Latest Drugwonks' Blog
At Barnes-Jewish Hospital, Dr. Lynch said physicians from all over the Midwest referred their sickest heart patients to his facility for transplants and other major interventions. But those patients can skew his hospital’s readmissions numbers, he said: “The weaker your heart, the more advanced your emphysema, the more likely you are to be readmitted to the hospital.”
Dr. Lynch said Barnes-Jewish set up follow-up appointments for patients who didn’t have their own doctors. But about half of the patients never showed up, he said, even after the hospital made reminder phone calls and arranged for free rides. Sending nurses to see patients at home did not significantly reduce readmission rates either, he said.
“Many of us have been working on this for other reasons than a penalty for many years, and we’ve found it’s very hard to move,” Dr. Lynch said. He said the penalties were unfair to hospitals with the double burden of caring for very sick and very poor patients.
“For us, it’s not a readmissions penalty,” he said. “It’s a mission penalty.”
Read the full New York Times piece here.
The first step towards solving a problem is to identify that a problem exists.
The breakthrough therapy provision in FDASIA is aimed at shortening the development time for drugs intended to treat serious or life-threatening conditions and for which preliminary clinical evidence suggests a substantial improvement over existing therapies. But the devil is in the developmental details.
But the promise of speeding innovative medicines to market could be blunted unless issues related to manufacturing, companion diagnostics and international harmonization are adequately addressed.
That was the message from a multi-stakeholder panel discussion at the November 14th Conference on Clinical Cancer Research, co-sponsored by the Friends of Cancer Research and the Engelberg Center for Health Care Reform at Brookings.
Panelists and FDA representatives agreed that if a drug is ushered through the development process, hold-ups will arise from other areas. As a result, discussions surrounding chemistry, manufacturing and control issues for new drugs and biologics will need to take place much earlier in the clinical development process than currently happens to avoid a situation where a breakthrough therapy is approved but the manufacturing processes are not in place to support commercial marketing.
Discovery is one thing. Development and commercialization are another. Nobody said it was going to be easy.
Breakthrough treatments that require companion diagnostics also could be potentially problematic, as the development, validation and approval of the diagnostic may not be able to keep pace with the drug’s abbreviated clinical development program.
Under FDASIA, sponsors must request that their product be designated as a breakthrough therapy, and FDA must respond within 60 days. For drugs receiving the designation, the agency must work in a variety of ways to expedite the products’ development and review, including providing timely advice to the sponsor to ensure the development program is as efficient as possible and involving senior managers and experienced review staff in a collaborative cross-disciplinary review.
Under the law, FDA must issue draft guidance by January 2014 on the process and criteria for making designations and actions the agency will take to expedite development and review.
What about international harmonization? During the development of the FDASIA legislation, Woodcock cited the need for FDA and EMA to “be on the same page” about abbreviated development programs for breakthrough therapies. And, according to a conference issues brief, absent an equivalent development pathway in the EU, “drugs that receive breakthrough designation in the U.S. may still be required to go through the traditional drug development pathway for EMA approval. These differing requirements may make the breakthrough pathway an unattractive option for drug sponsors.’
Richard Pazdur raised the question as to what happens when subsequent studies of a breakthrough-designated product fail to confirm the encouraging efficacy signal seen early in development. Bob Temple suggested the agency’s guidance on breakthrough designations would account for such a scenario. “The concept clearly includes the possibility that it looked really good at first and then now it doesn’t and so it’s designation could go away,” he said. “I’m sure there will be a provision for that.”
That's one thing we can most certainly be sure of. Caveat emptor.
“PR” does not stand for “Post Regulatory” – nor should it.
Via an untitled letter concerning a pitch letter, the FDA sent out an important holiday reminder that press materials are, indeed, regulated speech.
The target of the October 31st letter was Cornerstone Therapeutics. Their press release for its Curosurf (indicated for rescue treatment of premature infants experiencing Respiratory Distress Syndrome) was, according to the FDA, false and misleading due to omission of risk info and presentation of unsubstantiated superiority claims. A pretty standard objection, and an obvious mistake that should have been avoided by the Cornerstone communications staff.
Communications departments and PR agencies beware – play by the rules or suffer the consequences.
