Latest Drugwonks' Blog
The Duke-Margolis Center working paper of off-label communications continues to provide forward motion on this urgent and feisty public health issue.
As BioCentury reports, PhRMA EVP and General Counsel Mit Spears said that while the Duke-Margolis Center paper does a good job of making the public health case for improving off-label communications policies, it “dances around” the single most important issue: how FDA defines the “truthful and non-misleading” standard the courts have set for corporate free speech.
“I don’t think you can resolve the issue without resolving the question of what constitutes truthful and non-misleading information,” Spears said. “That’s up to FDA or the courts to decide, and we think it is much better if it is FDA.”
He told BioCentury there is a danger that courts could back FDA into a corner, mandating communications policies that comply with the First Amendment to the U.S. Constitution, but that don’t take all of the nuances of public health into consideration.
Spears and PhRMA did not participate in the Duke-Margolis Center working group.
Speaking as a member of the Duke-Margolis working group, I could not agree more. As the BioCentury article reports, Speaking at the Duke-Margolis Center meeting, Peter Pitts, president of the Center for Medicine in the Public Interest, also warned that the courts or Congress could take the off-label policy debate in directions that could be bad for public health. “Unless FDA steps up to the plate to lead this conversation, but also looks to outside advisors to help it formulate its viewpoints, we are all going to be sucked into a very unpleasant vortex,” he said.
The complete BioCentury article, “Off-Label Options,” can be found here.
As BioCentury reports, PhRMA EVP and General Counsel Mit Spears said that while the Duke-Margolis Center paper does a good job of making the public health case for improving off-label communications policies, it “dances around” the single most important issue: how FDA defines the “truthful and non-misleading” standard the courts have set for corporate free speech.
“I don’t think you can resolve the issue without resolving the question of what constitutes truthful and non-misleading information,” Spears said. “That’s up to FDA or the courts to decide, and we think it is much better if it is FDA.”
He told BioCentury there is a danger that courts could back FDA into a corner, mandating communications policies that comply with the First Amendment to the U.S. Constitution, but that don’t take all of the nuances of public health into consideration.
Spears and PhRMA did not participate in the Duke-Margolis Center working group.
Speaking as a member of the Duke-Margolis working group, I could not agree more. As the BioCentury article reports, Speaking at the Duke-Margolis Center meeting, Peter Pitts, president of the Center for Medicine in the Public Interest, also warned that the courts or Congress could take the off-label policy debate in directions that could be bad for public health. “Unless FDA steps up to the plate to lead this conversation, but also looks to outside advisors to help it formulate its viewpoints, we are all going to be sucked into a very unpleasant vortex,” he said.
The complete BioCentury article, “Off-Label Options,” can be found here.
Today is Rare Disease Day. You probably missed the media coverage because there was none.
That will make Steve Pearson, the founder of the Institute for Clinical and Economic Review(www.ICER.org) – the so-called drug pricing watchdog – very happy.
That’s because Dr. Pearson believes that public awareness of rare diseases leads us to invest in more and more treatments for even more rare diseases that – in his opinion – will make health care spending ‘unsustainable.’
Or has he put it in an article entitled, “Which Orphans Will Find a Home? The Rule of Rescue in Resource Allocation for Rare Diseases,” there is no apparent obligation to rescue identifiable
rare disease patients based on a duty of rescue within personal morality.” Rather, he claims that while the impulse to save people with rare diseases is appealing, it is more ethical to restrain that policy because it forces us to spend more money on health care at a time of “permanent” resource scarcity.
To put it bluntly, Pearson believes groups like ICER can use evidence-based policies to decide who shall live and die, who shall suffer and who shall thrive.
Let’s set aside the specious assertion that we are running out of money to spend on health care. Like many Malthusians, the underlying assumption shaping Pearson’s and ICER’s mission is the believe that there is a moral imperative to spend less on health care. And Pearson, like his Club of Rome predecessors, is gripped by the belief that we can’t take care of all these sick, disabled people at any price otherwise we will have no money for anything else!
Here is Pearson with his pessimism in full flower:
“Increasing numbers of expensive orphan drugs are expected to come to market. In addition,
advances in pharmacogenetics will soon be able to separate many common diseases, such as hypertension, arthritis, cancer, and diabetes, into numerous small and distinct subpopulations of patients with specific genetic profiles. This movement toward “personalized medicine” will
produce increasing numbers of drugs that have been developed to treat small, identifiable patient groups.
Instead of a new blockbuster drug to treat millions with hypertension, new targeted therapies will treat only those few thousand with a particular genetic makeup. As the eligible patient
populations decrease in size, the arguments for accepting higher prices per treatment will turn manageable overall costs into unsustainable ones. As the eligible patient populations decrease in size, the arguments for accepting higher prices per treatment will turn manageable
overall costs into unsustainable ones.”
If everyone has a rare disease, there will be fewer people with a one size fits all diagnosis. So the number of people with an illness will not increase (holding population growth constant.) That mathematical fact eludes Pearson who insists that all these new orphan drugs will crowd out spending for other health care services.
Similarly, claims of budgetary Armageddon have been overhyped by Pearson. Between 2007 and 2014,orphan drugs have increased as a percentage of spending on drugs (from about 2 percent to 4 percent in Europe and 5 percent to 8 percent in the United States ) even as the percentage spent on drugs has remained the same.
What about the impact of the ICER like restrictions Pearson wants to impose? Indeed, “orphan drugs currently have more coverage restrictions than non-orphan drugs in the United States, United Kingdom, and Netherlands.” And the United States is less restrictive than other countries.
The rationing of orphan drugs does increase suffering and cost lives. Frank Lichtenberg concludes that between 1999-2007, new orphan drug approvals reduced life years lost to rare disease by 4.2 percent a year. (Without these new drugs, the number of deaths would have climbed by about 1 percent a year)
In France, which took longer to pay for orphan drugs and paid for fewer relative to the US, the number of deaths declined by 1.8 percent.
This loss of life is, according to Pearson, the price we have to pay for avoiding scarcity.
