agency estimates. In 2012, health care providers wrote 259 million prescriptions for the drugs - enough for every American adult to have a bottle of the pills.
Patterson emphasized that the guidelines would be "non-regulatory" - meaning non-binding - and that the CDC "stands by" them.
The CDC effort is part the Obama administration's efforts to combat the epidemic, including expanding access to overdose antidote naloxone, making medication assisted addiction treatment more available, and improving state prescription drug monitoring programs.
John McCain has always supported drug importation “from Canada.” And he has been wrong every time.
He has resurrected his effort (via Amendment SA 2884) and cites the Turing Pharmaceuticals example, “"Don't you feel when people are paying $750 for a pill that maybe they ought to be able to go to Canada and buy one that's reasonably [priced]?”
Note to Senator McCain –the Turing product is an off-patent drug but there isn’t any generic competition. And that’s important because generic drugs are less expensive in the US than in Canada. The way to drive down the prices of single-manufacturer off-patent drugs isn’t to import foreign price controls -- it’s to inject healthy competition into the equation by making it worthwhile for multiple manufacturers to offer products like Turing’s infamous Daraprim.
As to the broader arguments against drug importation – here we go again.
Importing drugs from Canada is exceedingly dangerous for a number of reasons. For starters, many Internet pharmacies based up north are stocked with drugs from the European Union. And while many wouldn’t hesitate to take medicines purchased from countries like France and Great Britain, there’s plenty of risk involved.
The EU currently operates under a system of “parallel trade,” which allows products to be freely imported between member countries. This means that any drugs exported from the U.K. to Canada could have originated in an EU country with significantly less rigorous safety regulations like Greece, Portugal, Latvia or Malta.
Just last year, EU officials seized over 34 million fake pills in just two months. And in May, Irish drug enforcers confiscated over 1.7 million pounds of counterfeit and illegal drug packages. So if American customers start buying drugs over the Internet from Canadian pharmacies, they could easily wind up with tainted medicines of unknown European origin.
It’s also important to note that drugs from anywhere in Europe aren’t even legal for sale in Canada. So when politicians say we can get “the same drugs” that Canadians get, they’re just plain wrong.
Even more worrisome is outright fraud — many “Canadian” pharmacies are actually headquartered somewhere else.
A 2005 investigation by the Food and Drug Administration looked at 4,000 drug shipments coming into the U.S. Almost half of them claimed to be from Canada. Of those, a full 85 percent were actually from countries such as India, Vanuatu and Costa Rica.
As part of another investigation, FDA officials bought three popular drugs from two Internet pharmacies claiming to be “located in, and operated out of, Canada.” Both websites had Canadian flags on their websites. Yet neither the pharmacies nor the drugs were actually from Canada.
As an FDA official told Congress, “We determined there is no evidence that the dispensers of the drugs or the drugs themselves are Canadian. The registrants, technical contacts, and billing contacts for both web sites have addresses in China. The reordering website for both purchases and its registrant, technical contact, and billing contact have addresses in Belize. The drugs were shipped from Texas, with a customer service and return address in Florida.” And in laboratory analysis, every pill failed basic purity and potency tests.
The on-the-ground reality of state and local importation schemes has been dismal and politically embarrassing. Remember Illinois’ high profile “I-Save-RX” program? Over 19 months, only 3,689 Illinois residents used the program—that’s .02 percent of the population.
And what of Minnesota’s RxConnect? According to its latest statistics, Minnesota RxConnect fills about 138 prescriptions a month. That’s in a state with a population of 5,167,101.
Remember Springfield, Massachusetts and “the New Boston Tea Party?” Well, the city of Springfield has been out of the “drugs from Canada business” since August 2006.
And speaking of tea parties, according to a story in the Boston Globe, “Four years after Mayor Thomas M. Menino bucked federal regulators and made Boston the biggest city in the nation to offer low-cost Canadian prescription drugs to employees and retirees, the program has fizzled, never having attracted more than a few dozen participants.”
The Canadian supplier for the program was Winnipeg-based Total Care Pharmacy. When Total Care decided to end its relationship with the city, only 16 Boston retirees were still participating.
