Mutual of Pretoria

08/14/2013 06:59 AM |

South Africa seeking mutual recognition with FDA and EMA.

Maybe a better first step is to establish a reference basket of maybe five to six countries. A good model is Singapore. Everyone’s favorite city-state reviews six countries—USA, Canada, Australia, NZ, Japan, Switzerland and the EMA.  If any two of the five have approved, then approval is basically a formality.

Singapore doesn’t have mutual recognition with either the FDA or the EMA, but they unilaterally recognize the benefits of referencing to the “big regulatory dogs”, but did not demand that the FDA reference to their tiny agency.

 New medicine control body a step closer
Tamar Kahn: Business Day

THE establishment of a new regulatory body for medicines is a step closer, after the Cabinet said yesterday that it had referred enabling legislation containing the Medicines and Related Substances Amendment Bill to Parliament.

The bill will replace the Medicines Control Council (MCC) with the South African Health Products Regulatory Agency (Sahpra), an entity with much wider scope.

The Cabinet said the bill sought to establish a strong, efficient and effective medicine regulatory authority. The Department of Health envisages Sahpra as being the solution to the extensive delays besetting the MCC, which takes much longer compared with US or European regulators to approve new medicines and clinical trials.

It is also expected to bring scrutiny to bear on aspects of the market that have largely gone unregulated, such as medical devices and complementary medicines. The new regulatory agency will also be responsible for foodstuffs, cosmetics, disinfectants and diagnostics.

To the frustration of researchers and the pharmaceutical industry, Sahpra has been stuck in the works for years. In 2008, Parliament passed amendments to the Medicines and Related Substances Act, which were not implemented. The bill was subsequently redrafted and published for comment in March. Since then it has taken more than a year to refine the bill and get it through the Cabinet.

Department of Health director-general Precious Matsoso said in June that one of the key changes made to the draft legislation was the inclusion of provisions for Sahpra to be a public entity with an independent board chaired by a CEO. It would also have a stronger governance structure than the previous draft, which had a CEO appointed by the Health Minister and gave final authority for the approval of new products to the Minister. The draft bill also included measures to shorten the registration time for medicines and medical devices by allowing mutual recognition agreements between Sahpra and other regulatory authorities such as the US Food and Drug Administration.

  Read More & Comment...

Interface Race

08/13/2013 08:41 AM |

From the pages of Health Affairs:

Electronic Communication Improves Access, But Barriers To Its Widespread Adoption Remain

Abstract

Because electronic communication is quick, convenient, and inexpensive for most patients, care that is truly patient centered should promote the use of such communication between patients and providers, even using it as a substitute for office visits when clinically appropriate. Despite the potential benefits of electronic communication, fewer than 7 percent of providers used it in 2008. To learn from the experiences of providers that have widely incorporated electronic communication into patient care, we interviewed leaders of twenty-one medical groups that use it extensively with patients. We also interviewed staff in six of those groups. Electronic communication was widely perceived to be a safe, effective, and efficient means of communication that improves patient satisfaction and saves patients time but that increases the volume of physician work unless office visits are reduced. Practice redesign and new payment methods are likely necessary for electronic communication to be more widely used in patient care.

1. Tara F. Bishop1,*,
2. Matthew J. Press2,
3. Jayme L. Mendelsohn3 and
4. Lawrence P. Casalino4

1. ¹Tara F. Bishop (tlfernan@med.cornell.edu) is an assistant professor in the Departments of Public Health and Medicine at Weill Cornell Medical College, in New York City.
2. ²Matthew J. Press is an assistant professor in the Departments of Public Health and Medicine at Weill Cornell Medical College.
3. ³Jayme L. Mendelsohn is a research coordinator in the Department of Public Health at Weill Cornell Medical College.
4. ⁴Lawrence P. Casalino is the Livingston Farrand Associate Professor in the Department of Public Health at Weill Cornell Medical College.

1. ↵*Corresponding author

  Read More & Comment...

"D" is for Dual Eligibility

08/12/2013 08:15 AM |

From the pages of the South Florida Sun Sentinel …

Competition from insurers is benefit for consumers

How do you know a federal government program is working? When states start using it as a model for their own initiatives. That's what's happening with Medicare Part D, the prescription drug program for seniors. States are incorporating its unique market-based structure into their own healthcare programs to expand access and manage costs.

Under Medicare Part D, seniors select their prescription coverage from a host of private insurers. States are now applying that principle of free market competition to their Medicaid programs, and the results have been excellent.

Kansas, Louisiana, and Florida have received federal waivers that allow them to experiment with providing Medicaid services through private insurers. The states pay a fixed amount to insure each Medicaid enrollee, and then set minimum benefits that plans must provide.

But it's private insurers that actually supply the plans, and it's the enrollees themselves who decide which plan they would like. As a result, insurers can't provide the bare minimum — Medicaid enrollees can easily select a more appealing plan based on their own needs.

The results have been impressive. When Florida recently ran a pilot program, participating counties outperformed others 64 percent of the time on measured health outcomes. In Louisiana, where those on private insurance have the option of returning to the state's traditional Medicaid program, only one-third of 1 percent have chosen to do so. And because these states expect to save money, other states, including North Carolina, Texas, and Utah, are now considering similar policies.

And these programs don't just promise to save money, they feature various innovations to ensure quality. For example, in Florida, insurers are required to conduct customer-satisfaction surveys. While some states have increased the amount they will pay for coverage of high-risk patients, giving insurance companies an incentive to cover these patients and keep them healthy. This type of risk-based pricing helps patients receive more preventive care, according to a report last year by the Urban Institute.

Nationwide, 36 states and the District of Columbia provide at least some of their Medicaid services through private insurers — and these programs are expected to grow as the new health-care law expands access to Medicaid. States already spend up to one-third of their budgets on Medicaid, so an opportunity to save money while providing better service is an obvious win.

All of this is exciting — but it's not surprising, at least not to those who are familiar with the success of Medicare Part D. By letting seniors choose between private drug plans, Part D has cost the government about 45 percent less than initially projected when Congress enacted the program in 2003.

Out-of-pocket expenses for seniors are also lower than expected. And in a recent survey, 90 percent of Part D beneficiaries said they were satisfied with the program.

Given Medicare Part D's success in its own right and as a model for other healthcare programs, it's bizarre that the president and some in Congress would like to undermine the competition that makes Part D work.

The president's most recent budget, as well as bills introduced in Congress by Sen. Jay Rockefeller and Rep. Henry Waxman, would require drug companies to give "rebates" to the government for the drugs purchased for low-income seniors — known in technical parlance as "dual eligibles" because they qualify for both Medicare and Medicaid.

To put it simply, these politicians would substitute government price controls for the competitive marketplace that has been so effective in keeping costs down. As the Congressional Budget Office has reported, the private plans provided through Part D are already negotiating low prices for drugs. Requiring drug makers to, instead, sell their products for below-market prices will force manufacturers to raise prices on other consumers, including most seniors. Such rebates could increase seniors' premiums by 40 percent, according to a study by former CBO director Douglas Holtz-Eakin.

States may be the laboratories for innovation, but the big lesson from Part D is clear: Competition between private insurers reduces costs and encourages better health care. Some states are learning this lesson and applying it to their Medicaid programs. The federal government should be encouraging this market-based reform, not trying to undermine it.

Peter J. Pitts, a former FDA Associate Commissioner, is President of the Center for Medicine in the Public Interest.

  Read More & Comment...

Oregon Trail?

08/09/2013 07:11 AM |

From the pages of the Wall Street Journal.  Frightening.

Rationing Health Care in Oregon

BY: HOPE LANDSEM

Liberal states often preview health-care central planning before the same regulations go national, which ought to make an Oregon cost-control commission especially scary. On Thursday a state board could change Oregon's Medicaid program to deny costly care to poor patients who need it most.

Like most such panels, including the Affordable Care Act's Independent Payment Advisory Board, the Oregon Health Evidence Review Commission, or HERC, claims to be merely concerned with what supposedly works and what doesn't. Their real targets are usually advanced, costly treatments. That's why HERC, for example, proposed in May that Medicaid should not cover "treatment with intent to prolong survival" for cancer patients who likely have fewer than two years left to live. HERC presents an example to show their reasoning for such a decision: "In no instance can it be justified to spend $100,000 in public resources to increase an individual's expected survival by three months when hundreds of thousands of Oregonians are without any form of health insurance."

Amazingly enough, the Affordable Care Act quashed that one. The law says coverage decisions cannot discriminate against people because of their diagnoses and life expectancies.

So HERC changed a few words of its proposal. Before, the plan would have limited treatment based on life expectancy. Now, the plan will determine whether an individual continues to receive potentially life-saving treatment based on the severity of the illness, using ambiguous performance statuses, a scale that tries to quantify a cancer patient's well-being. Some difference.