And he believes that a “bright line between what constitutes a fair claim on health benefits and what does not will be difficult to draw.”
Indeed, ICER sets the cut off point for the rationing required to avoid ‘scarcity.’ It has determined exact numbers of people who will be denied access to a growing array of new medicines.
The media has hailed ICER’s effort to set drug prices. But these limits are determined by how valuable ICER thinks a new drug is and by the amount ICER believes should be spent on each new drug a year. This has led ICER to recommend limits on the use of new medicines – even when they are price at levels that would make their development economically impossible – that ensures some people will suffer and die in order to stick to an arbitrary budget threshold. Indeed, ICER assumes that a new drug – even a cure – is of lower value to society if it increases cost beyond a certain limit.
Indeed, Pearson’s bright line is drawn based on the number of people that can be treated and little more. He says that paying $200K for a rare orphan drug is reasonable if it only helps a small number of patients. But he concludes that people with the toughest cancers to treat, for whom a small average survival benefit is a breakthrough, are not worth treating. He claims lung cancer patients shouldn’t stir our compassion because our feelings are simply a response to a patient led PR campaign. Pearson states: “Although nonsmall cell lung cancer is technically a rare disease, 60,000 patients are diagnosed with the illness each year in the United States. The treatment costs for each individual patient average approximately $80,000, which translates into an expenditure of $4.8 billion dollars per year. “
Pearson – and ICER – deliberately ignore the fact that average overall survival means very little at time when we can match people to combinations of treatments based on our understanding of how tumors thrive and progress. But even if they did incorporate it, the cumulative spending on lung cancer patients -- $4.8 billion – is about $3.9 billion more than ICER wants to spend on each new drug. New immunotherapy drugs double the percent of patients living a year or more with lung cancer. To Pearson, that’s bad news indeed.
He, like so many social engineers before him, have assumed that keeping more people alive longer will hurt society as a whole. But incremental and cumulative advances in medicine, as they are diffused and adopted, leads to greater gains in well-being and economic growth.
It is precisely our moral sense to save lives in immediate danger and at any expense that sustains humanity and economic progress. We need more orphan drugs because we gain when more of us enjoy life and live longer.
Pearson and his ICER are a threat to that prosperity and the remarkable advances in medicine that Rare Disease Day celebrates. Do we really want to allow someone who belittles such acts of awareness to determine who gets what medicines at what price??
What hypocrisy.
CVS’ ballyhoo that they “reduced the rate of drug spending” in 2015 is barely half the story. And as my grandmother used to say, “A half-truth is a whole lie.”
CVS, which manages drug benefit plans for more than 75 million Americans, kept costs down in 2015 by negotiating discounts from big manufacturers and carefully managing its list of covered drugs – and by denying patients the medicines prescribed by their physicians.
Yes, they decreased RX expenses but they haven’t any clue what happened to overall healthcare costs, out of pocket costs and, more importantly, patient outcomes.
In a nutshell, CVS removed some drugs from formularies and limited access to others – and asthmatics are in the emergency room. That’s not a public health victory.
CVS’ ballyhoo that they “reduced the rate of drug spending” in 2015 is barely half the story. And as my grandmother used to say, “A half-truth is a whole lie.”
CVS, which manages drug benefit plans for more than 75 million Americans, kept costs down in 2015 by negotiating discounts from big manufacturers and carefully managing its list of covered drugs – and by denying patients the medicines prescribed by their physicians.
Yes, they decreased RX expenses but they haven’t any clue what happened to overall healthcare costs, out of pocket costs and, more importantly, patient outcomes.
In a nutshell, CVS removed some drugs from formularies and limited access to others – and asthmatics are in the emergency room. That’s not a public health victory.
The good news is that Rob Califf has been confirmed as FDA Commissioner. Dr. Califf is the right man in the right place at the right time. Better late than never.
At a crucial moment in American (indeed global) healthcare, he brings a vision for FDA as an innovation accelerator, steward of post-market safety, guarantor of quality, and first among equals when it comes to leading the agency’s intramural partnerships on a plethora of issues with its many constituencies. Perhaps most importantly, is Califf's role as agenda-setter and cheer leader at an agency comprised of highly educated and dedicated (and career) public servants.
The past is prologue.
At a crucial moment in American (indeed global) healthcare, he brings a vision for FDA as an innovation accelerator, steward of post-market safety, guarantor of quality, and first among equals when it comes to leading the agency’s intramural partnerships on a plethora of issues with its many constituencies. Perhaps most importantly, is Califf's role as agenda-setter and cheer leader at an agency comprised of highly educated and dedicated (and career) public servants.
The past is prologue.
Jimmy Carter's successful battle with advanced melanoma was achieved because he was able to use newest, most effective drug available rather than being forced to fail on other treatments by health plans and PBMs.
Now policymakers want to make sure you don't have to be an ex-President to get the best treatment immediately:
Georgia Bill Inspired by Jimmy Carter's Cancer Treatment
Georgia lawmakers have approved a bill inspired by former President Jimmy Carter's cancer treatment.
The bill prevents insurance companies from limiting coverage of drugs for stage 4 cancer patients.
Carter, now 91, announced in August that he had been diagnosed with skin cancer that had spread to his brain and would begin receiving doses of Keytruda. The newly approved drug helps his immune system seek out cancer cells appearing in his body.
Carter said in December that a scan of his brain detected no sign of cancer cells. He has continued treatment.
Republican Rep. Mike Cheokas from Americus is the bill's sponsor. Cheokas said no one facing cancer that has spread should have medical treatment options limited by insurance providers.
The bill now goes to the state Senate for review.
In introducing the bill, Representative Cheokas said something that should be a campaign slogan nation-wide: "Cancer is a non-partisan issue. It affects young and old, black and white, rich or poor; It really doesn't matter."
Now policymakers want to make sure you don't have to be an ex-President to get the best treatment immediately:
Georgia Bill Inspired by Jimmy Carter's Cancer Treatment
Georgia lawmakers have approved a bill inspired by former President Jimmy Carter's cancer treatment.
