Latest Drugwonks' Blog
If Brexit, whither EMA?
Will Great Britain become like Norway and Iceland, attending committees such as the CHMP, where their views and votes are not of the same standing as those of members of the EU, or choose to follow a different route? There’s a lot at stake for the future of the MHRA and the British public health.
But what about the impact of removing MHRA expertise from EMA?
According to “Perplexit,” by BioCentury’s Steve Usdin, there’s a lot for EMA to worry about. “Since the start of EMA, MHRA has been a major supplier of resources and scientific expertise,” former EMA Executive Director Thomas Lönngren told BioCentury.
Of the 3,678 scientific experts listed in an EMA database, 281, or 8%, are from the U.K. “Taking a leading role in providing scientific and regulatory advice at the European level is a position the agency is familiar with and has maintained this year,” MHRA stated in its 2015 annual report. The U.K. drug regulator noted that in 2014-15 it was given 166 appointments to coordinate CHMP Scientific Advice Working Parties, a figure which represented “the highest number of any member state and reflects the high regard in which the agency’s scientific and regulatory expertise is held.”
MHRA also continued to “have the highest number of rapporteur/corapporteur appointments in Europe” in 2014-15. The agency said the workload is an acknowledgement of the “widely respected knowledge of the MHRA and its assessment processes.”
Since EMA’s creation, MHRA officials have served as rapporteurs for 16.5% of CHMP assessments and as co-rapporteurs for 10% of assessments.
MHRA experts have played a major role in pharmacovigilance assessments, serving as rapporteurs or co-rapporteurs for 29% of Pharmacovigilance Risk Assessment Committee (PRAC) safety investigations.
In addition to leading assessments of applications submitted under EMA’s centralized procedure, the U.K. and MHRA are a top choice for companies using the decentralized procedure to obtain marketing authorizations in several EU countries.
Applicants can select a reference member state (RMS) for decentralized authorizations. In 2014-15 the U.K. “remained the preferred RMS responsible for leading on 195 (45%) of all procedures in which the U.K. was involved,” according to the MHRA annual report.
The U.K. agency has taken a leading position in developing EMA regulatory policies, BioIndustry Association CEO Steve Bates told BioCentury. He cited initiatives to revamp the clinical trials directive into a regulation that will facilitate multisite, multinational trials, EMA’s policies on advanced therapies such as gene and cellular therapies, and the PRIority MEdicines (PRIME) initiative, EMA’s version of FDA’s breakthrough therapies program.
Whatever arrangement is negotiated, a Brexit will likely force EMA and its 890 employees to leave its base in London’s Canary Wharf. EMA employs 60 British nationals, and about 10% of its management positions are held by Brits.
With EMA moving to the continent, and MHRA’s loss of status within EMA, will pharmaceutical companies to move their regulatory hubs out of the U.K. To do otherwise, according to Grant Castle, a partner in the London office of the law firm Covington & Burling, “would be like having European marketing authorizations maintained by staff in the U.S., Switzerland or Japan.”
Warsaw here we come?
Will Great Britain become like Norway and Iceland, attending committees such as the CHMP, where their views and votes are not of the same standing as those of members of the EU, or choose to follow a different route? There’s a lot at stake for the future of the MHRA and the British public health.
But what about the impact of removing MHRA expertise from EMA?
According to “Perplexit,” by BioCentury’s Steve Usdin, there’s a lot for EMA to worry about. “Since the start of EMA, MHRA has been a major supplier of resources and scientific expertise,” former EMA Executive Director Thomas Lönngren told BioCentury.
Of the 3,678 scientific experts listed in an EMA database, 281, or 8%, are from the U.K. “Taking a leading role in providing scientific and regulatory advice at the European level is a position the agency is familiar with and has maintained this year,” MHRA stated in its 2015 annual report. The U.K. drug regulator noted that in 2014-15 it was given 166 appointments to coordinate CHMP Scientific Advice Working Parties, a figure which represented “the highest number of any member state and reflects the high regard in which the agency’s scientific and regulatory expertise is held.”
MHRA also continued to “have the highest number of rapporteur/corapporteur appointments in Europe” in 2014-15. The agency said the workload is an acknowledgement of the “widely respected knowledge of the MHRA and its assessment processes.”
Since EMA’s creation, MHRA officials have served as rapporteurs for 16.5% of CHMP assessments and as co-rapporteurs for 10% of assessments.
MHRA experts have played a major role in pharmacovigilance assessments, serving as rapporteurs or co-rapporteurs for 29% of Pharmacovigilance Risk Assessment Committee (PRAC) safety investigations.
In addition to leading assessments of applications submitted under EMA’s centralized procedure, the U.K. and MHRA are a top choice for companies using the decentralized procedure to obtain marketing authorizations in several EU countries.
Applicants can select a reference member state (RMS) for decentralized authorizations. In 2014-15 the U.K. “remained the preferred RMS responsible for leading on 195 (45%) of all procedures in which the U.K. was involved,” according to the MHRA annual report.
The U.K. agency has taken a leading position in developing EMA regulatory policies, BioIndustry Association CEO Steve Bates told BioCentury. He cited initiatives to revamp the clinical trials directive into a regulation that will facilitate multisite, multinational trials, EMA’s policies on advanced therapies such as gene and cellular therapies, and the PRIority MEdicines (PRIME) initiative, EMA’s version of FDA’s breakthrough therapies program.
Whatever arrangement is negotiated, a Brexit will likely force EMA and its 890 employees to leave its base in London’s Canary Wharf. EMA employs 60 British nationals, and about 10% of its management positions are held by Brits.
With EMA moving to the continent, and MHRA’s loss of status within EMA, will pharmaceutical companies to move their regulatory hubs out of the U.K. To do otherwise, according to Grant Castle, a partner in the London office of the law firm Covington & Burling, “would be like having European marketing authorizations maintained by staff in the U.S., Switzerland or Japan.”
Warsaw here we come?
Important news. FDA Commissioner Robert Califf outlined two draft guidance documents addressing regulatory approval of next-generation sequencing (NGS)-based diagnostics. The guidances were presented as part of an update on the White House's Precision Medicine Initiative, which is recruiting a cohort of 1 million volunteers for a longitudinal research study.
The first guidance, titled "Use of Standards in FDA's Regulatory Oversight of Next Generation Sequencing (NGS)-based In Vitro Diagnostics (IVDs) Used for Diagnosing Germline Diseases," describes FDA-recognized standards to demonstrate test accuracy and provides recommendations for designing, developing and validating NGS-based tests for hereditary diseases.
FDA said a second guidance, titled "Use of Public Human Genetic Variant Databases to Support Clinical Validity for Next Generation Sequencing (NGS)-based In Vitro Diagnostics" outlines "an easier path for marketing clearance or approval" of NGS tests that would allow developers to use genomic databases to support clinical claims.