This is a recurring theme in HERC's Medicaid overhaul. The commission also suggested guidelines that would limit to once a week the number of times some diabetics could check their blood sugar, down from the three tests a day the American Diabetes Association recommends now. Outrage from diabetics, not to mention medical experts, forced the commission to postpone that vote.

The public isn't receiving the cancer proposal any better. In a letter to HERC, a Willamette Valley Cancer Institute and Research Center patient navigator, a trained health-care worker responsible for educating cancer patients and guiding them through various treatment options, writes that "patients deserve treatment that is available based on the best evidence, not on a timeline." We'll learn today if HERC is willing to restrict potentially life-saving treatment in favor of the left's one-size-fits-all health approach.

  Read More & Comment...

CMPI Event: “Personalized Medicine and Responsible Access to Pain Medication.”

08/07/2013 02:56 AM |

Please join the Center for Medicine in the Public Interest (www.cmpi.org) and some of the nation’s top experts for an interactive panel discussion of “Personalized Medicine and Responsible Access to Pain Medication.”

A Capitol Hill Briefing

When: September 10, 2013 from 9:30AM – 2:15PM

Where: Rayburn House Office Building B338, Washington DC

RSVP: Mario Coluccio at mcoluccio@cmpi.org

BREAKFAST & LUNCH TO BE SERVED

AGENDA

9:30- 10AM:  Breakfast and Registration

10AM: Welcome
            Peter Pitts & Robert Goldberg, Center for Medicine in the Public Interest

10:15: Keynote: FDA Regulation and Responsible Access to Pain Medication
            Douglas Throckmorton, Deputy Director, Regulatory Programs, CDER, FDA

11:00: Access to Pain Medications: The Role of Patients and Manufacturers
            Moderator: Steve Usdin, BioCentury
            Cindy Steinberg, US Pain Foundation
            Bob Twillman, American Academy of Pain Management
            Stuart Kim, Mallinckrodt Pharmaceuticals

11:45: Break and Lunch

12:00: Issue:  Pain Medications:  Two Reporters Views
            Moderator: Peter Pitts, CMPI
            Barry Meier, New York Times
            Judy Foreman, Syndicated Columnist

1:30:  Closing Keynote: Pain Medications and the Future of Personalized Medicine
            Introduction: Bob Goldberg, CMPI
            Charles Inturrisi, Weill Cornell Medical Center
 
2:15: Closing Remarks
 
Peter Pitts & Robert Goldberg, Center for Medicine in the Public Interest
 
RSVP: Mario Coluccio at mcoluccio@cmpi.org

BREAKFAST & LUNCH TO BE SERVED
 

  Read More & Comment...

B Cause

08/06/2013 07:36 AM |

From the pages of Forbes.com.

Medicare Budget Cuts Could Threaten Cancer Patients' Access To Drug Treatments

By Peter J. Pitts

Earlier this month, Forbes guest commentator John Wilson celebrated cuts planned for Medicare Part B as a result of sequestration and called for additional “savings” to be wrung out of the program.

Across-the-board federal budget trimming has forced the Centers for Medicare and Medicaid Services (CMS) to significantly reduce the reimbursement rate for healthcare providers that participate in Part B, which covers drugs that have to be administered under professional supervision.

Mr. Wilson thinks these rate cuts are a good start — and he wants more. He claims that “Part B drugs have a history of CMS overpayments” and suggests additional reimbursement reductions won’t have any ill effects.

He’s mistaken.

The model for Part B provider payments is working well to bring down long-term healthcare costs and ensure enrollees have access to needed medication. Additional reimbursement reductions will compromise care in communities throughout the country while doing little to curtail Medicare expenses.

Under Part B, doctors pay for medications on their own and are then reimbursed according to a formula: the average market price for that drug plus an add-on to cover administrative expenses. That additional compensation above the prevailing price is crucial. It helps participating healthcare providers finance other crucial, resource-intensive aspects of treatment, like drug acquisition and storage.

Under this unique, market-like setup, caregivers have an incentive to find the best treatment for the lowest price. Indeed, the Congressional Budget Office projected that this reimbursement system would generate $16 billion in savings over its first decade of operation. And yearly cost growth for the program has been below overall medical inflation.

One major study found that Part B’s reimbursement formula reduced drug spending by over seven percent during the program’s first year of operations. And it limited Part B’s average annual expense growth rate to just 2.4 percent, compared to nearly 11 percent for all of Medicare.

Community health clinics are major participants in Part B. These locally oriented operations tend to be significantly more cost-efficient than larger hospitals. By properly compensating clinics and encouraging them to treat Medicare enrollees, Part B saves the government money over the long-run. For instance, research from the consulting group Milliman has found that Medicare saves an average of $6,500 per year when a patient receives chemotherapy treatment at a clinic rather than a hospital.

All in all, Part B’s reimbursement formula has been working terrifically well. But as a result of sequestration, CMS will be cutting that administrative add-on by about two percentage points — from six to four percent. And some in Washington are looking to ratchet back this reimbursement even further, to closer to three percent.

Further cutting this rate would seriously threatens the financial viability of many of the community health clinics currently participating in Part B. These operations already run on exceedingly thin profit margins. They depend on proper compensation from Part B and other public programs to stay afloat. Reducing reimbursements would force many clinics to close and physicians to turn away enrollees.

New cuts would make a bad situation even worse, particularly in the realm of cancer treatment. According to the Community Oncology Alliance, over the last six years, 288 cancer clinics have closed. Another 469 have entered into a contractual relationship with a hospital or been acquired by a hospital. And 407 report they’re struggling financially.

The American Society of Clinical Oncology predicts that Part B cuts could force up to three-quarters of the remaining cancer clinics in the country to start redirecting Medicare patients to other caregivers.

Mr. Wilson also argues for scaling back the intellectual property protections currently afforded an advanced class of pharmaceutical drugs called biologics. These are highly complex treatments derived from living organisms. In addition to standard patent controls, biologics are also provided 12 years worth of data protection preventing generic competitors from accessing the original innovators research information.

The provision establishing these 12 years of data protection was included in the President’s 2010 health care reform law — and it was one of the few provisions that enjoyed broad bipartisan support from both chambers of Congress.

After noting that 12 years is “far longer than for most other drugs,” Mr. Wilson joins the chorus of misinformed critics calling for biologic data exclusivity to be scaled back to seven years. He thinks such a move would save the public health system billions in drug expenses by expanding the pool of low-cost generic alternatives.

But that 12 year set point isn’t arbitrary. Virtually all the research on this subject shows that that’s about as long as it takes for the average biologic to break even in sales. The average new drug costs on average $1.2 billion to research, develop and bring to market. And just two out of every ten new drugs ever turns a profit.

Cutting down the period of data protection to just seven years would flood the biologic market with generic competition well before most innovators have had time to get out of the red. Drug developers would be much less likely to invest in new products in the future and patients would be deprived of new breakthrough treatments.

Mr. Wilson and I are in agreement that public officials need to find effective ways of controlling Medicare costs without compromising enrollee care. But further cutting Part B reimbursements and reducing the protection of intellectual property for innovative drug companies doesn’t fit the bill — it will undermine community caregivers and choke off patient access to needed medicines.

Peter J. Pitts, a former FDA Associate Commissioner for External Affairs, is President of the Center for Medicine in the Public Interest.

  Read More & Comment...

How We Can Cure Cancer Sooner

08/05/2013 01:04 PM |

Tailoring cancer studies to fit people who need to get better 

Imagine if our immune systems could vanquish cancer in much the same way they take on the common cold. New research could turn such science fiction into fact.

Currently in the works are several new drugs that can order certain white blood cells - the immune system's warriors - to attack cancer cells. If they prove successful, a world free from cancer could be one step closer. Researchers are increasingly exploring how we can personalize the fight against cancer - harnessing the unique characteristics of our own bodies to beat the disease. Such personalized approaches offer our best shot at eradicating cancer - and should be at the heart of our battle plan against it. Medical science has already made progress.

Since 1990, new medicines have doubled the number of cancer survivors - from six million to 13 million. They have given patients collectively about 43 million years of additional life. These aren't years of pain and desperation. Cancer survivors add about $4.7 trillion in value to the economy just by living and working longer. Today, every dollar spent on new cancer medicines reduces spending on hospitals and doctors by $7. Yet the actual amount we spend on such treatments is small - about 1 percent of total health-care spending. Indeed, spending on innovative cancer research and therapies has already delivered a hefty return on investment. We should double down on that approach.

Step one is to put patients in charge of cancer research. How? Patients can use online communities to test treatments, design studies, and determine better ways to tackle their illnesses. They're already keeping tabs on their health with fitness monitors and tablets. Research should be shaped by these real-time, real-world experiences in combination with information about the particular genetic mechanisms that make their tumors tick. As genomics professor Eric Topol argues: "It is time for a jailbreak; it is time for the rise of the consumers to drive the future of medicine. It is their DNA, their medical data, their cellphones, and their own health at stake."

