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From the Pink Sheet ...
FDA is making the case for increased data-sharing and disclosure about drug development failures in the name of bolstering regulatory science.
In a speech to the Food and Drug Law Institute’s annual meeting on April 5, FDA Commissioner Margaret Hamburg said agency disclosure of reasons why a drug failed to win approval would strengthen the scientific underpinnings of drug development and regulatory review.
In addition, the agency is examining how it can mine its databases of submitted applications and approved products to help address scientific uncertainties in the development process.
Hamburg used the FDLI speech to link two of her key initiatives since joining the agency in May 2009 – strengthening regulatory science and increasing transparency of agency actions.
Despite the agency’s stance that increased data-sharing and disclosure would speed the drug development process, such concepts are sure to see pushback from pharmaceutical companies concerned about protecting proprietary information.
Spurring Innovation …
Hamburg’s speech to FDLI focused on the theme of innovation and what she said was FDA’s responsibility “to take advantage of our unique position” to help deliver new, ground-breaking medical products.
“Innovative products that are truly transformative create unique scientific and regulatory challenges, so we’re rolling up our sleeves, developing FDA’s regulatory science and innovation initiative strategy and doing everything that we can to rise to the challenges and to ensure that FDA is a consistently powerful catalyst for innovation,” Hamburg said.
“Moving forward, we’ll focus our efforts on several distinct yet inter-related areas of activity, each of which must be addressed if we are to make a meaningful difference in supporting innovation.”
The first area she touched on is regulatory reform, saying, “We’ll continue to work hard to streamline and modernize regulatory pathways and make them more predictable and transparent.” She cited several examples of FDA action in this regard, including its ongoing implementation of the “21st Century Review Process,” also known as good review management practices, and encouraging a quality-by-design approach to drug manufacturing.
“In each of these cases regulatory reform involved changing practices but also developing and applying better scientific understanding and tools to the review process, which brings me to the second area, strengthening science and reducing scientific uncertainty,” Hamburg said.
Hamburg unveiled her regulatory science platform in October. Among the initiative’s goals are modernizing product development; improving the speed, efficiency and predictability of the development, application review and manufacturing process; and using informatics to enhance health and drug safety
FDA’s fiscal 2012 budget request seeks $48.7 million in new funding for the program
Regulatory uncertainty is rooted both in scientific uncertainty and the failure to capitalize on existing knowledge, she said.
“At FDA, we have all of the data for every medical product ever submitted and approved in the U.S. There are huge opportunities to mine this information for the benefit of everybody to learn how to more effectively design drugs, to learn more about why products fail and how to better predict failure, and perhaps how to repurpose certain … drugs as we learn more about how to better assess subpopulations of responders.”
Developing new ways to share data and enhance communications with companies, without compromising trade secrets and other important commercial confidential information, is an important priority for FDA and should be for industry as well, Hamburg said. “This is part of what I mean by changing systems. We need to replace what is outmoded or not working with stronger, more effective patterns of practices.”
…Instead Of Waiting For Failure
During the question-and-answer session following her speech, Hamburg was asked how the concept of data-sharing would work “on a nuts and bolts basis” given industry concerns with such a proposal.
“This is an area that we’re obviously looking at carefully and cautiously and any decisions going forward would be done in partnership … with our key stakeholders,” she said.
She noted that agency scientists already have begun looking at data-mining opportunities with external partners, and the agency’s Transparency Initiative is examining some of the issues pertaining to disclosure.
FDA’s Transparency Task Force issued draft recommendations in May aimed at increasing public disclosure about agency actions. These included disclosing the existence and contents of “complete response” and “refuse to file” letters for NDAs and BLAs, as well as summary safety and effectiveness information for investigational applications or pending marketing applications if doing so would benefit public health
Many of the disclosure proposals drew strong objections from the Pharmaceutical Research and Manufacturers of America and the Biotechnology Industry Organization, which raised concerns about protecting trade secrets and the recommendations’ legality
However, Hamburg pointed to the benefits of disclosing information about why a drug was not approved.
“That can contain very, very important information to the R&D field more broadly,” she said, noting that there might be “multiple sponsors developing drugs following scientific pathways that, based on earlier work done, we know will fail. It’s not in the interest of those companies or the broader public good to just sit and watch them fail.”