Programs like this wouldn’t do any better on a national basis. A study by the non-partisan federal Congressional Budget Office showed that importation would reduce our nation’s spending on prescription medicines a whopping 0.1 percent—and that’s not including the tens of millions of dollars the FDA would need to oversee drug safety for the dozen or so nations generally involved in foreign drug importation schemes.
Calling foreign drug importation “re-importation” is a clever way to sell the idea to the American people. But the term simply doesn’t fit with the facts. In reality, in addition to importing foreign price controls, Americans would end up jeopardizing their health by purchasing unsafe drugs while not saving money.
McCain acknowledged that similar efforts to legislate drug importation had fallen short many times in the past, but said, "sooner or later, even pigs fly.
Think again, Senator McCain.
He claims that drugs are the “only major category of health care services for which the producer is able to exercise relatively unrestrained pricing power.” He states that “by law, drug manufacturers can set the price that Medicare and Medicaid programs pay for new drugs, and they also benefit from significant negotiating advantages over private insurers, who are required to cover most new drugs and are unable to obtain significant price concessions from manufacturers, particularly for drugs that offer some clinical advantage or use alternative mechanisms of action compared with available treatment options. As a result, drug prices in the United States are generally 2 to 6 times higher than prices for the same drugs in other major industrialized nations.
These statements are incorrect and the assertion that free market pricing leads to high drug prices in the United States compared to “other major industrialized nations” is largely untrue.
Like every other health care good and service, drug prices are negotiated by private insurers and government health programs. Bach’s description of Medicare and Medicaid’s approach to drug prices also characterizes how wheelchair and hip replacement prices are established.
The average discount of off the Average Wholesale Price (a sticker price if you will) is anywhere from 10-50 percent on new medicines. Those discounted prices are about the same as the prices listed by health systems in Germany, UK, Canada, etc. The negotiated price for Solvadi in Germany is $46625. In France, it’s $51000.
In the United States? The government programs got a 65% discount. That’s $30000. Private health plans received a 40 percent discount. That’s $50000.
Bach usually fails to ask if these discounts ever make it to the patients that will be using the drugs. This, from someone who raised the same question about hospitals marking up drugs discounted for poor patients and re-selling them at a huge markup.
Some of the biggest health plans take the discounted drugs and then require patients to pay up to 50 percent of the cost of the drug. The drug price we see is therefore set by PBMs and insurers. And it is never the price they get the drug for in the first place.
Bach never questions the morality of such business practices. Indeed, he has successfully avoided answering an inconvenient question: If new drugs for cancer, heart failure, Hepatitis C etc. are en route to bankrupting America, why are they only 2 percent of the total insurers spend on health care each year. Bach’s false assumptions are designed to divert attention from this fact. And to justify a proposal that would give PBMs and insurers even MORE control over access to new medicines and their prices.
Bach and his co-author Steven Pearson have produced an interesting variation of value-based health insurance design. The would reduce out of pocket cost sharing for drugs that work or benefit patients, extend patent protection to those that demonstrate value in new patients with other illnesses and discourage use of medicines that don’t work.
That sounds sensible. However, Bach and Pearson would impose this value-based design on patients. And who would define value? The payors and PBMs who pocket rebates, re-sell discounted drugs to patients for a profit, force patients to pay a share of the marked up price for drugs they need and use cost sharing and fail first programs that make people sicker and ultimately discourage patients from enrolling in their plans in the first place
In fact, Bach and Pearson’s approach – a one size fits all value that gives PBMs and insurers to cut deals and design drug plans that maximize profits at the expense of the sickest patients -- would legitimize this questionable and counterproductive practices.
In the absence of dramatic reductions in the time, cost and uncertainty associated with developing new medicines for smaller groups of patients, prices will be what they are.
The best way to reduce the cost of health care is to insure that more people get the treatment best for them the first time. We have the ability to customize treatments to patients and replace large upfront costs with long term financing for many medicines. We are barely using precision medicine tools that would enable such a patient-driven approach. And what we learn from these new approaches can be used to improve medical care and make it more predictive, prospective, personalized and participatory. But Bach and Pearson ignore these tools.
Hence, the value based approach to drug pricing as proposed by Bach and Pearson institutionalizes the marginalization that sustains many (but not all) PBMs and insurers. Value-based drug pricing is nothing more than the health care policy way to pretend that separate and equal is not discrimination.