That jailbreak should include replacing one-size-fits-all research with personalized cancer studies. The Human Genome Project empowers researchers to do so. Personal genomes can now be sequenced in a few hours for under $500. Such sequencing can yield medicines that are truly personalized. Several cancer organizations, including the International Myeloma Foundation, StandUp2Cancer, and the Sarcoma Foundation of America, require researchers to look for genetic cues that could lead to cures. This should be the rule, not the exception.

These personalized approaches could also allow regulators to get new cancer medicines to market faster. Developing a new cancer medicine takes 8.8 years, on average - much longer than for other drugs. Most of this time and effort is spent testing medicines in people who researchers know won't benefit. But by focusing solely on patients and their specific cancer-causing genetic mutations, researchers could identify what therapies work early on. That could mean approving cancer therapies as fast as HIV medicines - in two to three years.

Government officials can also get personalized treatments into the hands of patients more quickly by requiring health plans to pay for them. Advances in cancer treatment are saving lives and cutting health-care costs. But many health-insurance plans haven't caught up with the times. Many cancer patients are forced to choose between a treatment that could save their lives - or one that's paid for. Insurers should instead pay for the right treatment for the right patient.

Under the health-care status quo, cancer treatment is divided up according to who gets paid. Innovations that save money are pitted against services that lose money. New "Charter Cancer Communities" can solve that problem by focusing specifically on the value of care. Like public charter schools, these communities would have greater flexibility to use and pay for the combination of treatments that deliver real value. And they'd be accountable to the member organizations and to the patients they serve. Thanks to recent advances in medical science, we're closer to a world free from cancer. If we ratchet up our investments in personalized medicine, that world can become a reality.


  Read More & Comment...

A Limited Use Consensus -- in more ways than one

08/05/2013 07:25 AM |

On Thursday I joined a select group of FDA and healthcare policy experts at the joint FDA/Engelberg Center for Health Care Reform (Brookings Institution) to discuss, debate, and digest the many issues surrounding the thorny opportunity known as Special Medical Use (SMU).

Expertly chaired by Mark McClellan (my former boss at the FDA and the hardest working man in healthcare policy), the day was filled with honesty, ideas, identification of roadblocks – and frustration.

But all to the good.

The meeting was also filled with many senior thinkers and heavy hitters from the agency (Rachel Sherman, John Jenkins/OND, Janet Woodcock, among others) as well as senior Hill staffers, officials from the biopharmaceutical industry, BIO, PhRMA, payers, patient organizations, and academia. The list of attendees can be found here.

First of all, permit me to recommend the short briefing paper that McClellan’s team developed in advance of the meeting, “Special Medical Use: Limited Use for Drugs Developed in an Expedited Manner to Meet an Unmet Medical Need.” Worthwhile reading both as a primer and a guide to many of the regulatory quandaries surrounding SMU.

The meeting began with McClellan commenting that we needed to “channel PCAST” and making the key distinction (regularly confused) that the difference between special medical use (from a labeling perspective) and REMS – is that REMS is for known safety risks.

And then came Janet.

Her remarks focused understanding SMU along the “safety and certainty” continuum.  SMU medicines are for sub-segments of a patient population (with a serious and life-threatening disease) that are not effectively served by current therapies. “There’s a difference between headaches and HIV.” And that wasn’t a throwaway line. In fact, there was zero mention or acknowledgement that SMU should be a pathway exclusively for anti-infectives. Janet strongly affirmed that the FDA has no interest in interfering in the practice of medicine. To the contrary, she believes the best way to ensure that SMU products are used appropriately is through clear and distinct labeling – special logo, etc.

This makes perfect sense and is a logical extension of the agency’s Safe Use of Drugs initiative.

Janet also raised the issues of SMU products and industry promotional practices. Her feeling is that (as with other Breakthrough Designation programs) that pre-view of all marketing materials would be an SMU prerequisite. She also raised the interesting question of seeking to limit on-label communications in order to drive “appropriate messaging from launch because appropriate messaging leads to appropriate use.”

Tom Abrams, call your office.

Janet also noted the fear of many in industry that the FDA would “deem” an SMU designation. She made it clear that would not be the case.

After Dr. Woodcock’s opening keynote, the first panel of the event focused on “The Special Medical Use Pathway Proposal.” The panelists were Jim Greenwood (BIO), John Castellani (PhRMA), Jack Lasersohn (The Vertical Group), Margaret Anderson (FasterCures), and Jeff Allen (Friends of Cancer Research).

And, while there were no fireworks – there was a degree of discomfort – specifically on SMU and legislation, regulatory authority, and therapeutic areas of use.

Here’s how Steve Usdin at BioCentury saw it:

BIO, PhRMA split on special use pathway

The leaders of the Biotechnology Industry Organization and the Pharmaceutical Research and Manufacturers of America staked out separate positions on the creation of a Special Medical Use pathway proposed by the President's Council of Advisors on Science and Technology and senior FDA officials …

BIO President and CEO James Greenwood said the group's board "strongly approves" of SMU, endorses congressional action to create the pathway and feels it should be "broadly applied" to drugs for a wide range of diseases. John Castellani, PhRMA's president and CEO, declined to endorse creation of an SMU pathway and said FDA has sufficient authority to approve drugs for special populations, though he stressed the urgency of facilitating development of new anti-infective drugs. Members of Congress have indicated that enactment of legislation creating an SMU pathway is contingent on unanimous support from industry, so PhRMA's skepticism about the need for an SMU pathway could scuttle the concept.  

While the general sense of Usdin’s comments is correct, it may not be quite so black and white.

Both Greenwood and Castellani support the concept of SMU. And that’s an important point of departure. Greenwood, while supporting the concept of legislation, believes that the FDA already has the regulatory authority to create a Special Medical Use pathway and the ensuing labeling for such products. He said that, rather than pushing for actual legislation, that a “sense of Congress” might be a better idea.

Dr. Woodcock, call your lawyers.

Castellani agreed that the agency already as the authority to move forward. So there’s important convergence there. But he was less clear on the issue of an SMU pathway that went beyond anti-infectives. I specifically asked him if he felt the SMU pathway should be limited to anti-infectives. His answer was to reiterate PhRMA’s concerns about “direct or indirect” impact on the practice of medicine and possible agency hindrance of appropriate promotional communication.

Both Margaret Anderson and Jeff Allen feel that the SMU pathway should be open to any appropriate therapeutic area. Jeff Allen made a key point, that the SMU pathway is possible because of advances in science. It sounds like a simple point – and it is – but it’s important to recognize that SMU is the next logical step towards personalized medicine.

Margaret Anderson also got real by pointing out that, minus additional budget, the FDA will only be able to go so far. “How much innovation,” she asked, “can the agency be expected to handle?”

Indeed.

The general consensus was that SMU should be piloted with anti-infectives – but proceed rapidly to where the need is the greatest. Bravo – but highly subjective.

John Castellani, call your office.

Panel Two operated under the moniker, “Implementation and Impact of Special Medical use Products in Clinical Practice” – but this was really the payer panel.

Sam Nussbaum (WellPoint) brought the urgent issue of patient outcomes into the conversation. His point was (per reimbursement) that if the SMU process works as designed (limited use with an enhanced risk/benefit profile in a defined sub-population) that they would be swiftly tiered for reimbursement.

Pursing the topic of the role payers have in outcomes, Ed Septimus (HCA Healthcare) stated that, “Stewardship is resource intensive.” True – but lack of stewardship is even more costly in terms of scarce dollars and clinical sense – and patient lives.  Septimus also introduced the concept of mandatory patient registries.

I asked the panel if, as part of the regulatory process, the FDA should mandate patient registries for SMU medicines. There was an uncomfortable silence.

Gerald del Pan, call your office.

Panel III: “Postmarket Considerations to Promote Safe Use and Continued Evidence Development of Special Medical Use Products” opened with Preeti Pinto (former AZ compliance chief and now consultant extraordinaire to the regulatory stars) stating that, “Marketers will promote the product to the full extent of the label.” No surprise there, but a real issue when it comes to promoting safe use of SMU medicines. Can marketers self-regulate? Is that even feasible? Short of an OPDP SWAT team for SMU medicines (with the authority to apply harsh penalties) how can marketers (per Preeti’s prescience) be made to “do the right thing?” What are the appropriate tools for post-marketing surveillance and how can they be validated?

Rob Califf (Duke Translational Medical Institute and Duke University Medical Center) pointed out that the label has become nothing more than a tool for legal protection – dismissing any future utility. But, in a post Wyeth v. Levine world, with preemption off the table, perhaps now is precisely the right time to revisit the public health utility of the PI.

Perhaps, as part of the SMU pathway, the FDA should adopt the EPARS (European Public Assessment Reports) system. The European Medicines Agency (EMA) publishes an EPAR for every medicine granted a central marketing authorization by the European Commission. EPARs are full scientific assessment reports of medicines authorized at a European Union level. 