Hamburg suggested that industry and individual companies would have to be on board with the disclosure concept. “A given company would have to be willing to say, ‘I understand there is a common good here … even though it might be demonstrating my dirty laundry just a little bit.’”
FDA is not alone among regulators in seeking to encourage such data-sharing and disclosure on drugs in development and clinical failures, she said.
“This is something that other regulatory authorities are also thinking about and working on as well because it’s an issue of really helping to build out the underlying science as we think about how can we make both the medical product development process as targeted and as effective and as efficient as possible, and how can we utilize the information that we have as regulators to support that process.”
Hamburg was asked whether FDA is discussing unilateral disclosure of information about drug development programs even if a sponsor objects. “It’s a discussion that we’re having, and I think it’s a partnership working with industry,” she said. “We need to move in directions that make sense, that will have value added, and where everyone understands the expectations and the opportunities.”
By Sue Sutter
Good feature in the April edition of Nature Biotechnology. Penned by Jeff Fox, the atrticle is titled, "Mixed Messages from Washington."
How unusual!
Good parts about FOBs and FDA funding as well as other excellent bits.
One snippet, "PDUFA negotiations provide an excellent opportunity to lay it on the line honestly and explain to Congress why FDA needs to be funded robustly. PDUFA, "gave industry better predictability and FDA more money, but it swerved off that path and promises were not kept. Industry now wants to get back to those promises."
Who said that? For the answer to that question and many others, see the complete article here.
A BILL
To protect all patients by prohibiting the use of data obtained from comparative effectiveness research to deny or delay coverage of items or services under Federal health care programs and to ensure that comparative effectiveness research accounts for advancements in personalized medicine and differences in patient treatment response.
Be it enacted by the Senate and House of Representatives of the United States of America in Congress assembled,
SECTION 1. SHORT TITLE.
This Act may be cited as the ‘Preserving Access to Targeted, Individualized, and Effective New Treatments and Services (PATIENTS) Act of 2011’ or the ‘PATIENTS Act of 2011’.
SEC. 2. PROHIBITION ON CERTAIN USES OF DATA OBTAINED FROM COMPARATIVE EFFECTIVENESS RESEARCH; ACCOUNTING FOR PERSONALIZED MEDICINE AND DIFFERENCES IN PATIENT TREATMENT RESPONSE.
(a) In General- Notwithstanding any other provision of law, the Secretary of Health and Human Services--
(1) shall not use data obtained from the conduct of comparative effectiveness research, including such research that is conducted or supported using funds appropriated under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5) or authorized or appropriated under the Patient Protection and Affordable Care Act (Public Law 111-148), to deny or delay coverage of an item or service under a Federal health care program (as defined in section 1128B(f) of the Social Security Act (42 U.S.C. 1320a-7b(f))); and
(2) shall ensure that comparative effectiveness research conducted or supported by the Federal Government accounts for factors contributing to differences in the treatment response and treatment preferences of patients, including patient-reported outcomes, genomics and personalized medicine, the unique needs of health disparity populations, and indirect patient benefits.
sun-sentinel.com/news/opinion/fl-nbcol-avastin-brochu-0407-20110407,0,5456672.column
South Florida Sun-Sentinel.com
Put Avastin, and the FDA, back on the fast track
Nicole Brochu
Sun Sentinel Columnist
April 7, 2011
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The FDA's announced intention to revoke Avastin's approval as treatment for late-stage breast cancer continues to inflame debate, with most commentary I've seen resoundingly against the government's plans. Here, a patient advocate provides some insight on the FDA's flawed process for fast-track approval of drugs. Give it a read and tell us your thoughts in the comment section below. — Nicole Brochu
By Robert Goldberg
At a time when the approval of new cancer drugs is declining, why is the FDA making it even harder to keep existing treatments on the market? When the FDA in December announced plans to revoke Avastin's designation as a breast cancer treatment, many Americans received their first exposure to the FDA's dysfunctional fast-track approval program. And it's clear the FDA decision and others like it are partly to blame for the fact that less than 5 percent of all cancer drugs in development make it to patients.
Since it was approved for treating advanced breast cancer in 2008, Avastin has helped improve the quality of life for many women suffering from the disease. By working with chemotherapy drug Taxol, Avastin can slow the growth of tumors — or even shrink them in certain patients.