The bill prevents insurance companies from limiting coverage of drugs for stage 4 cancer patients.
Carter, now 91, announced in August that he had been diagnosed with skin cancer that had spread to his brain and would begin receiving doses of Keytruda. The newly approved drug helps his immune system seek out cancer cells appearing in his body.
Carter said in December that a scan of his brain detected no sign of cancer cells. He has continued treatment.
Republican Rep. Mike Cheokas from Americus is the bill's sponsor. Cheokas said no one facing cancer that has spread should have medical treatment options limited by insurance providers.
The bill now goes to the state Senate for review.
In introducing the bill, Representative Cheokas said something that should be a campaign slogan nation-wide: "Cancer is a non-partisan issue. It affects young and old, black and white, rich or poor; It really doesn't matter."
STAT, the new online health publication, cheerily reports that CVS Caremark, the nation’s second-largest pharmacy benefits manager, was able to achieve the long anticipated goal of cutting the rise in drug spending. STAT links to a good article by Matt Herper that notes CVS was able to blunt these hikes by fine-tuning its list of covered drugs and adjusting patient co-pays, among other tactics, according to Troy Brennan, CVS’ chief medical officer and executive vice president. The result: Its clients' spending on prescription drugs rose just 5 percent last year, compared with nearly 11.8 percent in 2014. The report comes at a time of growing anger over rising drug prices —and also, growing questions about whether pharmacy benefits managers (PBMs) restrict patients' choice of drugs too much in the name of holding down costs.
But the real heroes in the ‘battle’ to reduce what are always referred to as skyrocketing drug costs are people like Nicole who are denied access to new medicines in order to pad the profits of CVS and other PBMs:
Nichole, a 25-year-old living with Hepatitis C, was desperate when she reached out to WBZ-TV.
“A week ago, I didn’t feel any hope,” she told the I-Team.
She had been struggling with the disease since she was abducted four years ago. The fatigue and jaundice, plus the stigma made it hard to get on with her life.
Making matters worse, the man who victimized her had received a life-saving cure in prison.
Nichole was left only with multiple denial letters from her insurance company, Tufts Health Plan.
“Aside from the physical, emotionally, this has been horrible,” she told WBZ in January.
Nichole’s doctor prescribed it saying she was a perfect candidate. It would help rid her of the disease and move on. However, a full treatment of Harvoni is priced at a whopping $84,000. That’s $1,000 per pill. Tufts Health Plan denied Nichole coverage of the drug, saying she isn’t sick enough yet. “The insurance company wants me to be in Stage 3 liver scarring,” she said.
Let the record show that this denial comes from CVS, the hero of drug pricing critics. And the rationale for rationing Nicole is courtesy of our friends at the Institute for Clinical and Economic Review. These drug price watchdogs, as their acolytes in the media has hailed ICER, has recommended that HCV patients like Nicole be denied cures until there “is some evidence of liver fibrosis.” More on this media anointed (as well as health plan and Enron billionaire funded) arbiter of price and the value of a human life in a future post.
And don’t forget that CVS has an exclusive deal with Gliead to make it the only HCV drug on their formulary. But even then, you have to fail first or get liver damage to try another drug.
Nicole is one of the lucky ones. According to Camilla Graham, MD, assistant professor of medicine at Beth Israel Deaconess Medical Center in Boston. Every single Viekira Pak scrip she has written for her Medicaid patients has been denied. “Things aren't going so well, and Massachusetts, I will say, has the best access of any state. Our Medicaid doesn't have ridiculous restrictions,” she says. “I'm calling them restrictions, but it's really rationing. We're seeing rationing of care for hepatitis C like I've never seen in U.S. medicine.”
CVS’ chief medical officer, Troyen Brennan, said that without Sovaldi being introduced, the 11.8% growth might have been about 10%, and that this year’s spending growth would have remained at about 5%.
But wasn’t Solvadi going to increase premiums by 30 percent? Brennan co-authored a piece in JAMA in which he asserted. “ The simple math is that treatment of patients with HCV could add $200 to $300 per year to every insured American's health insurance premium for each of the next 5 years,"
That’s BS obviously. Even worse, it was BS used to justify rationing drugs and cutting exclusive deals with drug companies so that sick patients would have to beg for cure.
Meanwhile, the “fine-tuning” as Matt Herper happily describes is more like a blitzkrieg against access. As Adam Fein dryly notes:
Express Scripts has 66 products on its 2015 formulary exclusion list, compared with 48 in 2014. CVS Caremark’s 2015 list has 95 products, including 72 carryovers from the 2014 edition. Nostalgic readers will recall that CVS Caremark removed a mere 34 drugs from its 2012 standard national formulary. I guess there ain't no valley low enough, either.
Adam’s right. CVS and other PBMs haven’t reach their low point in limiting access, cutting deals and using ICER as a price fixing front in order to maximize the spread between the net cost of a drug (often up to 40 percent of average wholesale price) and how much they force patients to pay out of pocket for medicines that are right for them.
As Stacy Trooskin, MD, PhD, assistant professor in the division of infectious diseases and HIV medicine at Drexel University College of Medicine in Philadelphia points out: “I get a little bit concerned when we have exclusivity deals and none of these price cuts that the payer is receiving from the pharmaceutical company translate to ease of access.”
The decline in drug costs is a result of the increased success of PBMs extracting rebates and denying access. A Credit Suisse analyst report found that: “For 2014, our 20 company universe has shown net US drug sales of $202bn and reported total rebates of $98bn. We conclude that in 2014 US rebates rose 24% against just a 7% increase in net sales, reflecting continued formulary pressures. “
Which means that 2015 was a great year for PBMs because it was worse for patients.
But the real heroes in the ‘battle’ to reduce what are always referred to as skyrocketing drug costs are people like Nicole who are denied access to new medicines in order to pad the profits of CVS and other PBMs:
Nichole, a 25-year-old living with Hepatitis C, was desperate when she reached out to WBZ-TV.
“A week ago, I didn’t feel any hope,” she told the I-Team.