Rachel Sherman, call your office.

An “almost” consensus of the meeting was the SMU pathway should proceed apace with anti-infectives as the pilot program and under existing regulatory authority. Almost. Maybe.

  Read More & Comment...

Special Medical Use: Take One

08/02/2013 07:23 AM |

Yesterday I participated in the Brookings Institution/FDA meeting on Special Medical Use. I am gathering my notes and will have a more complete report ready for Monday.

In the meantime, here is an interesting take on the issue from the pages of Specialty Pharmacy Times.

FDA’s New Expedited Approval Program Provides Major Communication Breakthrough for Industry

Drugs that show a clear or substantial benefit to patients in the earliest stages of clinical trials can now reach the market more quickly, thanks to the FDA’s new Breakthrough Therapy designation. The expedited pathway, introduced by the Food and Drug Administration Safety and Innovation Act of 2012, has the potential to shave off nearly 75% (or by some accounts, nearly 2 years) of the time it typically takes the FDA to review a new drug application.

One of the major innovations of the expedited drug development process appears to be that drug companies now have direct access to something that previously eluded them: FDA officials. According to Reuters, efforts to bring promising therapies to market have been well-coordinated through the use of these pathways, and communications “that might typically take weeks and months” have been occurring more quickly, with fewer gaps between interactions.

The FDA began granting breakthrough designations in January 2013. To date, the agency has received 77 requests. Of these, the regulatory body has granted 25 designations and denied 24. Kalydeco (ivacaftor), Vertex’s cystic fibrosis drug, was approved under the breakthrough designation pathway earlier this year. Anticipated blockbusters such as Genentech’s obinutuzumab and Janssen/Pharmacyclics’ ibrutinib have snagged breakthrough designations as well. Obinutuzumab was granted the designation for the treatment of chronic lymphocytic leukemia (CLL), and ibrutinib was granted 2 breakthrough designations: one to treat patients with CLL and the other for patients with mantle cell lymphoma.

Although getting treatments to patients more quickly is definitely a good thing, a recent blog from Context Matters points out that, based on its calculations, the FDA’s previously established programs to expedite therapies (including Fast Track, Accelerated Approval, and Priority Review) have not produced lasting improvements in approval time. “Based on our preliminary analysis, in 2008 the average cycle time for ‘Priority’ was 10.1 months, versus the ‘Standard’ which was 21.2 months. In 2011, the average cycle time for ‘Priority’ was 19.5 months, versus ‘Standard’ which was 17.5 months,” the blog authors wrote. “What’s interesting here is that over time the fast lane has apparently become just another standard lane; in 2011 it was actually even slower.”

The group at Context Matters compared the process in the United States to that of the one used by the European Medicines Agency (EMA) and concluded that despite not having “fast” or “standard” designations, the EMA approval process took an average of just 3.5 months during 2012.

The FDA needs to have the proper infrastructure and support to successfully reduce approval times, says Peter Pitts, a former head of communications for the FDA who is a board member of Context Matters and co-founder of the Center for Medicine in the Public Interest. “Clearly, when you are looking at products that have less data behind them, you need more senior people who can devote greater resources to studying them, and that also takes time away from other programs that the agent needs to review,” Pitts told Specialty Pharmacy Times. “It’s one thing to give the FDA more authority, it’s another thing to give the FDA greater responsibility, but if you don’t give them the resources to get it done, to a large degree it is just rhetoric.”
 
Despite the improvements in communication and collaboration between drug developers and the FDA, manufacturers still must overcome many hurdles on the way to getting therapies approved by the agency. Sponsors must have more resources available in less time in order to push their therapies through the abbreviated regulatory process, and because many of the drugs being submitted for review under the new designation are targeted therapies, they frequently must be developed in concert with a companion diagnostic test. Such diagnostics would have to be approved separately by the FDA’s Center for Devices and Radiological Health, and guidance governing their development has been shaky so far.

Once therapies gain approval through the breakthrough therapy program, they still may face challenges in getting to patients as health plans may be reluctant to provide reimbursement for therapies with a limited amount of evidence regarding patient outcomes. Other issues that may thwart successful market penetration of drugs traveling through this pathway include timing of facility inspections and obtaining drug approval in other countries (where the breakthrough designation is not recognized or accepted). A lack of FDA resources may also affect the success of the breakthrough pathway in getting therapies to patients with few or no treatment options.

But, speed to market isn't the only metric that matters, Pitts points out. "Breakthrough designation doesn’t always mean the product gets approved...sometimes it means that because you fail faster, you don’t waste money on programs that don’t pan out."

  Read More & Comment...

High and Mighty

07/31/2013 07:16 AM |

The Washington Post reports Capital City Care dispensary sold Washington DC’s first legal marijuana “in at least 75 years” on Monday. The sale is a result of a “15-year struggle to legalize medical marijuana in the district,” the culmination of a battle that “dates to the mid-1990s, when HIV/AIDS activists first fought to put medical marijuana on the citywide ballot.” About 70% of DC voters approved a 1998 legalization initiative, only to have it squashed by Congress for over a decade. But after Congress lifted the restriction in 2009, it still took several years for the city government to establish a “strict regulatory and licensing regime limited to city residents with specific chronic illnesses,” while also minimizing the “risk of future federal intervention.”

  Read More & Comment...

NEHI and a mile wide

07/30/2013 06:13 AM |

The New England Health Institute has released a new report calling on public and private policymakers to adopt six “priorities for action” to improve the way patients take their prescription medicines across the US.

NEHI has created six “priorities for action” to improve the way patients take their prescription medicines across the US. They are: 

1) Promote sharing of best practices and lessons learned from pilots of new medication management techniques

2) Support large-scale implementation of promising, evidence-based “tactics” for improved medication management

3) Continue development of metrics of medication use that will spur adoption of proven medication management strategies

4) Support continued rapid adoption of electronic prescribing and electronic medical records with capabilities that support evidence-based interventions for improved adherence

5) Continue to improve Medication Therapy Management services in Medicare Part D including improvements in program services and targeting; consider wider adoption of medication management by other health care payers

6) Integrate medication adherence research, policy development and advocacy with broader efforts that aim to improve use of medicines, including those focused on patient safety

The report concludes:

Proponents of better patient adherence should rally behind a comprehensive vision of good medication use that encompasses interventions to promote adherence, and promote a vigorous agenda for policy change that will create incentives for proven adherence interventions.

Words to the wise.

  Read More & Comment...

Howard Dean sees the light?

07/30/2013 05:02 AM |

Howard Dean on IPAB:

One major problem is the so-called Independent Payment Advisory Board. The IPAB is essentially a health-care rationing body. By setting doctor reimbursement rates for Medicare and determining which procedures and drugs will be covered and at what price, the IPAB will be able to stop certain treatments its members do not favor by simply setting rates to levels where no doctor or hospital will perform them.

There does have to be control of costs in our health-care system. However, rate setting—the essential mechanism of the IPAB—has a 40-year track record of failure. What ends up happening in these schemes (which many states including my home state of Vermont have implemented with virtually no long-term effect on costs) is that patients and physicians get aggravated because bureaucrats in either the private or public sector are making medical decisions without knowing the patients. Most important, once again, these kinds of schemes do not control costs. The medical system simply becomes more bureaucratic.

The nonpartisan Congressional Budget Office has indicated that the IPAB, in its current form, won't save a single dime before 2021. As everyone in Washington knows, but less frequently admits, CBO projections of any kind—past five years or so—are really just speculation. I believe the IPAB will never control costs based on the long record of previous attempts in many of the states, including my own state of Vermont.

Read the full piece in the Wall Street Journal.

  Read More & Comment...

Arrant Transparent

07/29/2013 09:07 AM |

Speaking of clinical trial data transparency – here’s an excellent analysis from the August edition of the Burrill Report ...

Fight for Transparency Heats Up: Industry turns to courts to stop policy in EU, offers own approach

Daniel S. Levine

Tom Jefferson had nagging concerns about his review for the Cochrane Collaboration of clinical studies of the flu drug Tamiflu, but they crystallized in 2009 when a Japanese pediatri­cian raised a question about the work via email. The doctor want­ed to know why the review in­cluded eight unpublished trials that Jefferson and his colleagues hadn’t seen, and had only been included as summaries in an­other study funded by the drug’s producer Roche?

The solution seemed simple enough. Jefferson, an epidemi­ologist based in Rome who was conducting the updated analy­sis for the Cochrane Collabora­tion, an independent group that provides guidance to health­care professionals on the use of drugs, would reach out to the authors of the studies and get them. But the authors either told him they didn’t have the data, said they had never seen the data, or ignored him completely. When he asked Roche for the studies, it said it would provide them, but insisted at first that he sign a confidentiality agree­ment, a condition that he found unacceptable.