Per a report in BioCentury, “Califf said the draft guidances are meant to strike a balance between encouraging innovation and supporting patient safety.” FDA will accept comments on the guidance for 90 days.
The first guidance, titled "Use of Standards in FDA's Regulatory Oversight of Next Generation Sequencing (NGS)-based In Vitro Diagnostics (IVDs) Used for Diagnosing Germline Diseases," describes FDA-recognized standards to demonstrate test accuracy and provides recommendations for designing, developing and validating NGS-based tests for hereditary diseases.
FDA said a second guidance, titled "Use of Public Human Genetic Variant Databases to Support Clinical Validity for Next Generation Sequencing (NGS)-based In Vitro Diagnostics" outlines "an easier path for marketing clearance or approval" of NGS tests that would allow developers to use genomic databases to support clinical claims.
Per a report in BioCentury, “Califf said the draft guidances are meant to strike a balance between encouraging innovation and supporting patient safety.” FDA will accept comments on the guidance for 90 days.
From the pages of the Boston Globe and reporter Ed Silverman ...
Independence would be good for the FDA and the public
In a moment remarkable for its symbolism, six former Food and Drug Administration commissioners last month sat together on a stage and argued that their former agency needs more autonomy from Washington bureaucracy. The solution: make the FDA independent and maybe give it a cabinet seat at the White House, too.
The idea has been kicked around a few times over the years, but never gained traction. Yet the panel discussion at the Aspen Ideas Festival has refocused attention on the notion that the FDA — and by extension, the American public — would be better off if the agency’s status was elevated. And the suggestion carried still more weight since the former commissioners worked for both Republican and Democratic administrations.
Right now, the FDA is part of the US Department of Health and Human Services, which adds a big layer of officialdom between the agency and the White House. And in a legislative holdover, the FDA budget is overseen by House and Senate agriculture appropriations committees, which may not always be familiar with matters surrounding cutting-edge medical developments.
“An independent agency could work directly with Congress and the White House on a one-to-one basis and create dialogue that could lead to policy changes,” Andrew von Eschenbach, who was FDA commissioner from 2006 through 2009, and is now president Samaritan Health Initiatives, a think tank, told me. “This would put FDA in a much better position to execute its mission.”
To what extent the notion can become reality is uncertain, but it’s worth considering.
Here’s one reason. In December 2011, former HHS Secretary Kathleen Sebelius overruled the FDA and refused to allow an emergency contraceptive pill to be sold over the counter to young teens. This was the first time the HHS took such a step, but it was politically expedient because it allowed the Obama administration to avoid a contentious battle over birth control during a presidential election season.
The decision smacked of malfeasance, but reflected a long-running battle between politicians and scientists over whether the “morning after” pill should be available without a prescription. The Bush administration initially resisted such a move but later allowed over-the-counter access to women 18 and older. In 2009, the Obama administration lowered the age to 17 in response to a federal court order.
Of course, it’s true that even an independent FDA would still remain beholden to the White House, which suggests the potential for political interference will always exist. This is a fact of life in Washington. But cabinet-level status may confer an added benefit, because whoever heads the FDA would, presumably, have more opportunity for direct contact with administration decision makers.
“It may not entirely change the political dynamic, but I think it would be an improvement, because it could make it more difficult to meddle,” said Peter Pitts, a former FDA associate commissioner, who heads the Center for Medicine in the Public Interest, a think tank that is funded, in part, by industry. “You want to make it possible for a commissioner to stand firm and do the right thing,” added Pitts who wasn’t at the Aspen conference.
Toward that end, the top FDA job might also be structured so that there is a fixed term of say, six years, that doesn’t directly overlap with a president’s tenure. Yes, the FDA chief would still be a political appointee, but this approach may encourage a midterm president to find the best candidate, rather than use the appointment as a way to pay a political debt following an election.
Another reason to consider a push for independence is the budget process. Since FDA is part of HHS, its budget is vulnerable to cuts and changes — even before Congress gets to decide what to leave in and what to leave out. By elevating the agency to cabinet-level status, the FDA presumably could have more sway over resources.
“In a way, the FDA has always been a stepchild,” said Ira Loss of Washington Analysis, a consulting firm that tracks the pharmaceutical industry and regulatory policy. “And it often gets trapped in the bureaucracy.”
The challenge is to make a good case for independence.
Right now, the odds seem long. A new administration would have to be convinced to make the idea a priority. And persuading Congress, which seems perennially critical of the FDA and is currently crafting legislation to remake some agency functions, would be a challenge. To speed things along, von Eschenbach noted that a few former commissioners may now consider drafting a joint white paper.
To be sure, there will always be bureaucratic hurdles. That’s the nature of government. But any effort that can recalibrate the balance between bureaucracy and resources should be pursued. The FDA deserves a seat at the table where decisions are made.
Independence would be good for the FDA and the public
In a moment remarkable for its symbolism, six former Food and Drug Administration commissioners last month sat together on a stage and argued that their former agency needs more autonomy from Washington bureaucracy. The solution: make the FDA independent and maybe give it a cabinet seat at the White House, too.
The idea has been kicked around a few times over the years, but never gained traction. Yet the panel discussion at the Aspen Ideas Festival has refocused attention on the notion that the FDA — and by extension, the American public — would be better off if the agency’s status was elevated. And the suggestion carried still more weight since the former commissioners worked for both Republican and Democratic administrations.
Right now, the FDA is part of the US Department of Health and Human Services, which adds a big layer of officialdom between the agency and the White House. And in a legislative holdover, the FDA budget is overseen by House and Senate agriculture appropriations committees, which may not always be familiar with matters surrounding cutting-edge medical developments.
“An independent agency could work directly with Congress and the White House on a one-to-one basis and create dialogue that could lead to policy changes,” Andrew von Eschenbach, who was FDA commissioner from 2006 through 2009, and is now president Samaritan Health Initiatives, a think tank, told me. “This would put FDA in a much better position to execute its mission.”
To what extent the notion can become reality is uncertain, but it’s worth considering.
Here’s one reason. In December 2011, former HHS Secretary Kathleen Sebelius overruled the FDA and refused to allow an emergency contraceptive pill to be sold over the counter to young teens. This was the first time the HHS took such a step, but it was politically expedient because it allowed the Obama administration to avoid a contentious battle over birth control during a presidential election season.
The decision smacked of malfeasance, but reflected a long-running battle between politicians and scientists over whether the “morning after” pill should be available without a prescription. The Bush administration initially resisted such a move but later allowed over-the-counter access to women 18 and older. In 2009, the Obama administration lowered the age to 17 in response to a federal court order.
Of course, it’s true that even an independent FDA would still remain beholden to the White House, which suggests the potential for political interference will always exist. This is a fact of life in Washington. But cabinet-level status may confer an added benefit, because whoever heads the FDA would, presumably, have more opportunity for direct contact with administration decision makers.