She had been struggling with the disease since she was abducted four years ago. The fatigue and jaundice, plus the stigma made it hard to get on with her life.
Making matters worse, the man who victimized her had received a life-saving cure in prison.
Nichole was left only with multiple denial letters from her insurance company, Tufts Health Plan.
“Aside from the physical, emotionally, this has been horrible,” she told WBZ in January.
Nichole’s doctor prescribed it saying she was a perfect candidate. It would help rid her of the disease and move on. However, a full treatment of Harvoni is priced at a whopping $84,000. That’s $1,000 per pill. Tufts Health Plan denied Nichole coverage of the drug, saying she isn’t sick enough yet. “The insurance company wants me to be in Stage 3 liver scarring,” she said.
Let the record show that this denial comes from CVS, the hero of drug pricing critics. And the rationale for rationing Nicole is courtesy of our friends at the Institute for Clinical and Economic Review. These drug price watchdogs, as their acolytes in the media has hailed ICER, has recommended that HCV patients like Nicole be denied cures until there “is some evidence of liver fibrosis.” More on this media anointed (as well as health plan and Enron billionaire funded) arbiter of price and the value of a human life in a future post.
And don’t forget that CVS has an exclusive deal with Gliead to make it the only HCV drug on their formulary. But even then, you have to fail first or get liver damage to try another drug.
Nicole is one of the lucky ones. According to Camilla Graham, MD, assistant professor of medicine at Beth Israel Deaconess Medical Center in Boston. Every single Viekira Pak scrip she has written for her Medicaid patients has been denied. “Things aren't going so well, and Massachusetts, I will say, has the best access of any state. Our Medicaid doesn't have ridiculous restrictions,” she says. “I'm calling them restrictions, but it's really rationing. We're seeing rationing of care for hepatitis C like I've never seen in U.S. medicine.”
CVS’ chief medical officer, Troyen Brennan, said that without Sovaldi being introduced, the 11.8% growth might have been about 10%, and that this year’s spending growth would have remained at about 5%.
But wasn’t Solvadi going to increase premiums by 30 percent? Brennan co-authored a piece in JAMA in which he asserted. “ The simple math is that treatment of patients with HCV could add $200 to $300 per year to every insured American's health insurance premium for each of the next 5 years,"
That’s BS obviously. Even worse, it was BS used to justify rationing drugs and cutting exclusive deals with drug companies so that sick patients would have to beg for cure.
Meanwhile, the “fine-tuning” as Matt Herper happily describes is more like a blitzkrieg against access. As Adam Fein dryly notes:
Express Scripts has 66 products on its 2015 formulary exclusion list, compared with 48 in 2014. CVS Caremark’s 2015 list has 95 products, including 72 carryovers from the 2014 edition. Nostalgic readers will recall that CVS Caremark removed a mere 34 drugs from its 2012 standard national formulary. I guess there ain't no valley low enough, either.
Adam’s right. CVS and other PBMs haven’t reach their low point in limiting access, cutting deals and using ICER as a price fixing front in order to maximize the spread between the net cost of a drug (often up to 40 percent of average wholesale price) and how much they force patients to pay out of pocket for medicines that are right for them.
As Stacy Trooskin, MD, PhD, assistant professor in the division of infectious diseases and HIV medicine at Drexel University College of Medicine in Philadelphia points out: “I get a little bit concerned when we have exclusivity deals and none of these price cuts that the payer is receiving from the pharmaceutical company translate to ease of access.”
The decline in drug costs is a result of the increased success of PBMs extracting rebates and denying access. A Credit Suisse analyst report found that: “For 2014, our 20 company universe has shown net US drug sales of $202bn and reported total rebates of $98bn. We conclude that in 2014 US rebates rose 24% against just a 7% increase in net sales, reflecting continued formulary pressures. “
Which means that 2015 was a great year for PBMs because it was worse for patients.
Per a new report in BioCentury, rather than pave new ground, industry and FDA have agreed PDUFA VI will be more about fixing potholes that have been persistent impediments to modernizing the agency’s oversight and review of drugs, and providing more resources to promote the expansion of projects started under PDUFA V.
The most important outcomes are steps that are intended to improve FDA’s ability to recruit, hire and retain scientific staff, measures to improve the agency’s financial transparency and accountability, and extensions of ongoing efforts to integrate patient perspectives and real-world data into regulatory decision making.
Completion of the goals letter, expected in March, and review by HHS and the White House over the summer, will mark the end of the first phase of the PDUFA reauthorization process. But it only will launch the start of the much more arduous portion of the PDUFA reauthorization journey: congressional approval.
I. Fixing HR
FDA’s ability to meet user fee review goals, and to go beyond them by implementing new regulatory ideas and proactively supporting product development, depends almost entirely on its ability to recruit, retain and develop talented and dedicated staff.
At the start of PDUFA VI negotiations, PhRMA and BIO told FDA that industry would not support increases in user fees to hire new staff unless CDER demonstrated that it had put procedures in place that would fill staffing holes and provide confidence it could hire to fill new positions funded by PDUFA VI. According to industry negotiators, CDER and FDA have met the challenge, in part by taking some steps that are common in the private sector, such as hiring external head hunters.
Unlike previous user fee agreements, which paid for FTEs even if they were never hired, the agency will only receive the additional money if it meets recruitment and retention goals. FDA has also agreed to hire an external organization to assess and continuously evaluate its hiring and retention efforts.
Other nuts-and-bolts activities covered in PDUFA VI include improving the reliability of the electronic filing process for new drug applications, steps to improve the management of meetings between FDA and sponsors, and revamping a formula that is used to increase user fee payments based on estimated workload.
II. Breakthroughs and Biomarkers
Some of the new hires will work on improving FDA’s review of products that combine drugs and devices, and on the breakthrough therapies program. The breakthrough process is resource-intensive, and the largest allocation of new staff in PDUFA VI, about 60 employees, will be dedicated to breakthrough reviews. PDUFA VI will also include additional money and mandates for FDA to review drug development tools, including surrogate endpoints, biomarkers and patient-reported outcomes (PROs).