The controversy came against a backdrop of worldwide fear of a global pandemic of bird flu that sent the World Health Or­ganization, the Centers for Dis­ease Control and Prevention, and governments around the world spending billions of dollars to stock­pile Tamiflu. Despite the spending, Jefferson says there were questions about whether the drug did anything to prevent transmission of flu, mini­mize complications, or whether the health benefits the drug provided jus­tified the risks of using it. Roche, in a statement posted on its web site and updated at the end of February 2013, said that it had disagreed with the analysis plan Cochrane Collaboration shared with it because it was at odds with how Tamiflu has been reviewed and approved by regulatory authori­ties in more than 80 countries. The company said it stood by the “robust­ness and integrity” of its data support­ing the safety and efficacy of the drug.

“The fight for the last four years hasn’t been so much for clinical study reports,” Jefferson says, “but to have clinical study reports without having to sign confidentiality agreements, funny handshakes, rolling up our trouser leg, and so on.”

The four-year battle to obtain clini­cal trials data—he believes that there have been 123 studies (74 of which Roche sponsored)—has made Jeffer­son a flag bearer in an international fight over clinical trials data transpar­ency. The controversy, which is by no means limited to Tamiflu and Roche, is now reaching a critical point. A le­gal battle is underway in Europe over a European Medicines Agency trans­parency policy expected to take effect at the start of 2014 that would make public clinical trial data once a drug is approved. At the same time, in the United States, the Institute of Medi­cine is at work on a consensus study on the issue and the U.S. Food and Drug Administration is seeking com­ment on a clinical data transparency policy of its own.

Much is at stake as the policymak­ers embrace comparative effectiveness and the advent of Big Data provides a new means to ferret out untapped information hidden within clinical study reports—the detailed narrative reports at the individual patient level that can run to tens of thousands of pages in a single trial.

Proponents of clinical data transpar­ency argue that it will provide doctors with greater insight into the safety and efficacy of the drugs they prescribe, improve care, cut waste, and minimize scientific misconduct and fraud. Peter Doshi, a post doctoral comparative ef­fectiveness researcher at Johns Hop­kins University, who is also working on the Tamiflu review for the Cochrane Collaboration, points to a list of block­buster drugs that were marketed only to have significant health risks come to light through academicians analyzing clinical trials data. “The whole system has depended on trust in medicine, trust in people to report properly, trust in people to have enough information to credibly analyze trials,” he says. “We know enough not to be so trusting anymore.”

Industry, while not of one mind, says that in principle it doesn’t oppose transparency, but expresses concerns about how it is done. These concerns include the threat to confidential com­mercial information, the challenge to the authority of regulators, the risk to patient privacy, and the opening of the data to inappropriate uses that could lead to the publication of misleading results and public health scares.

Lawsuits in Europe

In May, the General Court of the European Union prohibited the Euro­pean Medicines Agency from releas­ing data from two AbbVie and Inter­mune trials in an interim ruling, part of a challenge by the two drugmakers to the agency’s decision to grant access to information the companies provid­ed as part of their market approval ap­plications. The challenge is the first to be made to the EMA’s three-year old access-to-documents policy.

Since November 2010, the Agency has released more than 1.9 million pages in response to such requests. The legal battle involves documents relat­ing to AbbVie’s rheumatoid arthritis drug Humira and InterMune’s Esbriet, a treatment for idiopathic pulmonary fibrosis, an unexplained chronic and progressive scarring of the lungs. In both cases, competitors of the compa­nies were seeking the data.

“Biopharmaceutical companies support responsible data sharing that protects patient privacy, maintains the integrity of the regulatory review pro­cess, and preserves incentives for bio­medical research,” said Matt Bennett, senior vice president for the Pharma­ceutical Research and Manufacturers of America in a statement at the time. “Unfortunately, the EMA’s current and proposed policies fail to respect these principles.”

The ruling comes amid increasing pressure from medical journals and patient advocates on pharmaceutical companies to provide complete trans­parency and make public all of their clinical trials data. It also comes as the EMA readies implementation of a new policy to proactively publish data from clinical trials supporting the approval of new drugs once a decision has been made. The EMA said it would continue the process of drafting its policy on publication of clinical trials data.

Ben Goldacre, author of “Bad Phar­ma” and co-founder of the AllTrials campaign, which seeks publication of all results from all clinical trials, called the ruling “a disgrace.” “There is no justification for withholding informa­tion about the methods and results of clinical trials from doctors, research­ers, payers and patients, who need all the information on a medicine to make truly informed decisions,” he says.

The EMA says it welcomes the op­portunity for legal clarification of the concept of commercially confidential information, but expressed “regret” over the decision to grant interim re­lief to AbbVie and InterMune.

FDA, IOM, weigh transparency

In the United States, although ef­forts to bring about transparency have moved slower, they are advancing. In October 2012, the Institute of Medicine held a two-day workshop to explore the benefits of sharing clinical research data, the issues surrounding it, and how best to do so. The IOM is now working on a consensus study that some hope could provide a roadmap for the devel­opment of a clinical trials data transpar­ency policy in the United States.

A group of leading pharmaceutical and biotechnology companies has been involved in the IOM process and issued a press release hailing the effort. “This industry group is strongly in support of enhanced access by third party re­search to clinical trial data generated by industry and academia in a manner that ensures that patient confidential­ity is preserved, scientific integrity is maintained, and intellectual property rights and confidential company infor­mation are protected,” they said in a joint statement.

The Food and Drug Administration is seeking public comments through August 5 on a policy to make available de-identified and masked data derived from medical product applications. But advocates of transparency say such data will be of limited utility because the policy under consideration would de-identify it and remove the data’s link to a specific product, study, or application.

Peter Pitts, president of the Cen­ter for Medicine in the Public Interest and chairman of a conference on clini­cal trials data transparency held by FDANews July 23-24, says it’s “a non-arguable fact that FDA is at the nexus of vast amounts of clinical data that if it was appropriately shared it would be of tremendous value.” He says that sharing information, among other things, could help companies fail faster, which would save a lot of money and allow for reinvestment of diminishing resources. But such an effort, he says would require information technol­ogy resources the agency is without, decisions on what is and isn’t redacted, discussions about intellectual property rights and commercial confidentiality, and funding for it all.

“We’ve come to the point now, rela­tive to clinical trials data, that transpar­ency is a good thing. The question now becomes, ‘How do you accomplish that and what exactly does transparency mean? And how quickly does it be­come transparent? And how much of it becomes transparent and how much of it remains confidential? Is it transpar­ent through corporate entities, or is it transparent through a consortium of corporations? Is it transparent through a government organization? And who ultimately decides? Can people opt out? And if people opt out, can you really have transparency?’” says Pitts. “They are all very tough questions.”

(Note: For more on the FDA News conference, see Cry “havoc,” and let slip the dogs of data transparency.

Progress, but no victory

Four years after Jefferson began his efforts to access clinical study reports from Roche and GlaxoSmithKline, which produces the Tamiflu competi­tor Relenza, both of which are in the class of drugs known as neuramini­dase inhibitors, it is Roche and GSK that arguably have the clearest defined and most advanced efforts to provide clinical trials data to outsiders.

Roche has complied with the origi­nal request the Cochrane reviewers made in 2009, although the researchers continue to pursue access to additional trials data of which they subsequently learned. The Cochrane Collaboration expects at the start of 2014 to publish a new review of neuraminidase inhibi­tors based on 23 clinical studies on Re­lenza and up to 20 studies on Tamiflu.

In February, GSK announced it had signed on in support of the AllTri­als campaign and has vowed to pub­lish clinical trials data of all approved drugs dating back to 2000, the date the company was formed through the merger of Glaxo Wellcome and Smith­Kline Beecham.

“We are committed to being trans­parent with our clinical trial data to help advance scientific understanding and inform medical judgment,” Patrick Vallance, President, Pharmaceuticals R&D, GlaxoSmithKline, said in an­nouncing support for the campaign. “Our commitment also acknowledges the very great contribution made by the individuals who participate in clin­ical research. All those involved in the conduct and publication of clinical re­search, whether healthcare companies like GSK, academia or research organi­zations, have a role to play in ensuring that the data they generate are made publicly available to help bring patient benefit.”

In response to questions from The Burrill Report, GSK said it believes a broader solution for providing access to trial data from across the research com­munity needs to be developed and it has been in discussion with trials sponsors from industry, academia, and research charities working in partnership to cre­ate one. GSK says one solution would be the establishment of an independent data custodian to which research spon­sors would deposit anonimized data after a project has been completed and clinical studies are published. Research­ers could then submit scientific propos­als and analysis plans to independent custodian to request access.

The Pharmaceutical Research and Manufacturers of America and the Eu­ropean Federation of Pharmaceutical In­dustries and Associations at the end of July jointly issued a list of principles for clinical trial data sharing. They call for a voluntary plan that would make data available to only to “qualified” research­ers who sign non-disclosure agree­ments. They say they would only share data for which they have the informed consent of study participants to do so.