The Problem of Fake and Useless Drugs
Global health authorities are making only fitful progress toward eliminating fake or substandard drugs that cause widespread suffering and death in the developing world. Delegates from 76 member countries of the World Health Organization met this week in Buenos Aires to lay the groundwork for more forceful action.
No one knows precisely how much fraudulent or substandard medicine is sold around the world, but the fragmentary data are alarming. In poor countries, half of the medicines used to treat some deadly diseases have been found to be fakes that had little or no active ingredient; worse yet, some contained toxic substances.
One estimate by experts is that at least 100,000 people die every year from substandard and fake medicines for cancer, heart disease, infectious diseases and other ailments. Fake malaria drugs pose a real risk of hampering the international effort to curb the disease. In wealthy nations, substandard or fraudulent drugs have caused thousands of adverse reactions and some deaths.
The United States, despite having a strong regulatory agency, is hardly immune to this problem. In recent years, fake doses of Avastin sold to physician groups for cancer treatment lacked the active ingredient; a weight-loss medicine contained undeclared ingredients that posed a health risk; and compounding pharmacies have produced contaminated drugs that caused meningitis and deaths.
An analysis by health experts published in the British Medical Journal last week lamented the lack of progress in addressing this scourge. The group called for a global treaty backed by governments, drug companies and nongovernmental groups to ensure a safe drug supply.
Crackdowns by international police and national regulatory agencies have made progress in shutting down dangerous online pharmacies. But, in poor countries, the greater problem is keeping bad products out of the supply chain that serves pharmacies and health care provider groups. In Kenya, even Doctors Without Borders, a smart operation, was duped into buying fake antiretroviral drugs to combat AIDS, which it gave to thousands of patients before the fraud was discovered.
There is an urgent need for a more vigorous international effort. That might include stronger surveillance and research to determine the extent of the problem, clearer definitions for bad drugs (substandard, counterfeit, falsely labeled, falsified or fraudulent drugs, for example) and new international laws to make it a crime to traffic in such medicines.HHS has issues a proposed rule that would increase the number of drugs eligible for reimbursement by insurers under the Affordable Care Act's essential health benefits requirements. In a previous bulletin, HHS said it planned to require that essential health benefits cover only one drug in each therapeutic class included in benchmark plans put forward by each state. The new rule essentially changes the language from 'only one' to 'at least one' drug, requiring that insurers cover at least one drug per therapeutic area or the same number of drugs in each category and class as specified in the state benchmark plan, whichever is greater.
BioCentury reports that the proposed rule also states that a plan "must have procedures in place that allow an enrollee to request clinically appropriate drugs not covered by the health plan." Comments on the proposed rule are due Dec. 26. Previous comments on HHS' bulletin said a one-drug requirement would have provided insufficient access to medications for some conditions. Medicare Part D requires that drug plans provide access to "all or substantially all" medications in six therapeutic classes.
HHS also released a proposed rule that prohibits health insurance companies from discriminating because of a preexisting or chronic condition, as well as a proposed rule on implementing and expanding employment-based wellness programs.
When it comes to jurisdiction over compounding pharmacies, Senator Lamar Alexander (R, TN), wants someone “on the flag pole” responsible for ensuring that non-traditional compounders meet set federal standards.
Alexander proposed allowing FDA to designate state boards of pharmacy as the primary regulator, if they are willing and able. If the state regulators proved unable or made mistakes, FDA would have the ability to take over regulation.
FDA Commissioner Hamburg gave that idea a positive nod, saying it was one model that could be explored, but she still wants federal regulations to assure consistency.
“I think it should be made explicit,” she said. “I think for non-traditional compounding there should be federal standards that apply to certain types of practices that go to issues of quality and safety.”
FDA said those facilities should be required to submit to inspections, report adverse events and register with the agency.
On the House side, Tom Harkin (D, IA), suggested that compounding facilities shipping across state lines should come under FDA scrutiny. Other ideas included using a volume threshold and prescription records.
If the FDA gets more responsibility – which is looking increasingly likely -- they will also need more funding. Otherwise this is all just C-SPAN rhetoric.
Did somebody say “sequestration?”
The election may be over, but the malarkey continues.
The most recent Marlarkey Alert comes to us courtesy of the New York Times editorial page.