“It may not entirely change the political dynamic, but I think it would be an improvement, because it could make it more difficult to meddle,” said Peter Pitts, a former FDA associate commissioner, who heads the Center for Medicine in the Public Interest, a think tank that is funded, in part, by industry. “You want to make it possible for a commissioner to stand firm and do the right thing,” added Pitts who wasn’t at the Aspen conference.
Toward that end, the top FDA job might also be structured so that there is a fixed term of say, six years, that doesn’t directly overlap with a president’s tenure. Yes, the FDA chief would still be a political appointee, but this approach may encourage a midterm president to find the best candidate, rather than use the appointment as a way to pay a political debt following an election.
Another reason to consider a push for independence is the budget process. Since FDA is part of HHS, its budget is vulnerable to cuts and changes — even before Congress gets to decide what to leave in and what to leave out. By elevating the agency to cabinet-level status, the FDA presumably could have more sway over resources.
“In a way, the FDA has always been a stepchild,” said Ira Loss of Washington Analysis, a consulting firm that tracks the pharmaceutical industry and regulatory policy. “And it often gets trapped in the bureaucracy.”
The challenge is to make a good case for independence.
Right now, the odds seem long. A new administration would have to be convinced to make the idea a priority. And persuading Congress, which seems perennially critical of the FDA and is currently crafting legislation to remake some agency functions, would be a challenge. To speed things along, von Eschenbach noted that a few former commissioners may now consider drafting a joint white paper.
To be sure, there will always be bureaucratic hurdles. That’s the nature of government. But any effort that can recalibrate the balance between bureaucracy and resources should be pursued. The FDA deserves a seat at the table where decisions are made.
From the pages of this morning's Morning Consult:
JAMA and Pharma Freebies: Same Slander. Different Day.
The truth is rarely pure and never simple. -- Oscar Wilde
Much ado about pharma freebies to physicians. Much ado about nothing medically and everything politically.
A new study published by JAMA Internal Medicine (Pharmaceutical Industry–Sponsored Meals and Physician Prescribing Patterns for Medicare Beneficiaries) makes it sound (as Meagan McArdle has written for Bloomberg), that your doctor is “willing to sell you out for the price of a sandwich.” It’s not that simple … or true.
The JAMA methodology:
Cross-sectional study of 279,669 physicians that received industry-sponsored meals (retrieved from Open Payments program) and wrote Medicare part D prescriptions in any of four drug classes: statins, cardioselective beta blockers, angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers (ACE inhibitors and ARBs) and selective serotonin reuptake inhibitors (SSRIs)/serotonin norepinephrine reuptake inhibitors (SNRIs). Prescribing rates of promoted medicines were compared with in-class alternatives adjusted for volume, demographic characteristics, specialty and practice setting.
It’s important to note up front the JAMA conclusion stated that, “The findings represent an association and not a cause and effect relationship.” But you won’t find that in the media coverage. Also, the Open Payments data and Medicare Part D prescription data are not temporally linked. As John Adams points out, “Facts are pesky things.”
Mechanism of association cannot be extrapolated from the methodology of the study; systematic confounding variables such as physician self-selection to attend the educational event and the effect of education itself obscure interpretation of the results. The study design is cross-sectional, only 5 months of payment data may not be representative of a full year and beyond. And, importantly, branded medicines that are often newer may represent advances over older generic agents with regard to efficacy and tolerability.
This is not a new debate nor is it new to the pages of the Journal of the American Medical Association. A widely cited 2000 JAMA article in summarized 29 published studies critiquing the interaction between doctors and drug reps. Notable feature of these articles, as quoted in the summary paper: "No study used patient outcome measures." Absent in 2000 and in 2016 was any discussion of how diagnostic and dispensing decisions are often influenced by external cost-control measures. Both JAMA articles allowed politics to trump the public health. The polite term for this is “normative bias.”
Studies and commentary that discuss alternative findings are generally ignored. In the February 7, 2009 edition of The Lancet, Richard Horton points out that the battle lines being drawn and between clinician, medical research and the pharmaceutical industry are artificial at best -- and dangerous at worst. Dangerous, because all three constituencies are working towards the same goal -- improved patient outcomes. His main point is that we must dismantle the battlements and embrace of philosophy of "symbiosis not schism." It's what's in the best interest of the patient.
Information is an important lubricant for markets and yields numerous benefits to market participants. Open, honest, and regular communication is critical for alerting both doctors and patients as to what medicines are available, and for what diseases. No single person, especially a general practitioner, can keep up with all of the information available on drugs, let alone health care. By one estimate every year some 1,700 articles are published in each of 325 professional journals on the 25 top medicines. Drug producers use a variety of promotional efforts to stand out in this information flood. One may like or hate the industry’s tactics, but there is nothing illegitimate about them.
Per Dennis Ausiello and Thomas P. Stossel (both of Harvard Medical School):
The real intent of these critics goes far beyond food and trinkets, and its true purpose is to curtail strictly or even eliminate all contacts between physicians and private industry. We strongly oppose this agenda. Despite extensive training, physicians cannot know the details of all products, especially new ones. Therefore, company salespersons complement physicians’ information derived from many sources. They tell physicians about a limited range of products about which their employers train them under strict FDA regulations. We believe that the best approach to optimize cost effectiveness of product prescribing is to promote more, not less, interaction among all stakeholders involved in health-care delivery, including company marketing reps.
From a strictly free market perspective, if there were only one drug company, there would be for that entity to speak with physicians. But who marketed anything in the Soviet Union? Imperfect though the process might be, marketing promotes price competition and lowers prices.
According to Paul H, Rubin, Professor of Law and Economics at Emory University and former Chief Advertising Economist at the Federal Trade Commission and Chief Economist at the U.S. Consumer Product Safety Commission:
Drug company reps offer overworked doctors useful, lifesaving information in an efficient manner. The drug companies are of course motivated by profit, but economists have known since Adam Smith that the profit motive is the best way to induce someone to do something useful. Marketing and research are both information activities; they work together to get effective drugs to patients. The two activities are not in competition for resources. The denouncers of drug companies don't understand this. One of the senators sponsoring the bill suggests that "the millions of dollars these companies spend on marketing ... could be put into research." In fact, drug companies would not switch money from marketing to research. If they cannot market drugs in the best way, they will reduce spending on research. What's the point of inventing a new drug if doctors and patients don't know about it?
This is crucial -- in all of the medical literature on drug sales, there was no evidence of harm to patients caused by doctors and drug reps sharing a few slices of pizza. Physicians who, by their oaths put patient welfare first wrote these articles. Yet they were critical of the industry based on analyses that totally ignore the only measure that really counts – patient outcomes.
“Good for sales” and “Good for the public health” are not mutually exclusive.
A valuable takeaway from the new JAMA study should be that wide adoption of Open Payments reporting has led to transparent interactions and value exchanges of education, money and meals between the pharmaceutical industry and prescribers. These data are now available to inform and improve educational efforts to meet the treatment needs of patients using the latest advances in medicine and science. However, such data must be cautiously interpreted with full acknowledgement of study limitations and author bias.