(Note: The full principles can be found on the PhRMA website. PhRMA said implementation of the commitments in the principles will begin on January 1, 2014.)

Companies will start reviewing requests for data from researchers at that point, but Castellani said companies will need to take into account patients’ informed consent. He said it will not be possible to share data from many earlier trials because patients participating in them did not consent to such release.)

But advocates worry that the vic­tories in studies extracted from phar­maceutical companies to date may be short lived, in large part due to the legal battle in Europe over the EMA’s transparency policy. “Societal expec­tations have dramatically moved in a direction of greater transparency, but there remain serious risks to the pro­cess that could potentially derail a lot of the progress that has been made,” says Johns Hopkin’s Doshi. “The prog­ress we’ve seen with Tamiflu may have been a one-off victory for what other­wise may be a return of data secrecy. Many people think the goals of trans­parency have been achieved, but they have not.”

  Read More & Comment...

Nowhere to go but down

07/26/2013 04:09 AM |

Via Politico:

ANOTHER DAY, ANOTHER POLLING NADIR FOR OBAMACARE - This time, the bad news for the White House came from CBS, which found that 39 percent of respondents want the law wiped from the books, the highest percentage since the broadcaster began asking the question. That's compared to 36 percent who want to keep or expand the law. Recent polls have tended to show the law mired in continued uncertainty and unpopularity among Americans, a dynamic supporters hope will start to shift once the key benefits of the law come online in January.

  Read More & Comment...

Cry "havoc" and let slip the dogs of data transparency

07/24/2013 09:09 AM |

How about "translational transparency?"

Yesterday I had the privilege to chair the Clinical Trials Disclosure and Transparency Summit.

Here are my opening remarks:

Simplistic solutions to important public health issues are generally wrong, often deleterious to the issue at hand --and often hide political versus public health agendas. Or as Henry Kissinger once said:

”The real distinction is between those who adapt their purposes to reality and those who seek to mold reality in the light of their purposes.”

And so, with that introduction, welcome to the Clinical Trial Disclosure and Transparency Summit.

In a recent op-ed in the New York Times, biasedly titled, Health Care’s Trick Coin, Ben Goldacre (the author of the neutrally titled book, Bad Pharma: How Drug Companies Mislead Doctors and Harm Patients, made a number of serious allegations – and factual mistakes in his discussion of clinical trial transparency – specifically that the Clinicaltrials.gov registration requirement in FDAAA isn't being implemented and that only “full transparency and publication of clinical trial will address the issue.” It’s not so simple – and the facts matter.

As the former senior government official in charge of clinicaltrials.gov, it’s important to look at the facts – and the numbers.

In 2000, the National Institutes of Health (NIH) launched ClinicalTrials.gov to provide public access to information on clinical studies.  Although it initially contained information primarily on NIH-funded research, it has been expanded to include both publicly and privately supported clinical research. 

Since the launch of the site, it has been enhanced to significantly increase data sharing. The ClinicalTrials.gov database includes information on nearly 140,000 clinical trials in all 50 states and 182 countries. 

Is anyone accessing this wealth of information? Yes!  The NIH reported last year that ClinicalTrials.gov “receives more than 95 million page views per month and 60,000 unique visitors daily.

Facts do not cease to exist because they are ignored. Mr. Goldacre should realize that reality, although sometimes inconvenient to ones argument, remains reality.
As we progress through the next two days, here are some issues we will consider:

·      The FDA is at the nexus of vast amounts of patient-level clinical data – what role will transparency play in making such information available? How might the agency accomplish such a task, how would it be funded – and where does such an initiative fall on the agency’s long list of urgent priorities?

·      How will current AbbVie/Intermune legal decision in the EU impact transparency issues here at home?

·      How will the IOM report impact how we view transparency going forward? Indeed – how will the IOM move forward on this issue – or will it?

·      Should transparency be a government dictate or a working collaboration between interested parties both private and public – and what role should patients play. Should there be formalized transparency consortia? Should it be global?

·      What are the implications for intellectual property and the connected question of incentivizing (or dis-incentivizing) investment in innovation? Is transparency a Trojan horse to attack patents and intellectual property rights?

·      How can we avoid making transparency a game of “gotcha” such as what happened at the 2010 Avandia hearing where a grandstanding Henry Waxman pointed his finger at the GSK research chief and stridently said, “do you swear under oath that you will make all clinical trial data available? Only to get the embarrassing response, “Congressman, it’s available right now at www.gsk.com.”

·      What about the availability of data from unpublished negative trials? Why aren’t payers asking for these before they make reimbursement decisions? For those of you following the debate over FDAMA 114 and the use of pharmaco-economic data for reimbursement decisions, this shouldn’t be an unfamiliar discussion. Can a free-market solutions drive transparency?

·      Can transparency become a competitive advantage as well as a public health imperative?

After all, good things happen when everybody wins.

Ladies and Gentlemen – start your engines.

The Summit’s first speaker was Dr. Richard Moscicki, CDER’s new Deputy Director for Science Operations. His presentation focused on the transparency dichotomy of “the promise versus fear and loathing.”

As to “why” transparency, he offered reproducibility, re-analysis the potential to identify new information (placebo effects, biomarkers, endpoints, trial designs).

And then his talk got interesting. He laid it on the table that one group that is silently against transparency is academics – because they don’t want to be cornered into making studies public if it impacts their ability to publish.

The FDA’s impediments to data sharing, according to Moscicki are (1) Legal (data ownership, HIPAA/privacy, proprietary information), (2) technical/practical (format, data standards, CDISC, redaction), (3) Resources and, (4) the agency’s need to focus on its key mission.

Per that last point, he honestly shared that the FDA does not view (at least at as of right now) the issue of clinical trial data transparency as a key agency agenda item – unless there was move to move it to the head of the regulatory queue via user fees. (That would be DTUFA – Data Transparency User Fee Act. Folks – you heard it here first.)

But transparency is important and, per Moscicki, “inevitable” – and to that end he discussed the agency’s recent Federal Register Notice (Masked and De-identified Non-Summary Safety and Efficacy Data).

FDA invites comments on the issues it should consider with respect to the availability of clinical and pre-clinical study data after steps have been taken to “de-identify” it by removing any personally identifiable information and “mask” it by removing data that could link it to a specific application or sponsor. Specifically, the agency is interested in comments from the public on the following topics:

– What factors should be considered in masking study data (e.g. should certain data fields be removed or modified; number of different products to pool within a class)?

– Should there be any limitations on the agency’s ability to make masked data available?

– In addition to current FDA requirements to remove any names and other information that might identify patients, what other information should FDA consider when de-identifying the data?

– Would regulatory changes facilitate the implementation of this proposal?

– In what situations would disclosing masked data be most useful to advance public health?

Moscicki stressed that FDA’s approach has been under development for several years and

* It is not linked to EMA proposal;

* FDA is not contemplating routine preparation and release of de-identified and masked clinical and non-clinical study data;

* The agency is encouraging independently organized efforts to create, curate and share clinical trial datasets from all sources.

Dr. Moscicki’s complete PowerPoint presentation can be found here.

Next up on the agenda was Sir Alasdair Breckenridge, former Chairman of the MHRA and currently the Chair of United Kingdom’s Department of Health Emerging Science and Bioethics Advisory Committee.

Sir A. challenged the assemblage with the statement that transparency is “a process without a beginning or an end. It is a continuum.” And, “Transparency is like feeding a hungry dog – you more you give it, the more it wants.”

Cry havoc – and let slip the dogs of data transparency.

His presentation focused on four key questions:

(1) Should the public have access to data on which regulatory decisions are taken?

(2) What are the advantages and disadvantages of increased transparency?

(3) What are the key distinctions between transparency and communication (specifically the issue of public health literacy and numeracy – and the “road testing” of released information)?

(4) Will increased transparency lead to increased trust in regulators and industry?

On that last point, Dr. Breckenridge pointed out at increased transparency does not lead to increased trust. Trust depends on perceptions of honesty and competence, and transparency may expose inherent inefficiencies in a system. And that’s a good thing – if we really mean to make the most of transparency.

Transparency cannot be “for thee but not for me.”

He offered five keystones for moving forward:

(1) Agreement on timing of release of information

(2) Agreement on nature of information to be released

(3) Standards of protection of personalized data

(4) Standards for meta-analyses

(5) Rules of engagement for observational studies

He also discussed the EMA’s mad dash towards data transparency and the severe blow it was dealt by the legal victory of AbbVie and Intermune. A lesson that should be noted by the Ben Goldacres's of the world -- and the British Medical Journal.

Sir Alasdair’s PowerPoint presentation can be found here.

Maybe the FDA’s incremental and collaborative approach is best after all. Slow and steady ain’t sexy – but it generally works best -- and is in the best interest of the public health.

  Read More & Comment...

FDAMARama

07/23/2013 06:54 AM |

According to a report in the Pink Sheet, “Spurred by increasing stakeholder requests for clarity, FDA may be moving toward developing guidance on how and when drug firms can provide health care economic data to formulary managers.”