Alas. industry dropped attempts to establish review time goals for biomarker qualification.
Advancing FDA’s patient-focused drug development (PFDD) initiative is another priority for patient groups as well as for industry and FDA. FDA has already started expanding PFDD by encouraging patient groups to hold their own meetings modeled on meetings the agency has held. PDUFA VI will include a series of guidance documents that are intended to lead to PFDD version 2.0, which could include establishing standards for conducting and analyzing patient-preference research, and taking steps to formally integrate patient preferences into regulatory decisions.
FDA created structured benefit-risk frameworks during PDUFA V, and will expand their use in PDUFA VI.
Advancing the use of real-world evidence to make regulatory decisions will be another major emphasis of PDUFA VI. This will include enhancing the Sentinel Initiative, a system that allows investigators to monitor and query electronic medical records, health claims databases and other sources. Projects under consideration for Sentinel include monitoring the safety of biosimilars, and broadening its focus from safety to efficacy.
Biopharmaceutical companies are looking to PDUFA VI to open legal avenues to communicating with payers and possibly other parties about real-world data on off-label uses of approved drugs.
Finalization of the draft PDUFA VI goals letter will set in motion a series of reviews by HHS and the White House Office of Management and Budget that are slated to be completed by September. Following publication of the draft agreement in September, and a final public meeting in October or November, the deal should be formally submitted to Congress in mid-January.
PDUFA VI AT A GLANCE
* Improve FDA recruitment, hiring, retention: Implement HR improvements, hire outside HR contractors, contract for external analysis and monitoring of progress
* Funding for about 200 additional full-time employees (FTEs): Funding contingent on FDA meeting recruitment, retention goals
* Increased funding for breakthrough reviews: Largest portion of new FTEs
* Modification of the “workload adjustor” formula used to increase user fee payments based on anticipated submissions: Annual user fee increases expected to be smaller; FDA to gain more predictable funding
* Patient-focused drug development 2.0: Issue a series of new guidance documents on patient-focused drug development
* Research on the integration of real-world evidence into product reviews: Expand Sentinel Initiative, a system for postmarket monitoring and querying of electronic health records, insurance claims and other records to track medical product safety; Implement other efforts to use real-world evidence to study and communicate about safety and efficacy
* Increased funding for review of drug development tools: Add resources to qualify surrogate endpoints, biomarkers, patient-reported outcomes; Expand use of benefit-risk framework to guide drug development activities; Enhance FDA capacity to analyze innovative clinical trial designs
* Increased transparency regarding spending PDUFA funds
* Information technology improvements: Increase reliability of the electronic submissions system, upgrade CDER's IT system
The most important outcomes are steps that are intended to improve FDA’s ability to recruit, hire and retain scientific staff, measures to improve the agency’s financial transparency and accountability, and extensions of ongoing efforts to integrate patient perspectives and real-world data into regulatory decision making.
Completion of the goals letter, expected in March, and review by HHS and the White House over the summer, will mark the end of the first phase of the PDUFA reauthorization process. But it only will launch the start of the much more arduous portion of the PDUFA reauthorization journey: congressional approval.
I. Fixing HR
FDA’s ability to meet user fee review goals, and to go beyond them by implementing new regulatory ideas and proactively supporting product development, depends almost entirely on its ability to recruit, retain and develop talented and dedicated staff.
At the start of PDUFA VI negotiations, PhRMA and BIO told FDA that industry would not support increases in user fees to hire new staff unless CDER demonstrated that it had put procedures in place that would fill staffing holes and provide confidence it could hire to fill new positions funded by PDUFA VI. According to industry negotiators, CDER and FDA have met the challenge, in part by taking some steps that are common in the private sector, such as hiring external head hunters.
Unlike previous user fee agreements, which paid for FTEs even if they were never hired, the agency will only receive the additional money if it meets recruitment and retention goals. FDA has also agreed to hire an external organization to assess and continuously evaluate its hiring and retention efforts.
Other nuts-and-bolts activities covered in PDUFA VI include improving the reliability of the electronic filing process for new drug applications, steps to improve the management of meetings between FDA and sponsors, and revamping a formula that is used to increase user fee payments based on estimated workload.
II. Breakthroughs and Biomarkers
Some of the new hires will work on improving FDA’s review of products that combine drugs and devices, and on the breakthrough therapies program. The breakthrough process is resource-intensive, and the largest allocation of new staff in PDUFA VI, about 60 employees, will be dedicated to breakthrough reviews. PDUFA VI will also include additional money and mandates for FDA to review drug development tools, including surrogate endpoints, biomarkers and patient-reported outcomes (PROs).
Alas. industry dropped attempts to establish review time goals for biomarker qualification.
Advancing FDA’s patient-focused drug development (PFDD) initiative is another priority for patient groups as well as for industry and FDA. FDA has already started expanding PFDD by encouraging patient groups to hold their own meetings modeled on meetings the agency has held. PDUFA VI will include a series of guidance documents that are intended to lead to PFDD version 2.0, which could include establishing standards for conducting and analyzing patient-preference research, and taking steps to formally integrate patient preferences into regulatory decisions.
FDA created structured benefit-risk frameworks during PDUFA V, and will expand their use in PDUFA VI.
Advancing the use of real-world evidence to make regulatory decisions will be another major emphasis of PDUFA VI. This will include enhancing the Sentinel Initiative, a system that allows investigators to monitor and query electronic medical records, health claims databases and other sources. Projects under consideration for Sentinel include monitoring the safety of biosimilars, and broadening its focus from safety to efficacy.
Biopharmaceutical companies are looking to PDUFA VI to open legal avenues to communicating with payers and possibly other parties about real-world data on off-label uses of approved drugs.
Finalization of the draft PDUFA VI goals letter will set in motion a series of reviews by HHS and the White House Office of Management and Budget that are slated to be completed by September. Following publication of the draft agreement in September, and a final public meeting in October or November, the deal should be formally submitted to Congress in mid-January.