In summary, the new JAMA study is devoid of any data regarding patient outcomes; omits all the variables physicians consider when treating their patients; assumes pharmaceutical sponsored meals are purely social gatherings in which no educational information is shared; and reduces complex prescribing decisions to a simple transaction.
“The best interest of the patient is the only interest to be considered.” -- William Mayo, MD
JAMA and Pharma Freebies: Same Slander. Different Day.
The truth is rarely pure and never simple. -- Oscar Wilde
Much ado about pharma freebies to physicians. Much ado about nothing medically and everything politically.
A new study published by JAMA Internal Medicine (Pharmaceutical Industry–Sponsored Meals and Physician Prescribing Patterns for Medicare Beneficiaries) makes it sound (as Meagan McArdle has written for Bloomberg), that your doctor is “willing to sell you out for the price of a sandwich.” It’s not that simple … or true.
The JAMA methodology:
Cross-sectional study of 279,669 physicians that received industry-sponsored meals (retrieved from Open Payments program) and wrote Medicare part D prescriptions in any of four drug classes: statins, cardioselective beta blockers, angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers (ACE inhibitors and ARBs) and selective serotonin reuptake inhibitors (SSRIs)/serotonin norepinephrine reuptake inhibitors (SNRIs). Prescribing rates of promoted medicines were compared with in-class alternatives adjusted for volume, demographic characteristics, specialty and practice setting.
It’s important to note up front the JAMA conclusion stated that, “The findings represent an association and not a cause and effect relationship.” But you won’t find that in the media coverage. Also, the Open Payments data and Medicare Part D prescription data are not temporally linked. As John Adams points out, “Facts are pesky things.”
Mechanism of association cannot be extrapolated from the methodology of the study; systematic confounding variables such as physician self-selection to attend the educational event and the effect of education itself obscure interpretation of the results. The study design is cross-sectional, only 5 months of payment data may not be representative of a full year and beyond. And, importantly, branded medicines that are often newer may represent advances over older generic agents with regard to efficacy and tolerability.
This is not a new debate nor is it new to the pages of the Journal of the American Medical Association. A widely cited 2000 JAMA article in summarized 29 published studies critiquing the interaction between doctors and drug reps. Notable feature of these articles, as quoted in the summary paper: "No study used patient outcome measures." Absent in 2000 and in 2016 was any discussion of how diagnostic and dispensing decisions are often influenced by external cost-control measures. Both JAMA articles allowed politics to trump the public health. The polite term for this is “normative bias.”
Studies and commentary that discuss alternative findings are generally ignored. In the February 7, 2009 edition of The Lancet, Richard Horton points out that the battle lines being drawn and between clinician, medical research and the pharmaceutical industry are artificial at best -- and dangerous at worst. Dangerous, because all three constituencies are working towards the same goal -- improved patient outcomes. His main point is that we must dismantle the battlements and embrace of philosophy of "symbiosis not schism." It's what's in the best interest of the patient.
Information is an important lubricant for markets and yields numerous benefits to market participants. Open, honest, and regular communication is critical for alerting both doctors and patients as to what medicines are available, and for what diseases. No single person, especially a general practitioner, can keep up with all of the information available on drugs, let alone health care. By one estimate every year some 1,700 articles are published in each of 325 professional journals on the 25 top medicines. Drug producers use a variety of promotional efforts to stand out in this information flood. One may like or hate the industry’s tactics, but there is nothing illegitimate about them.
Per Dennis Ausiello and Thomas P. Stossel (both of Harvard Medical School):
The real intent of these critics goes far beyond food and trinkets, and its true purpose is to curtail strictly or even eliminate all contacts between physicians and private industry. We strongly oppose this agenda. Despite extensive training, physicians cannot know the details of all products, especially new ones. Therefore, company salespersons complement physicians’ information derived from many sources. They tell physicians about a limited range of products about which their employers train them under strict FDA regulations. We believe that the best approach to optimize cost effectiveness of product prescribing is to promote more, not less, interaction among all stakeholders involved in health-care delivery, including company marketing reps.
From a strictly free market perspective, if there were only one drug company, there would be for that entity to speak with physicians. But who marketed anything in the Soviet Union? Imperfect though the process might be, marketing promotes price competition and lowers prices.
According to Paul H, Rubin, Professor of Law and Economics at Emory University and former Chief Advertising Economist at the Federal Trade Commission and Chief Economist at the U.S. Consumer Product Safety Commission:
Drug company reps offer overworked doctors useful, lifesaving information in an efficient manner. The drug companies are of course motivated by profit, but economists have known since Adam Smith that the profit motive is the best way to induce someone to do something useful. Marketing and research are both information activities; they work together to get effective drugs to patients. The two activities are not in competition for resources. The denouncers of drug companies don't understand this. One of the senators sponsoring the bill suggests that "the millions of dollars these companies spend on marketing ... could be put into research." In fact, drug companies would not switch money from marketing to research. If they cannot market drugs in the best way, they will reduce spending on research. What's the point of inventing a new drug if doctors and patients don't know about it?
This is crucial -- in all of the medical literature on drug sales, there was no evidence of harm to patients caused by doctors and drug reps sharing a few slices of pizza. Physicians who, by their oaths put patient welfare first wrote these articles. Yet they were critical of the industry based on analyses that totally ignore the only measure that really counts – patient outcomes.
“Good for sales” and “Good for the public health” are not mutually exclusive.
A valuable takeaway from the new JAMA study should be that wide adoption of Open Payments reporting has led to transparent interactions and value exchanges of education, money and meals between the pharmaceutical industry and prescribers. These data are now available to inform and improve educational efforts to meet the treatment needs of patients using the latest advances in medicine and science. However, such data must be cautiously interpreted with full acknowledgement of study limitations and author bias.
In summary, the new JAMA study is devoid of any data regarding patient outcomes; omits all the variables physicians consider when treating their patients; assumes pharmaceutical sponsored meals are purely social gatherings in which no educational information is shared; and reduces complex prescribing decisions to a simple transaction.
“The best interest of the patient is the only interest to be considered.” -- William Mayo, MD
Draft Democratic platform calls for both drug importation and direct Federeal negotiation for Medicare and Medicaid.
Populist rhetoric isn't good for the public health.
"Facts," as John Adams said, "are pesky things."
Populist rhetoric isn't good for the public health.
"Facts," as John Adams said, "are pesky things."
Pharmaceutical innovation has not only revolutionized the field of health care and significantly contributed to the fight against cancer, but it also allows Canadian governments to save billions of dollars. This is the general thrust of a Research Paper published today by the MEI, prepared by Frank R. Lichtenberg, Professor at the Columbia University Graduate School of Business and internationally renowned expert in this field of research.