Per an FDA spokesperson “This is one of the areas that is of interest to FDA and we are discussing possible guidance development.”

The guidance could help clarify the regulatory parameters around the provision in the FDA Modernization Act of 1997 that allows drug companies to proactively disseminate health care economic information to formulary committees within certain limitations. Sec. 114 requires that such information be supported by “competent and reliable scientific evidence” and that any health economic information disseminated must “directly relate” to a drug’s approved indication.

As payers push for more information on the cost effectiveness of drug treatment, manufacturers are taking a closer look at Sec. 114 and are seeking direction from the agency on how it could be used. FDA Office of Prescription Drug Promotion Director Tom Abrams recently acknowledged heightened stakeholder interest in guidance on appropriate communications under FDAMA Sec. 114. “We know that’s a hot topic – what goes to formulary committees and similar bodies,” he said on June 25at the DIA annual meeting in Boston.

Abrams identified dissemination of health care economic information as one of four topics the agency is “exploring for future guidance development.” The other three are medical practice guidelines, comparative claims and “scientific exchange.”

Abrams’ DIA remarks are the first inkling of Agency movement since late 2011 when, according to a notice in the Federal Register:

The Food and Drug Administration (FDA) is announcing the establishment of a docket to assist with our evaluation of our policies on communications and activities related to off-label uses of marketed products, as well as communications and activities related to use of products that are not yet legally marketed for any use, we would like to obtain comments and information related to scientific exchange.  FDA is interested in obtaining comments and information regarding scientific exchange about both unapproved new uses of products already legally marketed (“off-label” use) and use of products not yet legally marketed for any use. 

And the issue of “scientific exchange” comes front and center. According to the FR notice, To assist with our evaluation of our policies on communications and activities related to off-label uses of marketed products, as well as communications and activities related to use of products that are not yet legally marketed for any use, we would like to obtain comments and information related to scientific exchange.

The FR notice puts this request into perspective:

On July 5, 2011, a citizen petition was submitted by Ropes & Gray and Sidley Austin LLP on behalf of seven product manufacturers (Petitioners):  Allergan, Inc.; Eli Lilly and Co.; Johnson & Johnson; Novartis Pharmaceuticals Corp.; Novo Nordisk, Inc.; Pfizer, Inc.; and sanofi-aventis U.S. LLC under 21 CFR 10.30.  The citizen petition requested that FDA clarify its policies for drug products and devices governing certain communications and activities related to off-label uses of marketed products and use of products that are not yet legally marketed for any use.  Specifically, the petition requests clarification in the following areas:
 

1.  Manufacturer responses to unsolicited requests; 

2.  Scientific exchange; 

3.  Interactions with formulary committees, payers, and similar entities; and

4.  Dissemination of third-party clinical practice guidelines.

For some time, FDA has been considering these issues and is currently evaluating our policies on sponsor or investigator communications and activities related to off-label uses of marketed products and use of products that are not yet legally marketed for any use.  We have been considering what actions to take in the areas specified by the petitioners with respect to manufacturer responses to unsolicited requests; interactions with formulary committees, payors, and similar entities; and the dissemination of third-party clinical practice guidelines.

Specifically, the FDA asks:

• How should FDA define scientific exchange?  

• What types of activities fall under scientific exchange?

• What types of activities do not fall under scientific exchange?

• Are there particular types and quality of data that may indicate that an activity is, or is not, scientific exchange?

• In what types of forums does scientific exchange typically occur?  Should the use of certain forums be given particular significance in determining whether an activity is scientific exchange or an activity that promotes the drug or device?  If so, which forums?

• What are the distinctions between scientific exchange and promotion?  What are the boundaries between scientific exchange and promotion?

•  Generally, who are the speakers involved in scientific exchange, and who is the audience for their communications?

• Should the identity of the participants (either speakers or audience) be given particular significance in determining whether an activity is scientific exchange or an activity that promotes the drug or device?  If so, which participants would be indicative of scientific exchange and which would be indicative of promotion?

• How do companies generally separate scientific roles and promotional roles within their corporate structures?

• How should the Agency treat scientific exchange concerning off-label uses of already approved drugs and new uses of legally marketed devices? Please address whether there should be any distinctions between communications regarding uses under FDA-regulated investigation (to support potential approval) and communications regarding uses that are not under express FDA-regulated investigation.

• How should the Agency treat scientific exchange concerning use of products that are not yet legally marketed (that is, products that cannot be legally distributed for any use outside of an FDA- or institutional review board (IRB)-approved clinical trial)?

• Should investigational new drugs and investigational devices be treated the same with respect to scientific exchange? Why or why not? 

• Under 21 CFR 812.7(b), an investigational device is considered to be “commercialized” if the price charged for it is more than is necessary to recover the costs of manufacture, research, development, and handling.  Similarly, FDA considers charging a price for an investigational drug that exceeds that permitted under its regulations (generally limited to cost recovery) to constitute “commercialization” of the drug (see 74 FR 40872 at 40890, August 13, 2009; 52 FR 19466 at 19467).  What other actions indicate the commercialization of drug and/or device products?  If there are differences in the steps taken to commercialize drug products and the steps taken to commercialize device products, either before or after approval, please explain these differences.

A lot of questions and, it seems, a lot of potential regulatory mission creep.

Relative to, “Interactions with formulary committees, payors, and similar entities,” the door is now also open for debate on FDAMA Section 114 and health economic data.

There is no on-the-books draft or final guidance on Section 114. It’s been 14 years since the initial language. Health-related quality of life claims are considered under the established "adequate and well-controlled trials" standard.

Some background to put this into perspective:

To address concerns that FDA regulations were limiting the dissemination of outcomes research, Congress added Section 114 to set a new, less stringent standard applicable to promotional dissemination of health care economic information to MCO formulary committees: "competent and reliable scientific evidence."

Even though there is no FDA guidance to explain the agency's understanding "competent and reliable scientific evidence,” PhRMA developed a draft guidance, which was submitted to the FDA in June 1998. In its draft, PhRMA sought input from the International Society for Pharmacoeconomics and Outcomes Research, the Society for Medical Decision Making, the Academy of Managed Care Pharmacy, the American Pharmaceutical Association, and other groups.

In its submission to the FDA, PhRMA explained the history behind Section 114 and proposed guidance on the following terms used in the new law:

• Health care economic information.
• Managed care or other similar organizations.
• Formulary committee or other similar entity.
• Directly related to an approved indication.
• Competent and reliable scientific evidence.

The PhRMA proposal took an approach to interpretation consistent with Congress's intent that Section 114 would increase the dissemination of outcomes research information by product manufacturers to MCOs. PhRMA concluded that the term "health care economic information" should include all forms of economic analysis so the guidance could adapt to new and evolving outcomes research methods.

One of the phrases in Section 114 that is difficult to interpret is that promotion must involve a claim that "directly relates to an indication approved [by the FDA]." In the draft guidance, PhRMA proposed that extrapolation from data included on labeling would be appropriate at least under the following circumstances: from duration of use in labeling to actual duration of use found in pharmacy databases, from dosages included in labeling to actual dosages found in pharmacy databases, and from controlled trial settings to actual practice settings.

The standard set by Section 114, "competent and reliable scientific evidence," is the same standard used by the Federal Trade Commission (FTC) when assessing the adequacy of substantiation for manufacturer claims involving OTC drugs and products affecting environmental health. That standard requires transparency of methods and use of methods accepted by experts in the field. In its proposal, PhRMA recommended that the FDA follow long-established FTC interpretation of the competent and reliable scientific evidence standard.

The full FR Notice on "Communications and Activities Related to Off-Label Uses of Marketed Products and Use of Products Not Yet Legally Marketed; Request for Information and Comments" can be found here.

In October 2012, PhRMA issued a white paper, asking the FDA for guidance on the supporting evidence drug companies need for the health care economic data they send to formulary managers should specifically allow for use of a range of data sources, not limited to adequate and well-controlled clinical trials.

The white paper urges the agency to develop formal regulatory guidance on Sec. 114 of the FDA Modernization Act of 1997, which allows drug companies to proactively disseminate health care economic information to formulary committees within certain limitations.

The white paper outlines a number of data elements that should satisfy the competent and reliable scientific evidence standard. They include: methods for establishing economic costs and consequences that are widely accepted by experts in the field using a clear, pre-defined study protocol; an “accurate and balanced assessment of the economic consequences of a drug therapy, consistent with the current weight of credible evidence”; a representative study population; and information that allows the reader to determine how the research was conducted.

PhRMA recommends that FDA allow the competent and reliable standard to be satisfied with data obtained through a number of different methods, including observational study designs, database reviews and other economic modeling techniques. “There should be no pre-specified number or type of study required to substantiate a claim."