PDUFA VI AT A GLANCE
* Improve FDA recruitment, hiring, retention: Implement HR improvements, hire outside HR contractors, contract for external analysis and monitoring of progress
* Funding for about 200 additional full-time employees (FTEs): Funding contingent on FDA meeting recruitment, retention goals
* Increased funding for breakthrough reviews: Largest portion of new FTEs
* Modification of the “workload adjustor” formula used to increase user fee payments based on anticipated submissions: Annual user fee increases expected to be smaller; FDA to gain more predictable funding
* Patient-focused drug development 2.0: Issue a series of new guidance documents on patient-focused drug development
* Research on the integration of real-world evidence into product reviews: Expand Sentinel Initiative, a system for postmarket monitoring and querying of electronic health records, insurance claims and other records to track medical product safety; Implement other efforts to use real-world evidence to study and communicate about safety and efficacy
* Increased funding for review of drug development tools: Add resources to qualify surrogate endpoints, biomarkers, patient-reported outcomes; Expand use of benefit-risk framework to guide drug development activities; Enhance FDA capacity to analyze innovative clinical trial designs
* Increased transparency regarding spending PDUFA funds
* Information technology improvements: Increase reliability of the electronic submissions system, upgrade CDER's IT system
Yesterday the new Duke-Margolis Center for Health Policy (headed by Mark McClellan), held a conference titled, “Off Label Communication in 2016: Meeting Information Needs through New Policy Options.”
Those new options are detailed in an important new paper:
Policy Options for Off-Label Communication: Supporting Better Information, Better Evidence, and Better Care
I am honored to be one of the co-authors and to have had the opportunity to speak at the event.
Just about every speaker pointed to the need for FDA leadership – though bold action and … clarity.
This is urgent for many reasons: different federal agencies (FDA, FTC, DOJ) with different views on pathways and jurisdiction, and the extreme danger of allowing federal judges dictate regulatory policy. If existing policy has evolved to protect the public from snake oil, the recent Amarin decision is precarious precedent for communications about fish oil – and beyond.
The paper lays out what we refer to as Guiding Principles for Lasting Solutions. They are:
Promote well-informed clinical decision-making to improve public health.
Support FDA’s central role in reviewing, approving, and enforcing efficacy claims.
Reduce inconsistencies across agencies’ enforcement decision-making.
Avoid continued cycles of litigation through greater policy clarity.
Promote more evidence development and data submission to FDA.
Nature abhors a vacuum. All of the participants in the conference and all the authors of the white paper were in complete agreement that, absent strong and forward-looking FDA leadership, the off-label debate will result in public health chaos.
And, as many management gurus have written, one of the key tenets of successful leadership is the ability to delegate in order to get things done.
To that end, one of the more contentious policy recommendations made in the paper is for the FDA to pursue a strategy that embraces third party sanctioned communication.
This alternative, which did not have universal support within our working group, involves a more intramural approach based on the FDA’s partnering with an external entity charged with accrediting certain types of communication.
This organization could focus its efforts on reviewing not an NDA, but an NDI – New Drug/Device Information, consisting of a sponsor’s evidence and associated communications about off-label use, and then potentially approve them for broader distribution.
An NDI review could be given within a rank, score, or grade system that confers greater weight to better evidence, and could be given contingent upon continued evidence generation and resubmission to the clearing body.
For example, an off-label communication may be approved and given an initial grade or rating that sunsets within a specified number of years barring updated submission of relevant evidence. Continued off-label communication at the current evidentiary grade and after the specified date would then be subject to additional evidence development by the sponsor.
The proposed reviewing body would operate outside of FDA but with FDA participation. To avoid First Amendment and other legal concerns, the body’s conclusions could not bind the FDA or otherwise hinder FDA’s ability to pursue enforcement action. While the reviewing body would not provide certainty to the regulated community, its recommendations could offer useful guidance to drug manufacturers.
An approach that involves an outside reviewing body might enable FDA to advance a model that more clearly differentiates between types and levels of communication, without modifying the FDA-approved product labeling. For example, the reviewing body might treat communication around off-label use that has become standard of care in a different manner than more tailored or less-well-established evidence on an off-label indication or within a specific patient subpopulation. Such a system could potentially play a more directed and focused alternative or supplement to the current role of peer-reviewed communications.
Any such entity will need to have participation from the FDA, and potentially other relevant agencies and will need to include a robust peer-review capacity. Incentives in the form of more rapid and predictable review and action would need to be in place to encourage sponsors to develop evidence and submit communication materials.
The end goal would be a process that augments the FDA’s capacity to review a diversity of communication types reflective of rapidly emerging evidence -- but does not change FDA’s ability to pursue enforcement action.
Such a third-party approach has precedents. In Canada, for example, the Pharmaceutical Advertising Advisory Board (PAAB) serves as an independent preclearance review agency for assessing the accuracy and evidentiary basis for promotional information on prescription, non-prescription, biologic, and homeopathic products. The PAAB process works within the Canadian regulatory framework with Health Canada as an ex-officio member of board leadership, conferring “approval” of advertising materials through a logo incorporated on cleared materials.
There also may be useful lessons for a third-party off-label communication entity from the Center for Disease Control’s Advisory Committee on Immunization Practices (ACIP), which develops recommendations on how and when to use vaccines within the United States. With FDA as a party to committee deliberations, ACIP relies on the body of clinical evidence, sponsor labeling, and data sources to issue formal, non-binding advice for immunization best practices – including potential off-label uses of vaccines.
While these examples differ in important ways from a third-party review system for off-label materials, they illustrate features and feasibility concerns that would need to be addressed to ensure a trustworthy, collaborative, and science-based process.
Might the USP be a good home for such a program. They already have a time-tested intramural relationship with the FDA. It's a thought worth further discussion.
All this to say that off-label communication is now on the health policy front burner and the flame is on high. As Everett Dirksen used to say, “When I feel the heat, I see the light.”
Those new options are detailed in an important new paper:
Policy Options for Off-Label Communication: Supporting Better Information, Better Evidence, and Better Care
I am honored to be one of the co-authors and to have had the opportunity to speak at the event.