Taking into account just the effects of new cancer drugs, Canadian governments registered savings of $4.7 billion in hospital expenditure in 2012 alone, whereas total spending on cancer drugs, old and new, was an estimated $3.8 billion that same year.
“If no new drugs had been registered from 1980 to 1997, the number of hospital days in 2012 would have been almost twice as high,” says Professor Lichtenberg, who has published numerous articles on the issue in a variety of scientific journals. “This represents in one single year net savings of at least $900 million for the Canadian health care system.”
The costs of new pharmaceuticals are often the subject of critical media coverage, but their benefits are rarely mentioned. Yet pharmaceutical innovation is responsible for a large part of long-term improvements in the health and longevity of patients.
For example, the premature (before age 75) cancer mortality rate declined by 8.4% from 2000 to 2011 in Canada. This rate would instead have increased by 12.3% in the absence of pharmaceutical innovation, implying that 105,366 years of potential life before age 75 would have been lost in 2011 alone.
“Although new drugs are expensive, this cost is small when compared with the benefits they provide for patients,” argues Professor Lichtenberg.
The publication also points out that financial incentives are a prerequisite for the industry to sustain a robust rate of pharmaceutical innovation. “It is important for drugs to be appropriately priced in order for manufacturers to have the proper incentives to invest in the development of new molecules, a very risky process that can be very expensive for the innovating company,” argues Youri Chassin, Research Director at the MEI.
The Research Paper entitled The Benefits of Pharmaceutical Innovation: Health, Longevity, and Savings was prepared by Frank R. Lichtenberg, Courtney C. Brown Professor at Columbia University Graduate School of Business and Associate Researcher at the Montreal Economic Institute. This publication is available here.
Taking into account just the effects of new cancer drugs, Canadian governments registered savings of $4.7 billion in hospital expenditure in 2012 alone, whereas total spending on cancer drugs, old and new, was an estimated $3.8 billion that same year.
“If no new drugs had been registered from 1980 to 1997, the number of hospital days in 2012 would have been almost twice as high,” says Professor Lichtenberg, who has published numerous articles on the issue in a variety of scientific journals. “This represents in one single year net savings of at least $900 million for the Canadian health care system.”
The costs of new pharmaceuticals are often the subject of critical media coverage, but their benefits are rarely mentioned. Yet pharmaceutical innovation is responsible for a large part of long-term improvements in the health and longevity of patients.
For example, the premature (before age 75) cancer mortality rate declined by 8.4% from 2000 to 2011 in Canada. This rate would instead have increased by 12.3% in the absence of pharmaceutical innovation, implying that 105,366 years of potential life before age 75 would have been lost in 2011 alone.
“Although new drugs are expensive, this cost is small when compared with the benefits they provide for patients,” argues Professor Lichtenberg.
The publication also points out that financial incentives are a prerequisite for the industry to sustain a robust rate of pharmaceutical innovation. “It is important for drugs to be appropriately priced in order for manufacturers to have the proper incentives to invest in the development of new molecules, a very risky process that can be very expensive for the innovating company,” argues Youri Chassin, Research Director at the MEI.
The Research Paper entitled The Benefits of Pharmaceutical Innovation: Health, Longevity, and Savings was prepared by Frank R. Lichtenberg, Courtney C. Brown Professor at Columbia University Graduate School of Business and Associate Researcher at the Montreal Economic Institute. This publication is available here.
After concluding that because myeloma drugs keep people alive longer they cost too much to be cost-effective, ICER through it’s Midwest Comparative Effectiveness Public Advisory Council (Midwest CEPAC) is now looking at new drugs for treating people with non small lung cancer.
And ICER’s Steve Pearson wants you to know that he and his organization care about patients. ICER’s website has a video of Pearson speaking before the Midwest CEPAC meeting entitled: “Why we are here today” – Dr. Pearson underscores the moral vision of the Midwest CEPAC” (Yes, that's the title
In proclaiming this moral vision Pearson said: “we really want to know from patients what outcomes matter most to them.”
He also claims that the quality adjusted life year does not mean a life is “less valuable if they have or disability. a gain is a gain wherever you are starting from. Sometimes there are conditions where we have a serious condition and the first possible treatment, that’s an important consideration.”
These are outright falsehoods that hide Pearson’s real moral vision.
Pearson – and ICER – are using a superficially low QALY measure that does NOT take into account what matters to patients, by overstating and misrepresenting the price of new medicines and by clearly using budget caps to cut off and ration care.
And ICER’s metrics and methods are indeed driven by Pearson’s moral vision which he stated clearly in an article entitled: “Which Orphans Will Find a Home: The Rule of Rescue in Resource Allocation for Rare Diseases” where he tells us what he really thinks about lung cancer patients:
(Spoiler alert: Pearson thinks lung cancer patients are underserving whiners. )
Before directly attacking lung cancer patients, Pearson argues “There is no apparent obligation to rescue identifiable rare disease patients based on a duty of rescue within personal morality.”
But what about, as Pearson said, taking into account new treatments for people with the most serious conditions and few options?
“In practice, however, a sickest-first principle might require allocation of resources even when only minor gains can be achieved and the cost is very high, which is obviously inefficient…coverage decisions must not only incorporate consideration of the benefits gained
but the opportunity costs incurred when covering expensive orphan drugs.
And contrary to Pearson’s claim about not considering cost in recommending what drugs to use, he clearly regards the growing number of expensive therapies that offer benefit only to small populations” to “ensure that an undue burden is not
placed on others for the sake of a few.”
Then Pearson goes on to show that people with non small cell lung cancer aren’t worth spending money on based on his/ICER’s estimate of opportunity cost.
First, he claims, contrary to his desire to engage patients, that patient advocacy is a pain in the ass that gets in the way of making cost-based decisions for the good of all:
“Publicity can be a powerful and important tool for advocacy groups, but it is not an appropriate ethical justification for coverage of particular orphan drugs over others.”
Note that people said the same thing when AIDS activists were demanding faster and broader access to new medicines.
And he singles out people with lung cancer as a patient group that is unethically using advocacy: the pressure to treat every (lung cancer) patient is a product of lobbying and driven largely by the heightened public consciousness surrounding lung cancer.”
With that bias, Pearson then applies ICER’s benchmark for limiting access to new drugs (in this case Erbitux or cetuximab) based on QALY and budget impact:
“Lung cancer is often lethal, but the marginal benefits of cetuximab are quite modest. The average survival advantage from adding cetuximab to the standard treatment regimen is approximately five weeks. Cetuximab treatment is also associated with higher frequencies of rash, diarrhea, and febrile neutropenia, a condition that increases the risk of infection. And, lastly, cetuximab is expensive at both the individual and
population level.
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. " (My note: In fact, Erbitux total revenues worldwide in 2015 were $2.2 billion)
Pearson concludes: “Considering the sources of identifiability (patient advocacy), the marginal impact on the length and quality of life, and the implicit opportunity costs of this level of expenditure, our framework would suggest that public and private insurers would be justified in refusing to pay for cetuximab.”