For example, “a claim that a drug is more cost-effective than a competing drug may be made where the cost savings are due to reduced resource utilization resulting from improved efficacy outcomes, decreased administration or monitoring costs, or where the difference in cost is due to the drug causing fewer adverse events, as long as these differences are supported by competent and reliable evidence.”

PhRMA argues that FDA should not consider such a statement a comparative clinical claim, which would trigger the “substantial evidence” requirement involving clinical trials.

Companies should be permitted to disseminate data on the “real world” economic implications of a therapy on health outcomes, according to the white paper. For example, “if a manufacturer conducts a competent and reliable study investigating the impact of a drug indicated for the treatment of diabetes mellitus on costs associated with cardiovascular care, the manufacturer should be permitted to proactively disseminate such data to appropriate audiences.”

Tom Abrams’ comments should act as more than a passing notice. Folks – it’s time to step up to the plate – the implications for payers and academic detailing are both timely and significant.

  Read More & Comment...

ObamaCare Flunks AP Exam

07/22/2013 06:26 AM |

From that well-know Tea Party mouthpiece – the Associated Press …

FACT CHECK: Obama spins health insurance rebates

WASHINGTON (AP) - Another year, another round of exaggeration from President Barack Obama and his administration about health insurance rebates.

In his speech defending his health care law Thursday, Obama said rebates averaging $100 are coming from insurance companies to 8.5 million Americans. In fact, most of the money is going straight to employers who provide health insurance, not to their workers, who benefit indirectly.

Obama danced around that reality in remarks that also blamed problems in establishing affordable insurance markets on political opponents, glossing over complex obstacles also faced in states that support the law.

A look at some of his claims and how they compare with the facts:

-"Last year, millions of Americans opened letters from their insurance companies. But instead of the usual dread that comes from getting a bill, they were pleasantly surprised with a check. In 2012, 13 million rebates went out, in all 50 states. Another 8.5 (million) rebates are being sent out this summer, averaging around 100 bucks each."

- After introducing several people who got rebate checks last year: "And this is happening all across the country. And it's happening because of the Affordable Care Act. Hasn't been reported on a lot. I bet if you took a poll, most folks wouldn't know when that check comes in that this was because of Obamacare that they got this extra money in their pockets. But that's what's happening."

-" If they're (insurers) not spending your premium dollars on your health care - at least 80 percent of it - they've got to give you some money back."

THE FACTS: Just as he did a year ago, Obama made a splashy announcement about rebates that incorporates misleading advertising.

The health care law requires insurance companies that spend too much on administrative expenses to issue rebates to customers. But those customers are often employers that in turn offer insurance to workers and bear the bulk of the costs. In workplace plans, the rebate goes to the employer, which must use it for the company health plan but does not have to pass all or part of it on to the worker. People who buy their own insurance and qualify for a rebate get it directly.

Obama was on solid ground in saying "millions of Americans" got rebate checks last year, but the number was not close to 13 million as he implied.

Of the 12.8 million rebates announced last year, health policy experts estimated 3 million would go directly to the insured. The government didn't know how many.

Nearly two-thirds of the 12.8 million were only entitled to pro-rated and decidedly modest rebates, because they were covered by employers that pay most of their premiums. Workers typically pay about 20 percent of the premium for single coverage, 30 percent for a family plan. Employers pay the rest.

And employers can use all the rebate money, including the workers' share, to benefit the company health plan, perhaps restraining premiums a bit or otherwise improving the bottom line. The law requires insurers to spend at least 80 percent of premiums they collect on medical care and quality improvement, or return the difference to consumers and employers.

Altogether, this year's rebates are worth $500 million, down from $1.1 billion returned last year. The government says the lower rebates mean insurance companies are becoming more efficient.

-"I'm curious, what do opponents of this law think the folks here today should do with the money they were reimbursed? Should they send it back to the insurance companies?"

THE FACTS: Even in that unlikely event, most people could not send it back to insurance companies because the money doesn't go "in their pockets" and they have no control over what their employers do with it.

-"In states that are working hard to make sure this law delivers for their people, what we're seeing is that consumers are getting a hint of how much money they're potentially going to save because of this law. In states like California, Oregon, Washington, new competition, new choices, market forces are pushing costs down."

THE FACTS: It is simply not known whether health insurance will become less expensive in those states - or nationally than it is now, or than it would have been absent the law. And hitches in setting up the new insurance marketplaces called exchanges are not limited to Republican-led states where leaders object to the law, although that political pushback is certainly part of what's going on.

In California, for example, where there is plenty of competition by health insurers wanting to get into the exchange, an actuarial report commissioned by Covered California, the state agency running the insurance marketplace, found that middle-income residents could see individual health premiums increase by an average of 30 percent while costs go down for lower income people.

In West Virginia, Democratic Gov. Earl Ray Tomblin - also a cooperative partner in expanding Medicaid and setting up an exchange - complained to federal officials this week about delays in rules and guidelines from Washington as the state struggles to meet deadlines under the law.

"Many West Virginia families have expressed frustration" trying to find out how much policies from the exchange will cost them and whether they will get a subsidy, he said, and the state is "dangerously close" to falling short of requirements under the law.

  Read More & Comment...

Commerce Claws

07/19/2013 06:24 AM |

In case you had any doubt that Indian policy on pharmaceuticals isn’t predicated on domestic manufacturing policy …

A day after a high-level panel headed by Prime Minister Manmohan Singh relaxed foreign direct investment (FDI) norms in sectors ranging from telecom to single brand retail, he’ll be holding a separate meeting to review the policy in the pharmaceutical sector.

According to a senior official, "The main concern of the Ministry of Commerce and Industry is that a stage might come when India might not have a company ready to manufacture drugs on behalf of the government, even if the provision of compulsory license is invoked.”

Shouldn’t the fact that acquiring companies are paying huge valuations -- many time the cost of setting up new projects -- raise a question as to their motivation – and that of the Indian government?

  Read More & Comment...

China moves on Gleevec

07/18/2013 07:01 AM |

Another example of domestic manufacturing policy trumping the public health?

It took only two months after patent expiry in China for two generic versions of Novartis AG’s blockbuster chronic myeloid leukemia drug Glivec (imatinib) (marketed as Gleevec in the U.S.) to gain China FDA approval, and many more are expected to follow suit. But Novartis plans to fight back by highlighting the quality and efficacy of its brand and its long-running patient assistance program.

Two companies received CFDA approval June 26, Jiangsu Hansoh Pharmaceutical Co. Ltd. and Jiangsu Chia-tai Tianqing Pharmaceutical Co. Ltd., or CTTQ, 60% of which is held by Hong Kong-listed Sino Biopharmaceutical Ltd. CTTQ holds the first capsule generic approval, while Hansoh received CFDA approval for a tablet formulation of imatinib. Generic imatinib for chronic myeloid leukemia will launch in August, Sino Biopharmaceutical said during a July 4 event.

Although the Glivec compound patent expired in China in April, Novartis still holds a beta crystalline patent in the country until 2018 and a patent for a gastrointestinal stromal tumors indication until 2021, Novartis China said. According to Novartis, the two China generics are likely alpha crystalline forms of imatinib.

“The generic has a different crystal type, so the product quality and treatment result will be totally different,” said Wendy Wang, head of communications for Novartis Oncology China.

The imatinib generics race is just warming up. According to CFDA’s database, as of July 16, there were 16 new applications for imatinib generics in 2013, including an imported drug application.

  Read More & Comment...

Utility Players

07/17/2013 07:22 AM |

For those of you following the recent CMS decision to deny coverage for contrast-enhanced PET scans ("Taking CMS to the Wood CED"), BioCentury’s Steve Usdin offers a timely and granular peek into the related world of laboratory-developed molecular diagnostics, detailing the cost, time and risk required to get these basic tools of personalized medicine onto the market -- and the decreasing the certainty that they will be covered. 

Some snippets:

The cost of demonstrating clinical utility, along with the lack of clear or consistent standards, is killing a business model that had made it possible for small companies to commercialize molecular diagnostics quickly and cheaply.

The fate of these laboratory-developed molecular diagnostics companies, and especially the conclusions investors draw about the viability of the space, could shape the future of personalized medicine.

Labs have been sparring with FDA for at least a decade over the agency’s attempts to regulate LDTs, and so far they’ve kept the regulators at bay. FDA Commissioner Margaret Hamburg opened the latest front at the American

Society of Clinical Oncology meeting in June, when she announced the agency plans to eliminate the regulatory distinction between LDTs and in vitro diagnostics marketed to multiple labs or physicians that have long been subject to premarket review.

The agency has developed a draft guidance that would “regulate all in vitro diagnostic tests in the same risk-based framework the agency currently uses, whether or not they are performed by a single laboratory.”

While FDA will find it difficult to use guidance documents or rules to impose clinical utility requirements on LDTs, payers have found a more prosaic tool for achieving the same goal: billing codes.

The full BioCentury article, “Coding for Utility,” can be found here.

 

  Read More & Comment...