Latest Drugwonks' Blog
The Washington Post reports Capital City Care dispensary sold Washington DC’s first legal marijuana “in at least 75 years” on Monday. The sale is a result of a “15-year struggle to legalize medical marijuana in the district,” the culmination of a battle that “dates to the mid-1990s, when HIV/AIDS activists first fought to put medical marijuana on the citywide ballot.” About 70% of DC voters approved a 1998 legalization initiative, only to have it squashed by Congress for over a decade. But after Congress lifted the restriction in 2009, it still took several years for the city government to establish a “strict regulatory and licensing regime limited to city residents with specific chronic illnesses,” while also minimizing the “risk of future federal intervention.”
The New England Health Institute has released a new report calling on public and private policymakers to adopt six “priorities for action” to improve the way patients take their prescription medicines across the US.
NEHI has created six “priorities for action” to improve the way patients take their prescription medicines across the US. They are:
1) Promote sharing of best practices and lessons learned from pilots of new medication management techniques
2) Support large-scale implementation of promising, evidence-based “tactics” for improved medication management
3) Continue development of metrics of medication use that will spur adoption of proven medication management strategies
4) Support continued rapid adoption of electronic prescribing and electronic medical records with capabilities that support evidence-based interventions for improved adherence
5) Continue to improve Medication Therapy Management services in Medicare Part D including improvements in program services and targeting; consider wider adoption of medication management by other health care payers
6) Integrate medication adherence research, policy development and advocacy with broader efforts that aim to improve use of medicines, including those focused on patient safety
The report concludes:
Proponents of better patient adherence should rally behind a comprehensive vision of good medication use that encompasses interventions to promote adherence, and promote a vigorous agenda for policy change that will create incentives for proven adherence interventions.
Words to the wise.
One major problem is the so-called Independent Payment Advisory Board. The IPAB is essentially a health-care rationing body. By setting doctor reimbursement rates for Medicare and determining which procedures and drugs will be covered and at what price, the IPAB will be able to stop certain treatments its members do not favor by simply setting rates to levels where no doctor or hospital will perform them.
There does have to be control of costs in our health-care system. However, rate setting—the essential mechanism of the IPAB—has a 40-year track record of failure. What ends up happening in these schemes (which many states including my home state of Vermont have implemented with virtually no long-term effect on costs) is that patients and physicians get aggravated because bureaucrats in either the private or public sector are making medical decisions without knowing the patients. Most important, once again, these kinds of schemes do not control costs. The medical system simply becomes more bureaucratic.
The nonpartisan Congressional Budget Office has indicated that the IPAB, in its current form, won't save a single dime before 2021. As everyone in Washington knows, but less frequently admits, CBO projections of any kind—past five years or so—are really just speculation. I believe the IPAB will never control costs based on the long record of previous attempts in many of the states, including my own state of Vermont.
Read the full piece in the Wall Street Journal.
Speaking of clinical trial data transparency – here’s an excellent analysis from the August edition of the Burrill Report ...
Fight for Transparency Heats Up: Industry turns to courts to stop policy in EU, offers own approach
Daniel S. Levine
Tom Jefferson had nagging concerns about his review for the Cochrane Collaboration of clinical studies of the flu drug Tamiflu, but they crystallized in 2009 when a Japanese pediatrician raised a question about the work via email. The doctor wanted to know why the review included eight unpublished trials that Jefferson and his colleagues hadn’t seen, and had only been included as summaries in another study funded by the drug’s producer Roche?
The solution seemed simple enough. Jefferson, an epidemiologist based in Rome who was conducting the updated analysis for the Cochrane Collaboration, an independent group that provides guidance to healthcare professionals on the use of drugs, would reach out to the authors of the studies and get them. But the authors either told him they didn’t have the data, said they had never seen the data, or ignored him completely. When he asked Roche for the studies, it said it would provide them, but insisted at first that he sign a confidentiality agreement, a condition that he found unacceptable.
The controversy came against a backdrop of worldwide fear of a global pandemic of bird flu that sent the World Health Organization, the Centers for Disease Control and Prevention, and governments around the world spending billions of dollars to stockpile Tamiflu. Despite the spending, Jefferson says there were questions about whether the drug did anything to prevent transmission of flu, minimize complications, or whether the health benefits the drug provided justified the risks of using it. Roche, in a statement posted on its web site and updated at the end of February 2013, said that it had disagreed with the analysis plan Cochrane Collaboration shared with it because it was at odds with how Tamiflu has been reviewed and approved by regulatory authorities in more than 80 countries. The company said it stood by the “robustness and integrity” of its data supporting the safety and efficacy of the drug.
“The fight for the last four years hasn’t been so much for clinical study reports,” Jefferson says, “but to have clinical study reports without having to sign confidentiality agreements, funny handshakes, rolling up our trouser leg, and so on.”
The four-year battle to obtain clinical trials data—he believes that there have been 123 studies (74 of which Roche sponsored)—has made Jefferson a flag bearer in an international fight over clinical trials data transparency. The controversy, which is by no means limited to Tamiflu and Roche, is now reaching a critical point. A legal battle is underway in Europe over a European Medicines Agency transparency policy expected to take effect at the start of 2014 that would make public clinical trial data once a drug is approved. At the same time, in the United States, the Institute of Medicine is at work on a consensus study on the issue and the U.S. Food and Drug Administration is seeking comment on a clinical data transparency policy of its own.