Pearson believes that unless someone like ICER decides what a life is worth and how much to spend on it, people with rare and fatal conditions – the sickest first -- will be “siphoning off resources for other things we need like better schools and more resources for local police, roads and bridges.”
That’s Pearson’s true moral vision. Refuse to pay for lung cancer drugs and spend the dough on pothole repair.
From the pages of Drug Industry Daily …
Lawmakers, Generics Companies Praise CREATES Act
Senate Judiciary Committee members and generics makers Tuesday both sung the praises of a bill aimed at preventing branded drugmakers from restricting access to their products. The bill is aimed at companies that restrict access to samples, thereby preventing generics companies from reverse-engineering a product, or requesting a distribution safety protocol and then blocking generic companies from participating.
Innovator drug companies came under fire during the subcommittee hearing, with both senators and generic drugmakers accusing them of using the FDA-mandated REMS process to block generic competition.
Beth Zelnick-Kaufman, assistant general counsel at generics maker Amneal Pharmaceuticals, said the CREATES Act “provides necessary remedies” when innovators refuse to provide samples of their product.
Zelnick-Kaufman cited an example of her company attempting to join a brand REMS with an unidentified drugmaker to launch a product designed to treat drug addiction. She said the brand made $1 billion as a result of delay tactics. The unnamed company’s effort to block generic access ended only after the FDA issued its first waiver of the REMS requirement, she said.
Robin Feldman, a professor at the University of California Hastings College Of Law, also applauded the bill. She cited a study she is currently conducting which has found the increase of REMS abuse to be “abundantly clear.” She said the result of REMS abuse delays has cost billions of dollars in savings in recent years.
Only one of the six panelists demonstrated some degree of opposition to the bill. Peter Safir of the law firm Covington & Burling expressed concerns over the consistency of the CREATES Act with the language of the FD&C Act.
Safir notes that FD&C Act includes several civil and criminal penalties that can be brought against drugmakers for violating a single REMS requirement, saying the CREATES Act fails to amend the FD&C Act to protect innovators. He says this can confuse the brand name drugmakers and expose them to enforcement.
Peter Pitts, president and founder of the Center for Medicine in the Public Interest and a former FDA associate commissioner, also expressed some reservations about the bill. He told DID that the bill significantly overreaches what it wants to accomplish, which could result in unintended consequences to patient safety.
Pitts also described the bill as a “get out of jail free card” for generics makers.
PhRMA spokeswoman Holly Campbell told DID that the drug lobby is currently reviewing the legislation, but that it would be concerned if it jeopardizes patient safety in regards to REMS.
The CREATES Act was introduced last week by members of the Senate Judiciary Committee, including Chairman Sen. Chuck Grassley (R-Iowa), ranking member Patrick Leahy (D-Vt.), Sen. Amy Klobuchar (D-Minn.) and Sen. Mike Lee (R-Utah).
The Senate Judiciary Committee did not return a request for comment by press time as to whether a date for a vote has been set.
Lawmakers, Generics Companies Praise CREATES Act
Senate Judiciary Committee members and generics makers Tuesday both sung the praises of a bill aimed at preventing branded drugmakers from restricting access to their products. The bill is aimed at companies that restrict access to samples, thereby preventing generics companies from reverse-engineering a product, or requesting a distribution safety protocol and then blocking generic companies from participating.
Innovator drug companies came under fire during the subcommittee hearing, with both senators and generic drugmakers accusing them of using the FDA-mandated REMS process to block generic competition.
Beth Zelnick-Kaufman, assistant general counsel at generics maker Amneal Pharmaceuticals, said the CREATES Act “provides necessary remedies” when innovators refuse to provide samples of their product.
Zelnick-Kaufman cited an example of her company attempting to join a brand REMS with an unidentified drugmaker to launch a product designed to treat drug addiction. She said the brand made $1 billion as a result of delay tactics. The unnamed company’s effort to block generic access ended only after the FDA issued its first waiver of the REMS requirement, she said.
Robin Feldman, a professor at the University of California Hastings College Of Law, also applauded the bill. She cited a study she is currently conducting which has found the increase of REMS abuse to be “abundantly clear.” She said the result of REMS abuse delays has cost billions of dollars in savings in recent years.
Only one of the six panelists demonstrated some degree of opposition to the bill. Peter Safir of the law firm Covington & Burling expressed concerns over the consistency of the CREATES Act with the language of the FD&C Act.
Safir notes that FD&C Act includes several civil and criminal penalties that can be brought against drugmakers for violating a single REMS requirement, saying the CREATES Act fails to amend the FD&C Act to protect innovators. He says this can confuse the brand name drugmakers and expose them to enforcement.
Peter Pitts, president and founder of the Center for Medicine in the Public Interest and a former FDA associate commissioner, also expressed some reservations about the bill. He told DID that the bill significantly overreaches what it wants to accomplish, which could result in unintended consequences to patient safety.
Pitts also described the bill as a “get out of jail free card” for generics makers.
PhRMA spokeswoman Holly Campbell told DID that the drug lobby is currently reviewing the legislation, but that it would be concerned if it jeopardizes patient safety in regards to REMS.
The CREATES Act was introduced last week by members of the Senate Judiciary Committee, including Chairman Sen. Chuck Grassley (R-Iowa), ranking member Patrick Leahy (D-Vt.), Sen. Amy Klobuchar (D-Minn.) and Sen. Mike Lee (R-Utah).
The Senate Judiciary Committee did not return a request for comment by press time as to whether a date for a vote has been set.
Two recent articles on the alleged negative impact of pharma providing meals to physician practices are first rate examples of how the editors of JAMA and the authors ignore their own questionable data to arrive at a pre-ordained conclusion. And worse, JAMA peddled these articles to the media as proof positive of this claim.
The articles reinforce the assumption that doctors are influenced to prescribe more expensive brand drugs. There is has never been any causal evidence of any sort to support this claim, just anecdotes and the torturing of data that is conducted to fit the narrative.
But let’s say for the sake of argument that the more freebies and lunches doctors received is directly associated with more brand prescribing or specific prescribing of brands. Indeed, that is the hypothesis these two articles seek to test. Except that now, as opposed to even 10 years ago, the amount spent on pharma freebies like lunches and trips worth about $150 has declined. And the number of doctors who get them has fallen too for a number of reasons. At the same time brand prescribing has declined. So the reduction in payments has led to less brand prescribing right?
In Association of Industry Payments to Physicians With the Prescribing of Brand-name Statins in Massachusetts James S. Yeh, MD, MPH; Jessica M. Franklin, PhD; Jerry Avorn, MD; Joan Landon, MPH; Aaron S. Kesselheim, MD, JD, MPH (which I will refer to as Avorn and Co.) claim:
“Industry payments to physicians are associated with higher rates of prescribing brand-name statins. As the United States seeks to reign in the costs of prescription drugs and make them less expensive for patients, our findings are concerning.”