Just about every speaker pointed to the need for FDA leadership – though bold action and … clarity.
This is urgent for many reasons: different federal agencies (FDA, FTC, DOJ) with different views on pathways and jurisdiction, and the extreme danger of allowing federal judges dictate regulatory policy. If existing policy has evolved to protect the public from snake oil, the recent Amarin decision is precarious precedent for communications about fish oil – and beyond.
The paper lays out what we refer to as Guiding Principles for Lasting Solutions. They are:
Promote well-informed clinical decision-making to improve public health.
Support FDA’s central role in reviewing, approving, and enforcing efficacy claims.
Reduce inconsistencies across agencies’ enforcement decision-making.
Avoid continued cycles of litigation through greater policy clarity.
Promote more evidence development and data submission to FDA.
Nature abhors a vacuum. All of the participants in the conference and all the authors of the white paper were in complete agreement that, absent strong and forward-looking FDA leadership, the off-label debate will result in public health chaos.
And, as many management gurus have written, one of the key tenets of successful leadership is the ability to delegate in order to get things done.
To that end, one of the more contentious policy recommendations made in the paper is for the FDA to pursue a strategy that embraces third party sanctioned communication.
This alternative, which did not have universal support within our working group, involves a more intramural approach based on the FDA’s partnering with an external entity charged with accrediting certain types of communication.
This organization could focus its efforts on reviewing not an NDA, but an NDI – New Drug/Device Information, consisting of a sponsor’s evidence and associated communications about off-label use, and then potentially approve them for broader distribution.
An NDI review could be given within a rank, score, or grade system that confers greater weight to better evidence, and could be given contingent upon continued evidence generation and resubmission to the clearing body.
For example, an off-label communication may be approved and given an initial grade or rating that sunsets within a specified number of years barring updated submission of relevant evidence. Continued off-label communication at the current evidentiary grade and after the specified date would then be subject to additional evidence development by the sponsor.
The proposed reviewing body would operate outside of FDA but with FDA participation. To avoid First Amendment and other legal concerns, the body’s conclusions could not bind the FDA or otherwise hinder FDA’s ability to pursue enforcement action. While the reviewing body would not provide certainty to the regulated community, its recommendations could offer useful guidance to drug manufacturers.
An approach that involves an outside reviewing body might enable FDA to advance a model that more clearly differentiates between types and levels of communication, without modifying the FDA-approved product labeling. For example, the reviewing body might treat communication around off-label use that has become standard of care in a different manner than more tailored or less-well-established evidence on an off-label indication or within a specific patient subpopulation. Such a system could potentially play a more directed and focused alternative or supplement to the current role of peer-reviewed communications.
Any such entity will need to have participation from the FDA, and potentially other relevant agencies and will need to include a robust peer-review capacity. Incentives in the form of more rapid and predictable review and action would need to be in place to encourage sponsors to develop evidence and submit communication materials.
The end goal would be a process that augments the FDA’s capacity to review a diversity of communication types reflective of rapidly emerging evidence -- but does not change FDA’s ability to pursue enforcement action.
Such a third-party approach has precedents. In Canada, for example, the Pharmaceutical Advertising Advisory Board (PAAB) serves as an independent preclearance review agency for assessing the accuracy and evidentiary basis for promotional information on prescription, non-prescription, biologic, and homeopathic products. The PAAB process works within the Canadian regulatory framework with Health Canada as an ex-officio member of board leadership, conferring “approval” of advertising materials through a logo incorporated on cleared materials.
There also may be useful lessons for a third-party off-label communication entity from the Center for Disease Control’s Advisory Committee on Immunization Practices (ACIP), which develops recommendations on how and when to use vaccines within the United States. With FDA as a party to committee deliberations, ACIP relies on the body of clinical evidence, sponsor labeling, and data sources to issue formal, non-binding advice for immunization best practices – including potential off-label uses of vaccines.
While these examples differ in important ways from a third-party review system for off-label materials, they illustrate features and feasibility concerns that would need to be addressed to ensure a trustworthy, collaborative, and science-based process.
Might the USP be a good home for such a program. They already have a time-tested intramural relationship with the FDA. It's a thought worth further discussion.
All this to say that off-label communication is now on the health policy front burner and the flame is on high. As Everett Dirksen used to say, “When I feel the heat, I see the light.”
I am all for “transparency in drug pricing.” The question is transparency proponents have to answer is: why are they only focusing on how drug companies set their prices when the effective price consumers pay is set by PBMs, insurers and hospitals??
Take this story from Minneapolis.
A major company has rolled back the price of a potentially life-saving prescription drug after a KARE 11 News investigation.
But the decision has some people asking how often we’re being overcharged on other medicines.
Curt’s Story
It started with Curt Burshem.
Back in November he told us CVS Caremark had jacked up the price for a prescription drug a family member needed for a kidney disorder.
Curt Burshem discovered that CVS was overcharging him on prescription drugs.
"When I see a company doing this crap, it makes me insane,” he said.
But, now, CVS has reversed the price high.
"Justice had been served,” Curt told us.
When Curt originally went to the CVS pharmacy in Maple Grove last Spring, the initial 30-day supply cost about $.87 per pill.
But when he followed his insurance company’s advice and ordered a 90-day supply through the mail, CVS Caremark increased the price to more than $6 a pill.
After KARE 11 called CVS they rolled the price back and gave Curt a refund.
Which raises the question: If transparency proponents were intellectually honest (some are, most are not) they would demand the same openness from every health care institution that shapes access to and the price of medicines.
Will PBMs and insurers reveal how they move from drugs that they acquire at 40-60 percent below pharmacy retail prices to charging consumers 30 percent of that retail price?
Will PBMs and insurers reveal how and why they decide when their customers are forced to fail first on medicines?
We need to know. They claim drug costs are climbing at an unsustainable rate. That doesn’t square with data since 2000, spending on drugs has remained at 9-10 percent or HHS projections that overall drugs will remain at about 9 percent of total health spending through 2030. So why are copays and co-insurance rates increasing??