Now the FDA has changed its mind about Avastin after a subsequent study — one required under the fast-track approval program — suggested it did not sufficiently prolong the average life expectancy of breast cancer patients. But extending average lifespan was not why Avastin was approved in the first place. Sometime between approving the drug and evaluating the follow-up study, the FDA moved the goalposts.
Such follow-up studies are both the heart and the Achilles heel of the fast-track approval program. In exchange for speedy approval of lifesaving cancer drugs, pharmaceutical companies must promise to conduct follow-up studies proving that the drugs can get the job done. Unfortunately, those studies have proven difficult to complete, with some taking more than six years, according to the FDA. Even when the studies are completed, the drug makers' only reward is sometimes the revocation of its approved status.
Why do these follow-up studies pose such a challenge for drug manufacturers? The FDA was wondering the same thing and grilled representatives from GlaxoSmithKline, Eli Lilly and Amgen about the delays at a February advisory committee meeting.
The drug companies offered a range of defenses. For drugs approved for rare forms of cancer, like GlaxoSmithKline's Bexxar, it can be tough to find enough patients to generate reliable results. Other trials can't go forward because by the time drug makers get around to doing them, the protocols have grown outdated — a point the FDA conceded.
The FDA is now making a show of how seriously it takes these studies. "These confirmatory trials are as important — if not more important — than the initial trials leading to the accelerated approval," FDA cancer chief Richard Pazdur told the assembled companies. But if the agency really wants to see them completed, it should support real-world studies to identify which patients respond best to specific drugs. And a good place to start would be to encourage the development of new medications with that focus.
As it stands now, the FDA's hurdles for cancer drugs are increasing. Avastin was approved for late-stage breast cancer more than two years ago because of its effects on tumor growth, which helped many patients live longer and more comfortably. But the new standard that the FDA used to evaluate the follow-up study last summer is called "overall median survival," which measures how long the average patient lives because of the drug.
Unfortunately, Avastin doesn't fare well under that standard because the bulk of its benefit falls on a key set of "super responders" who live significantly longer. For the average patient, however, Avastin only improves the quality of life rather than significantly extends it.
This would not be the first time a fast-tracked drug has been stripped of its designation because of a follow-up study. When AstraZeneca turned in follow-up data on lung cancer drug Iressa in 2005, the FDA pulled that approval as well, though the drug has gained new life from genetic screening. Four other drugs have met a similar fate. If the FDA allowed companies to keep drugs on the market while studying them — as they do with HIV drugs — everyone would have learned more faster.
Genentech is appealing the FDA's decision on Avastin, and concerned breast cancer patients have asked Congress to intervene. Many believe that the FDA was influenced by Avastin's high cost, even though the agency is only supposed to consider safety and efficacy. If the ruling is allowed to stand, a good drug will once again fall victim to bad policy, and countless women could miss out on months or even years of life gained from taking Avastin.
Drugs are granted fast-track approval to further study. If the FDA wants to see those studies completed quickly and competently, it needs to stop skewing the outcomes by changing the rules of research. Such behavior contributes to a decline in new cancer drugs being approved. We must reverse course. Correcting the Avastin decision is a good place to start.
Dr. Robert Goldberg is vice president of the Center for Medicine in the Public Interest. He is also author of "Tabloid Medicine: How the Internet is Being Used To Hijack Medical Science For Fear and Profit" (Kaplan, December 2010).
Copyright © 2011, South Florida Sun-Sentinel
According to the Daily Telegraph:
Cash-strapped health authorities are doubling the effective cost of medicines for some patients with long-term conditions. They are urging GPs to reduce the number of pills on a given prescription, which now cost £7.40 a time in England. In some cases the number of pills per prescription has halved.
While health authorities say the guidance is to help reduce the NHS bill for wasted medicines - estimated at up to £300 million a year - there is suspicion that health authorities are increasingly resorting to the measure for financial reasons.
Health care trusts have been asked to changed their guidance to GPs in order to get them to issue shorter prescriptions for some patients.
Our friend and colleague David Taylor, professor of pharmaceutical policy at the University of London, warned that shorter prescriptions for those who were "well established" on medications could actually increase costs because of higher dispensing fees.