In Pharmaceutical Industry–Sponsored Meals and Physician Prescribing Patterns for Medicare Beneficiaries Colette DeJong, BA concluded:
“Receipt of industry-sponsored meals was associated with an increased rate of prescribing the brand-name medication that was being promoted. The findings represent an association, not a cause-and-effect relationship.”
Dejong and company looked at four specific drugs in different therapeutic class. They note that Crestor was 8.8% statin prescriptions; Benicar 3.3% beta-blocker prescriptions; Benicar was 1.6% of ACE inhibitor and ARB prescriptions; and Prestiq was 0.6% of SSRI and SNRI prescriptions and like Avorn and Co. conclude that prescribing rate was influenced by drug reps passing out donuts and Chipotle.
Except that in both ‘studies’ the brand prescribing rates were BELOW national averages for Medicare part D
The Medicare Payment Advisory Commission reported that
“Generic drugs accounted for 81 percent of all prescriptions filled in 2012 compared with 77 percent and 61 percent in 2011 and 2007, respectively. In 2015, generic fill rate increased again but as Express Scripts Drug Trend Report notes, the fill rates differed by plan type, with Medicare Advantage and stand-alone Part D plans with similar generic fill rates (87.5% and 87.2%, respectively), and Employer Group Waiver Plans with the lowest generic fill rate (82.4%).”
The Avorn group estimated that doctors who got lunch prescribed brand name statins 23 percent of the time vs 18 percent that were deprived of a free lunch in 2011. But the 23 percent is the same as prescribing of all brand drugs in Part D, a percentage that began and continued to decline as more medicines went off patent. We don't know what Avorn and Co.'s data would show in 2012 or 2013 as Lipitor went off patent... We will never know because taking that into account might undermine the conclusion they want to make.
Meanwhile DeJong shows that the undue influence of meals leads to much lower brand utilization in part D than the national market share of each drug.
And here is the trend in brand vs generic over the past decade. And neither study took the time to control for this critical variable?
Finally, neither study tested the reverse assumption: that the biggest prescribers of brand drugs were more likely to have drug reps visit their office, provide samples and schmooze than those that prescribe generic. If they had done that, both groups of authors could have controlled for patent expirations, co-pay effects, etc. that are more highly correlated with prescribing and generic uptake than snacks.
But that wouldn’t fit JAMA's distorted narrative of unscrupulous drug companies seducing dumb doctors with free lunches.
The articles reinforce the assumption that doctors are influenced to prescribe more expensive brand drugs. There is has never been any causal evidence of any sort to support this claim, just anecdotes and the torturing of data that is conducted to fit the narrative.
But let’s say for the sake of argument that the more freebies and lunches doctors received is directly associated with more brand prescribing or specific prescribing of brands. Indeed, that is the hypothesis these two articles seek to test. Except that now, as opposed to even 10 years ago, the amount spent on pharma freebies like lunches and trips worth about $150 has declined. And the number of doctors who get them has fallen too for a number of reasons. At the same time brand prescribing has declined. So the reduction in payments has led to less brand prescribing right?
In Association of Industry Payments to Physicians With the Prescribing of Brand-name Statins in Massachusetts James S. Yeh, MD, MPH; Jessica M. Franklin, PhD; Jerry Avorn, MD; Joan Landon, MPH; Aaron S. Kesselheim, MD, JD, MPH (which I will refer to as Avorn and Co.) claim:
“Industry payments to physicians are associated with higher rates of prescribing brand-name statins. As the United States seeks to reign in the costs of prescription drugs and make them less expensive for patients, our findings are concerning.”
In Pharmaceutical Industry–Sponsored Meals and Physician Prescribing Patterns for Medicare Beneficiaries Colette DeJong, BA concluded:
“Receipt of industry-sponsored meals was associated with an increased rate of prescribing the brand-name medication that was being promoted. The findings represent an association, not a cause-and-effect relationship.”
Dejong and company looked at four specific drugs in different therapeutic class. They note that Crestor was 8.8% statin prescriptions; Benicar 3.3% beta-blocker prescriptions; Benicar was 1.6% of ACE inhibitor and ARB prescriptions; and Prestiq was 0.6% of SSRI and SNRI prescriptions and like Avorn and Co. conclude that prescribing rate was influenced by drug reps passing out donuts and Chipotle.
Except that in both ‘studies’ the brand prescribing rates were BELOW national averages for Medicare part D
The Medicare Payment Advisory Commission reported that
“Generic drugs accounted for 81 percent of all prescriptions filled in 2012 compared with 77 percent and 61 percent in 2011 and 2007, respectively. In 2015, generic fill rate increased again but as Express Scripts Drug Trend Report notes, the fill rates differed by plan type, with Medicare Advantage and stand-alone Part D plans with similar generic fill rates (87.5% and 87.2%, respectively), and Employer Group Waiver Plans with the lowest generic fill rate (82.4%).”
The Avorn group estimated that doctors who got lunch prescribed brand name statins 23 percent of the time vs 18 percent that were deprived of a free lunch in 2011. But the 23 percent is the same as prescribing of all brand drugs in Part D, a percentage that began and continued to decline as more medicines went off patent. We don't know what Avorn and Co.'s data would show in 2012 or 2013 as Lipitor went off patent... We will never know because taking that into account might undermine the conclusion they want to make.
Meanwhile DeJong shows that the undue influence of meals leads to much lower brand utilization in part D than the national market share of each drug.
And here is the trend in brand vs generic over the past decade. And neither study took the time to control for this critical variable?
Finally, neither study tested the reverse assumption: that the biggest prescribers of brand drugs were more likely to have drug reps visit their office, provide samples and schmooze than those that prescribe generic. If they had done that, both groups of authors could have controlled for patent expirations, co-pay effects, etc. that are more highly correlated with prescribing and generic uptake than snacks.
But that wouldn’t fit JAMA's distorted narrative of unscrupulous drug companies seducing dumb doctors with free lunches.
The road to Hell is paved with good intentions -- and often hidden agendas.
Generic drug manufacturers have complained that innovative pharmaceutical manufacturers use FDA-mandated safety-based distribution requirements—called “risk evaluation and mitigation strategies” (REMS)—to prevent or delay generic medicines from coming to market. Some generic and biosimilar manufacturers have argued that innovative manufacturers use REMS to avoid selling samples of their medicines to competitors, which results in some generic and biosimilar manufacturers being unable to complete the testing necessary to obtain FDA approval of their medicines.