Will hospitals reveal how they go from drugs acquired at the same rate to charging up to 700 percent of retail prices? And while they are at it, will they explain why charges for hospital care increased faster than drugs, even as the use of these new medicines reduce hospital costs? Why has hospital spending increased 6 times faster than drug spending between 2010-2013?
If I am a pharmaceutical company, I’d be for transparency for everyone. I’d show them mine, if they showed theirs. Let’s have the Full Monty for all.
Take this story from Minneapolis.
A major company has rolled back the price of a potentially life-saving prescription drug after a KARE 11 News investigation.
But the decision has some people asking how often we’re being overcharged on other medicines.
Curt’s Story
It started with Curt Burshem.
Back in November he told us CVS Caremark had jacked up the price for a prescription drug a family member needed for a kidney disorder.
Curt Burshem discovered that CVS was overcharging him on prescription drugs.
"When I see a company doing this crap, it makes me insane,” he said.
But, now, CVS has reversed the price high.
"Justice had been served,” Curt told us.
When Curt originally went to the CVS pharmacy in Maple Grove last Spring, the initial 30-day supply cost about $.87 per pill.
But when he followed his insurance company’s advice and ordered a 90-day supply through the mail, CVS Caremark increased the price to more than $6 a pill.
After KARE 11 called CVS they rolled the price back and gave Curt a refund.
Which raises the question: If transparency proponents were intellectually honest (some are, most are not) they would demand the same openness from every health care institution that shapes access to and the price of medicines.
Will PBMs and insurers reveal how they move from drugs that they acquire at 40-60 percent below pharmacy retail prices to charging consumers 30 percent of that retail price?
Will PBMs and insurers reveal how and why they decide when their customers are forced to fail first on medicines?
We need to know. They claim drug costs are climbing at an unsustainable rate. That doesn’t square with data since 2000, spending on drugs has remained at 9-10 percent or HHS projections that overall drugs will remain at about 9 percent of total health spending through 2030. So why are copays and co-insurance rates increasing??
Will hospitals reveal how they go from drugs acquired at the same rate to charging up to 700 percent of retail prices? And while they are at it, will they explain why charges for hospital care increased faster than drugs, even as the use of these new medicines reduce hospital costs? Why has hospital spending increased 6 times faster than drug spending between 2010-2013?
If I am a pharmaceutical company, I’d be for transparency for everyone. I’d show them mine, if they showed theirs. Let’s have the Full Monty for all.
Within days of being given a diphtheria jab during a school vaccination drive, 5-year-old Meraj Shabbir Khan's leg became so swollen that he was hospitalised.
In a cramped Mumbai paediatric ward, third-year pharmacology student Nitin Shinde opens the boy's file and notes the vaccine, his age and the doctor's diagnosis of a skin infection. That information is later logged into a computer programme linked to a national database, part of India's fledgling efforts to track, analyse and ultimately warn patients about unknown side effects of drugs on the market.
India's six-year-old pharmacovigilance programme, which collects and submits suspected adverse drug reactions to a World Health Organisation (WHO) database, is key to improving drug safety in a country where medicine consumption is high, experts say.
But insufficient staff and equipment, and a lack of awareness among medical professionals mean many potentially dangerous drug reactions go unrecorded, hospital personnel across India told Reuters.
Gaps in the system mean the government has less data to determine whether drugs might have harmful side effects. Also, relatively little information flows from one of the world's largest pharmaceutical markets to the WHO database of over 12 million suspected adverse drug reactions.
"In a country of 1 billion people consuming so much medicine, obviously safety is a concern," said G. Parthasarathi, dean of the pharmacy school at JSS University in Mysore, adding the pharmacovigilance programme is still gaining traction. "We've made a good start," he said.
Last year, India contributed 2 percent of the 2.1 million suspected reactions added to VigiBase, the WHO's global database. China, with a comparable population, contributed 8 percent.
Indian health officials say the monitoring programme is a "high priority" and a $14.5 million annual budget is sufficient.
"We are going to develop a better pharmacovigilance system in India in due course," said G.N. Singh, India's drug controller. "Patient health will be assured."
Regarding doctors' lack of engagement, "the culture of reporting is improving," said V. Kalaiselvan, principal scientific officer at the Indian Pharmacopoeia Commission.
The full Reuters article can be found here.
In a cramped Mumbai paediatric ward, third-year pharmacology student Nitin Shinde opens the boy's file and notes the vaccine, his age and the doctor's diagnosis of a skin infection. That information is later logged into a computer programme linked to a national database, part of India's fledgling efforts to track, analyse and ultimately warn patients about unknown side effects of drugs on the market.
India's six-year-old pharmacovigilance programme, which collects and submits suspected adverse drug reactions to a World Health Organisation (WHO) database, is key to improving drug safety in a country where medicine consumption is high, experts say.
But insufficient staff and equipment, and a lack of awareness among medical professionals mean many potentially dangerous drug reactions go unrecorded, hospital personnel across India told Reuters.
Gaps in the system mean the government has less data to determine whether drugs might have harmful side effects. Also, relatively little information flows from one of the world's largest pharmaceutical markets to the WHO database of over 12 million suspected adverse drug reactions.
"In a country of 1 billion people consuming so much medicine, obviously safety is a concern," said G. Parthasarathi, dean of the pharmacy school at JSS University in Mysore, adding the pharmacovigilance programme is still gaining traction. "We've made a good start," he said.
Last year, India contributed 2 percent of the 2.1 million suspected reactions added to VigiBase, the WHO's global database. China, with a comparable population, contributed 8 percent.
Indian health officials say the monitoring programme is a "high priority" and a $14.5 million annual budget is sufficient.
"We are going to develop a better pharmacovigilance system in India in due course," said G.N. Singh, India's drug controller. "Patient health will be assured."
Regarding doctors' lack of engagement, "the culture of reporting is improving," said V. Kalaiselvan, principal scientific officer at the Indian Pharmacopoeia Commission.
The full Reuters article can be found here.
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.