In defense of the IPAB, the Gray Lady editorializes:
The board, known as the Independent Payment Advisory Board, has been the subject of false attacks over the past few years by Republicans who claim that it will ration care, disrupt doctor-patient relationships, and tell patients what treatments they can receive. That is an outlandish way to describe a board that is prohibited by law from making any recommendations to ration care, raise premiums, increase cost-sharing, restrict benefits or limit eligibility.
That’s malarkey.
Medicare spending is expected to be $575.7 billion this year, jumping to over $1 trillion by 2022, as the country ages. Over the next 75 years, the program is projected to accumulate a $38 trillion budget shortfall.
Much of this enormous price tag goes towards financing Medicare Parts A (hospital insurance) and B (medical services -- including diagnostic tests and doctor visits). And yet, IPAB has no authority over either. And the board can’t make any substantive structural changes. Neither the fee-for-service structure nor enrollee premiums and fees can be altered.
The board’s only viable option is to further ratchet down reimbursement rates for Medicare providers, especially doctors, who are already losing money on Medicare patients. Indeed, the financial burden of too-low payments under Medicare has driven 17 percent of doctors and 31 percent of primary care physicians across the country out of the Medicare program altogether, according to a study from the American Medical Association.
If rates fall any lower, seniors will have an increasingly difficult time securing doctor appointments. Visits will be cut short to squeeze in patients and care compromised.
Lawmakers must cast aside IPAB’s flawed approach (and the media malarkey surrounding it) and focus instead on innovative initiatives that address the program’s real cost-drivers while protecting seniors’ access to care.
There is no greater disaster than greed.
– Lao-tzu
The tragic deaths caused by the current drug compounding scandal could so easily have been avoided. The root cause wasn’t a drug shortage – it was greed.
A new effort by Representatives Ed Markey (D, MA), Henry Waxman (D, CA), John Dingell (D, MI), Frank Pallone, Jr. (D, NJ), Diana DeGette (D, CO), and Anna Eschoo (D, CA) is aimed at getting to the bottom of the problem by investigating the roles of the players in this horrible drama – specifically the actions of Group Purchasing Organizations (GPOs).
Mr. Markey: “As Congress fully investigates all the causes of the tragic meningitis outbreak in an effort to protect patients in the future, we need to look at the role GPOs play in the occurrence of drug shortages that could lead to increased reliance on compounding pharmacies.”
“Through our investigation into drug shortages and the meningitis outbreak, we have discovered that medical professionals have increasingly been turning to compounding pharmacies for their prescription needs,” said Mr. Dingell. “It is important we study every potential cause of this outbreak in order to get to the bottom of this health crisis. I look forward to working with my colleagues in the coming weeks to explore legislative approaches that will address this matter.”
Representative DeGette: “While we've begun to address drug shortages legislatively, it is clear we must aggressively investigate the factors that led to this deadly outbreak and determine possible remedies, so we can take steps to save patients lives.”
“If group purchasing organizations are taking advantage of their unique role in facilitating a safe and reliable drug supply, then we need to know about it,” said Representative Eshoo.
Mr. Waxman, “In light of the tragedy of the meningitis outbreak linked to contaminated compounded drugs, we need to look carefully at all factors that might be contributing to the increasing use of compounded drugs by hospitals and other health care providers.”
“This initiative is a courageous step forward in addressing the foundational reasons behind both the tragedies caused by drug compounding and the broader issue of preventable drug shortages,” said Peter J. Pitts, President, Center for Medicine in the Public Interest and a former FDA Associate Commissioner. “The anticompetitive manipulation of American healthcare by GPOs is an urgent topic for congressional action.”
The full Congressional release can be found here.
BioCentury reports:
FDA issues first breakthrough designation
FDA has "recently" issued the first breakthrough drug designation, Janet Woodcock, director of the Center for Drug Evaluation and Research, said on Wednesday. She said the agency cannot disclose the sponsor or drug candidate. The breakthrough designation, created by the FDA Safety and Innovation Act, commits FDA to collaborate with a sponsor to accelerate product testing and development.