To address this issue, generic and biosimilar manufacturers are supporting, the “Creating and Restoring Equal Access to Equivalent Samples Act of 2016” or the “CREATES Act.” The CREATES Act allows a generic or biosimilar manufacturer to bring a civil action in federal court against an innovator to obtain injunctive relief and monetary damages in two instances: (1) where the innovator has failed to provide samples of a drug or biological product within 31 days of a request for samples, and (2) if the companies fail to reach an agreement on the development of a single, shared REMS system. While seeking to address a narrow issue, the bill is drafted in manner that will put patients and medical researchers at risk of serious harm and generate significant and meritless litigation costs for innovative pharmaceutical manufacturers.
Specifically:
The CREATES Act Lacks Adequate Patient Safety Protections
* The CREATES Act fails to adequately protect both patients and medical researchers who participate in clinical trials of REMS drugs conducted by generic or biosimilar manufacturers. This is concerning because REMS drugs are not typical prescription medicines—they are a special class of potentially harmful drugs that may be subject to restrictions called “elements to assure safe use” (ETASU), which FDA deems as necessary to ensure patient safety. In fact, many REMS drugs subject to ETASU may only be distributed with specific safeguards to protect anyone who comes in contact with the medicine.
* The bill fails to ensure sufficient FDA oversight of safety protections for subjects and researchers in studies of drugs having REMS with ETASU. To obtain an authorization, a generic or biosimilar manufacturer may -- but need not -- submit a clinical trial safety protocol outlining its planned testing of the drug in patients. The bill does not require FDA to pre-approve the safety protocol or to even make the determination that it provides equivalent protections for patients and researchers in comparison with the REMS with ETASU. The bill also grants FDA no authority to suspend a generic or biosimilar manufacturer’s access to samples or otherwise modify or revoke an authorization if the generic or biosimilar manufacturer does not implement appropriate safeguards.
* Instead of providing the FDA with authority to address these safety issues, the bill tasks the federal courts with adjudicating the terms. Although the bill contemplates a limited role for FDA in the authorization process for these products, the federal courts will determine what, if any, safety protections imposed on the transfer of samples are reasonable. The federal courts lack the expertise of FDA in evaluating the safety of a medicine and the measures necessary to protect patients and researchers.
The CREATES Act Exposes Innovative Manufacturers to Liability Risks Through No Fault of Their Own
* The CREATES Act will hold innovators responsible for the actions of generic and biosimilar manufacturers because the bill provides innovators liability protection only for claims arising out of failure to follow adequate safeguards during handling or use of product by the generic or biosimilar manufacturer. As a result, innovative manufacturers could still be unfairly liable for others’ negligence, long after the medicine has left their control. The CREATES Act exposes innovators to significant new liability risks based on the actions of their competitors.
The CREATES Act Hurts Patient Access to Life Sustaining Therapies During Drug Shortages
* The CREATES Act could exacerbate drug shortages and further limit the supply of medically necessary drugs. If a medicine has been on the shortage list for more than six months, the medicine is not exempt from the bill. In other words, manufacturers of these products would be forced to divert medicines from their patients—even when the medicines are life sustaining—to ensure supply for their competitors’ clinical trials.
More careful consideration needs to be inserted into the CREATES Act design so that it more clearly addressed its intent and avoids unintended consequences or hidden agendas. Patient safety, public health, and healthcare innovation mustn't become innocent victims.
Generic drug manufacturers have complained that innovative pharmaceutical manufacturers use FDA-mandated safety-based distribution requirements—called “risk evaluation and mitigation strategies” (REMS)—to prevent or delay generic medicines from coming to market. Some generic and biosimilar manufacturers have argued that innovative manufacturers use REMS to avoid selling samples of their medicines to competitors, which results in some generic and biosimilar manufacturers being unable to complete the testing necessary to obtain FDA approval of their medicines.
To address this issue, generic and biosimilar manufacturers are supporting, the “Creating and Restoring Equal Access to Equivalent Samples Act of 2016” or the “CREATES Act.” The CREATES Act allows a generic or biosimilar manufacturer to bring a civil action in federal court against an innovator to obtain injunctive relief and monetary damages in two instances: (1) where the innovator has failed to provide samples of a drug or biological product within 31 days of a request for samples, and (2) if the companies fail to reach an agreement on the development of a single, shared REMS system. While seeking to address a narrow issue, the bill is drafted in manner that will put patients and medical researchers at risk of serious harm and generate significant and meritless litigation costs for innovative pharmaceutical manufacturers.
Specifically:
The CREATES Act Lacks Adequate Patient Safety Protections
* The CREATES Act fails to adequately protect both patients and medical researchers who participate in clinical trials of REMS drugs conducted by generic or biosimilar manufacturers. This is concerning because REMS drugs are not typical prescription medicines—they are a special class of potentially harmful drugs that may be subject to restrictions called “elements to assure safe use” (ETASU), which FDA deems as necessary to ensure patient safety. In fact, many REMS drugs subject to ETASU may only be distributed with specific safeguards to protect anyone who comes in contact with the medicine.
* The bill fails to ensure sufficient FDA oversight of safety protections for subjects and researchers in studies of drugs having REMS with ETASU. To obtain an authorization, a generic or biosimilar manufacturer may -- but need not -- submit a clinical trial safety protocol outlining its planned testing of the drug in patients. The bill does not require FDA to pre-approve the safety protocol or to even make the determination that it provides equivalent protections for patients and researchers in comparison with the REMS with ETASU. The bill also grants FDA no authority to suspend a generic or biosimilar manufacturer’s access to samples or otherwise modify or revoke an authorization if the generic or biosimilar manufacturer does not implement appropriate safeguards.
* Instead of providing the FDA with authority to address these safety issues, the bill tasks the federal courts with adjudicating the terms. Although the bill contemplates a limited role for FDA in the authorization process for these products, the federal courts will determine what, if any, safety protections imposed on the transfer of samples are reasonable. The federal courts lack the expertise of FDA in evaluating the safety of a medicine and the measures necessary to protect patients and researchers.
The CREATES Act Exposes Innovative Manufacturers to Liability Risks Through No Fault of Their Own
* The CREATES Act will hold innovators responsible for the actions of generic and biosimilar manufacturers because the bill provides innovators liability protection only for claims arising out of failure to follow adequate safeguards during handling or use of product by the generic or biosimilar manufacturer. As a result, innovative manufacturers could still be unfairly liable for others’ negligence, long after the medicine has left their control. The CREATES Act exposes innovators to significant new liability risks based on the actions of their competitors.
The CREATES Act Hurts Patient Access to Life Sustaining Therapies During Drug Shortages
* The CREATES Act could exacerbate drug shortages and further limit the supply of medically necessary drugs. If a medicine has been on the shortage list for more than six months, the medicine is not exempt from the bill. In other words, manufacturers of these products would be forced to divert medicines from their patients—even when the medicines are life sustaining—to ensure supply for their competitors’ clinical trials.
More careful consideration needs to be inserted into the CREATES Act design so that it more clearly addressed its intent and avoids unintended consequences or hidden agendas. Patient safety, public health, and healthcare innovation mustn't become innocent victims.
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.