He said: "You need a flexible approach and not a rigid rule."
David Stout, chief executive of the PCT Network (one of the largest health care trusts), emphasized the prescription rationing idea was to save money through cutting waste, rather than increasing prescription charge revenue.
Further, study after study demonstrates that the more frequently a patient has to refill a prescription, the more likely that patient is not to refill that prescription.
Non-compliance is a bad strategy for cost-containment.
Biocentury reports ...
Genentech, CDER submit joint statement on Avastin
Genentech Inc. and FDA's Center for Drug Evaluation and Research said in a joint statement they have been unable to agree on "the central questions that must be answered" for Commissioner Margaret Hamburg to render a decision about whether to withdraw metastatic breast cancer from the label of Avastin bevacizumab.
Instead of submitting a single joint list of facts in dispute, the parties submitted a partial list that includes whether actions by other regulatory authorities and data from studies outside the first-line setting are relevant. Each party now intends to submit a separate document summarizing what it considers to be the central questions to be presented and resolved. Genentech and CDER have until May 5 to submit their summaries.
Karen Midthun, who is the presiding officer for a hearing on the matter scheduled for June 28-29, had asked the Roche (SIX:ROG; OTCQX:RHHBY) unit and CDER to submit a joint statement outlining facts that are not in dispute and issues that are disputed.
The Association of the British Pharmaceutical Industry has selected a comms man, Stephen Whitehead, to be its next chief executive. Whitehead has spent the past few years working in corporate affairs at a U.K. financial services group. He was group communications director at Prudential PLC, between 2007 and 2010; before that he was group corporate affairs director at the U.K. bank, Barclays PLC. But Whitehead also has pharmaceutical industry experience - he spent 10 years at Glaxo PLC and Eli Lilly & Co. in corporate affairs, becoming European director of corporate affairs at Lilly before leaving the sector in 2003.
As the Pink Sheet reports, “The association's choice of a leader with public communications and lobbying experience is timely. Whitehead comes on board at a time of policy transition - perhaps more accurately, turmoil - for U.K. pharmaceutical companies. They are facing the replacement of a 50-year-old method of controlling their pricing and profits, the Pharmaceutical Pricing Regulation Scheme (PPRS), with a so far vaguely defined value-based pricing scheme.”
We are also pleased to report that our friend and colleague Richard Bergstrom has begun his new job as director general of the European Federation of the Pharmaceutical Industries and Associations EFPIA. (Richard was formerly director general of LIF, the trade association for the Swedish pharmaceutical industry.)
Is there are rhyme or reason to the FDA’s approach to safety?
On food dyes and ADHD there was no reason to revisit an issue that channels the same approach to causality the Andrew Wakefield, Jenny McCarthy and anti-vax crazies used. (And shame on the media for not referring to the European Food Safety Agency report trashing the Lancet article most reporters cited – in tandem with a real life story of a kid being cured of ADHD by going natural. As in: “In 2009, EFSA re-evaluated the safety of the six color additives used in the Southampton study and concluded that the available scientific evidence does not substantiate a link between the color additives and behavioral effects.)
Are reporters that biased or lazy that they can’t get beyond the he-said/she-said approach to reporting.
In any event, why, with this knowledge in hand did the FDA grant Center for Science in the Public Interest’s ( the same group that sued McDonald’s for offering Happy Meals to kids) citizen petition which was submitted in 2008?
Now the FDA has decided to allow pharmacists to compound a drug (Makema) developed by KV Pharmaceutical that significantly reduced the risk of certain preterm births in women who have had at least 1 prior preterm birth. Previously, the agent had only been available from pharmacies that had compounded the drug.” The FDA and ob-gyns had wanted a version of the injectable product that meet specific safety and efficacy standards. Since “Makena is a sterile injectable with a risk of contamination, greater assurance of safety is provided by an approved product. “
http://www.modernmedicine.com/modernmedicine/Clinical+News/FDA-wont-take-action-against-pharmacies-that-compo/ArticleStandard/Article/detail/714333?contextCategoryId=40157
After developing an FDA approved version of a drug that was in danger of becoming obsolete, KV promptly – and without warning – decided to charge $1500 for each dose. The company was rightly criticized for the sudden jump in price and did the right thing by cutting the retail price of the drug to $680 and offering the drug for free for a Medicaid price to a wide range of organizations.