"Drug manufacturing could be the rate limiting step" for implementing the breakthrough drug pathway, Woodcock said at a meeting sponsored by Friends of Cancer Research and the Brookings Institution's Engelberg Center for Health Care Reform. FDA will work with sponsors to improve the chances that manufacturing is scaled-up and approved at the time when breakthrough drugs are approved, she added.
Mirror, mirror on the wall – whose delaying innovation most of all?
Should the new third leg of the FDA review process be … investment considerations?
Jonathan Leff, managing director of Warburg Pincus LLC, believes that the FDA should consider the cost of drug development when making its regulatory decisions.
At a conference on rare diseases conference sponsored by the Drug Information Association and National Organization for Rare Disorders, Leff said FDA should think about the effects of its demands on sponsors, such as the additional cost another efficacy trial would create should the agency demand it.
That’s a bad idea. While there are many things the FDA can and should do that would result in lower drug development costs – the issue has no place in the regulatory review process. It is as inappropriate a third leg as comparative effectiveness. The regulatory process must rest on the twin pillars of safety and efficacy.
Leff does not agree. “We must recognize that if a system is set up to ensure safety and efficacy and no mechanisms are designed into it to take the economic burden into account, we should expect to see as an unintended consequence, exactly what we have seen, which is relentlessly increasing time and cost.”
"Because of that time and cost, venture investors and pharma companies are now unable to make new investments to initiate development of many promising new therapies and as a result the next generation of potential breakthrough treatments … may never have a chance.”
Indeed, we are seeing an increase in time and cost – and these are serious roadblocks to continued investment in innovation. But whether this is entirely the fault of the FDA is not as simple as Leff makes it seem. He’s parroting the party line of those who choose to blame their developmental failures on the FDA. There is a medical device to address this myopia – it’s called a mirror.
Mr. Leff is only repeating the broader opinion of the investor community. The National Venture Capital Association's (NVCA) Medical Innovation & Competitiveness Coalition found that 39% of firms reduced investment in life sciences companies over the last three years. The same percentage expects to further decrease investment over the next three years. The venture capitalists surveyed largely blamed the Food and Drug Administration's restrictions and regulatory challenges for this trend.
Pharmaceutical companies must evaluate their level of responsibility for shrinking investment expenditures. If they want venture capitalists to continue investing in medical research and development, they must produce high-quality drugs worthy of FDA approval – and stop whining when their “miracle drugs” require more clinical evidence.
The solution isn’t for the FDA to weigh the financial investments of biopharmaceutical companies in its regulatory decision process. The solution is to make the regulatory process more predictable.
A quarter-century ago, the success rate for a new drug used was about 14 percent. Today, a new medicinal compound entering Phase 1 testing — often after more than a decade of preclinical screening and evaluation — is estimated to have only an 8 percent chance of reaching the market. For very innovative and unproven technologies, the probability of a product’s ability to make it to the market is even lower. We must work together to turn that around.
When Thomas Edison was asked why he was so successful, he responded, “Because I fail so much faster than everyone else.” Consider the implications if the FDA could help companies fail faster. Using the lower end of the Tufts University estimate of the average pre-tax cost of new drug development, $802 million:
- A 10 percent improvement in predicting failure before clinical trials could save $100 million in development costs.
- Shifting 5 percent of clinical failures to Phase 1, the earliest stage, from Phase 3, the latest stage, reduces out of pocket costs for developers by $15-$20 million.
- Shifting of failures to Phase 1 from Phase 2, the middle stage, would reduce their out of pocket costs by $12-$21 million.
All of these dollars could then be reinvested in other innovative development programs for new life-saving medicines.
For all that modern science has to offer, developing new treatments is still very much an art, in which hunches, intuition, and luck play a critical role. The odds are long. But for more medicine that is affordable and innovative, we need up-to-date regulations that compliment the drug trial process in order to take these chances, which is precisely the mission of the FDA’s Reagan-Udall Foundation.
“I’ll tell you as a venture capitalist, I have been forced to not make investments in rare disease opportunities that we might have or almost certainly would have invested in 10 years ago because of a perception that if we do a clinical trial, and given all the unknowns in this area, miss slightly on the statistical goals, that would be game over for that development program,” he said during the conference.
That may be so. But drug reviews are not and should not be predicated on the calculations of venture capitalists.
But that doesn’t mean maintaining the status quo is acceptable.
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.