The FDA decided to allow pharmacists to continue compounding even though KV developed the drug to put an end to the risk associated with compounding products. In case anyone didn’t know, the FDA is currently Investigating “bacteria that sickened 19 people at Alabama hospitals and may have killed nine and has turned up at compounding pharmacy in Alabama.
And then there were the pre-filled syringes of heparin and contaminiated compounded CF drugs.There are many more such examples.
To be sure the FDA does have the authority to ensure the availability of products and indirectly considers affordability. It did so when it kept generic asthma inhalers on the market for several years rather than forcing them off to comply with an EPA requirement to remove inhalers powered by CFCs.
But that was a well-considered and organized action. This is a reaction to the media hype. Indeed, the FDA even got involved in a little demagoguery when it cited the fact that the NIH had provided KV with support to conduct clinical trials as the reason to allow the compounding they sought to eliminate. Give that logic, maybe every drug developed in cooperation with the NIH or based on NIH research should be compounded. How about a nice home made batch of Herceptin or HIV drugs such as Prestiva and Norvir?
All of this is preceded by the FDA’s children’s cough medicine obsession, you know that deadly drug that is linked to 39 deaths over 20 years, most of them do to overdosing by parents?
The FDA is in a shambles because of it’s pursuit of a politically correct position instead of a science-based regulatory policy. It's already discourage the makers of cancer drugs from pursuing follow studies by shifting the Avastin endpoint to overall survival. Now, its piling on KV and permiting the type of compounding that KV's drug was supposed to eliminate in an effort to protect expectant mothers. This is the Precautionary Principle run amok.
“In the multitude of counsellors there is safety.”
-- Proverbs xi.14.
CDER’s Office of Surveillance and Epidemiology has been raised to the level of a a “super-office” to provide (at least in theory) greater management support to the unit’s growing staff and responsibilities.
As outlined by Super CDER Director Janet Woodcock, OSE will become a super-office that houses two new subordinate offices. According to Janet, “As OSE continues to build capacity and take on new responsibilities, and as the breadth, depth and volume of its work continue to increase, we need an organizational structure that provides adequate management support for these vital program areas.”
The changes will result in a new layer of management, in the form of the two new offices under OSE, which will have their own directors and deputy directors. The creation of a second epidemiology division, with its own director and deputy director, also will provide additional management support.
The Pink Sheet opines that, “The reorganization opens the door to a leadership change atop OSE.” Although OSE’s current director, Gerald Dal Pan, will serve as acting director of the new super-office, FDA will conduct a nationwide search for a permanent director.
“There is no safety in numbers – or in anything else.”
-- James Thurber
When it comes to the patient voice at the June 28-29 ODAC meeting on Avastin, silence most certainly does not imply consent
FDA's Karen Midthun, who will serve as presiding officer for the second ODAC hearing on the future of bevacizumab's (Avastin) breast cancer indication, has rejected Genentech’s request to allow members of the public to speak at the meeting.
This seems to be in direct contradiction to statements from CDER Office of New Drugs Director John Jenkins, who has gone on the public record that a crucial piece of risk/benefit assessment is the patient perspective.
"I think it's very important to understand the patients' perspective about how they value the benefits and how they are willing to accept the risk … A lot of us are basing these decisions in the abstract. We don't have the disease, we haven't achieved the benefit, and we do not actually have to weigh, personally, that benefit against the risk."
And further, "Regulators and others may not consider those benefits to be very important, but to the patients, they are extremely important and allowed them to go on about their lives.”
Dr. Midthun’s decision to ban patient comment is also contrary to the spirit of the 11/22/10 PDUFA negotiating session, where the FDA said that information about patients’ understanding of existing treatment tools is considered valuable, but is not consistently available during the review process.
The upcoming “Avastin Meeting” is, in all particulars, the perfect opportunity to take the “patient involvement” hypothesis out for a spin. Why is the agency afraid of what patient groups might say? Or does ODAC simply consider the patient voice not relevant? Advice mustn’t only be sought and considered when it supports your position.
After all, in the words of Dr. Jenkins, “We have to be aware of the societal expectations of how we interpret our standard and how we make our decisions.”
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.