Much is at stake as the policymakers embrace comparative effectiveness and the advent of Big Data provides a new means to ferret out untapped information hidden within clinical study reports—the detailed narrative reports at the individual patient level that can run to tens of thousands of pages in a single trial.
Proponents of clinical data transparency argue that it will provide doctors with greater insight into the safety and efficacy of the drugs they prescribe, improve care, cut waste, and minimize scientific misconduct and fraud. Peter Doshi, a post doctoral comparative effectiveness researcher at Johns Hopkins University, who is also working on the Tamiflu review for the Cochrane Collaboration, points to a list of blockbuster drugs that were marketed only to have significant health risks come to light through academicians analyzing clinical trials data. “The whole system has depended on trust in medicine, trust in people to report properly, trust in people to have enough information to credibly analyze trials,” he says. “We know enough not to be so trusting anymore.”
Industry, while not of one mind, says that in principle it doesn’t oppose transparency, but expresses concerns about how it is done. These concerns include the threat to confidential commercial information, the challenge to the authority of regulators, the risk to patient privacy, and the opening of the data to inappropriate uses that could lead to the publication of misleading results and public health scares.
Lawsuits in Europe
In May, the General Court of the European Union prohibited the European Medicines Agency from releasing data from two AbbVie and Intermune trials in an interim ruling, part of a challenge by the two drugmakers to the agency’s decision to grant access to information the companies provided as part of their market approval applications. The challenge is the first to be made to the EMA’s three-year old access-to-documents policy.
Since November 2010, the Agency has released more than 1.9 million pages in response to such requests. The legal battle involves documents relating to AbbVie’s rheumatoid arthritis drug Humira and InterMune’s Esbriet, a treatment for idiopathic pulmonary fibrosis, an unexplained chronic and progressive scarring of the lungs. In both cases, competitors of the companies were seeking the data.
“Biopharmaceutical companies support responsible data sharing that protects patient privacy, maintains the integrity of the regulatory review process, and preserves incentives for biomedical research,” said Matt Bennett, senior vice president for the Pharmaceutical Research and Manufacturers of America in a statement at the time. “Unfortunately, the EMA’s current and proposed policies fail to respect these principles.”
The ruling comes amid increasing pressure from medical journals and patient advocates on pharmaceutical companies to provide complete transparency and make public all of their clinical trials data. It also comes as the EMA readies implementation of a new policy to proactively publish data from clinical trials supporting the approval of new drugs once a decision has been made. The EMA said it would continue the process of drafting its policy on publication of clinical trials data.
Ben Goldacre, author of “Bad Pharma” and co-founder of the AllTrials campaign, which seeks publication of all results from all clinical trials, called the ruling “a disgrace.” “There is no justification for withholding information about the methods and results of clinical trials from doctors, researchers, payers and patients, who need all the information on a medicine to make truly informed decisions,” he says.
The EMA says it welcomes the opportunity for legal clarification of the concept of commercially confidential information, but expressed “regret” over the decision to grant interim relief to AbbVie and InterMune.
FDA, IOM, weigh transparency
In the United States, although efforts to bring about transparency have moved slower, they are advancing. In October 2012, the Institute of Medicine held a two-day workshop to explore the benefits of sharing clinical research data, the issues surrounding it, and how best to do so. The IOM is now working on a consensus study that some hope could provide a roadmap for the development of a clinical trials data transparency policy in the United States.
A group of leading pharmaceutical and biotechnology companies has been involved in the IOM process and issued a press release hailing the effort. “This industry group is strongly in support of enhanced access by third party research to clinical trial data generated by industry and academia in a manner that ensures that patient confidentiality is preserved, scientific integrity is maintained, and intellectual property rights and confidential company information are protected,” they said in a joint statement.
The Food and Drug Administration is seeking public comments through August 5 on a policy to make available de-identified and masked data derived from medical product applications. But advocates of transparency say such data will be of limited utility because the policy under consideration would de-identify it and remove the data’s link to a specific product, study, or application.
Peter Pitts, president of the Center for Medicine in the Public Interest and chairman of a conference on clinical trials data transparency held by FDANews July 23-24, says it’s “a non-arguable fact that FDA is at the nexus of vast amounts of clinical data that if it was appropriately shared it would be of tremendous value.” He says that sharing information, among other things, could help companies fail faster, which would save a lot of money and allow for reinvestment of diminishing resources. But such an effort, he says would require information technology resources the agency is without, decisions on what is and isn’t redacted, discussions about intellectual property rights and commercial confidentiality, and funding for it all.
“We’ve come to the point now, relative to clinical trials data, that transparency is a good thing. The question now becomes, ‘How do you accomplish that and what exactly does transparency mean? And how quickly does it become transparent? And how much of it becomes transparent and how much of it remains confidential? Is it transparent through corporate entities, or is it transparent through a consortium of corporations? Is it transparent through a government organization? And who ultimately decides? Can people opt out? And if people opt out, can you really have transparency?’” says Pitts. “They are all very tough questions.”
(Note: For more on the FDA News conference, see Cry “havoc,” and let slip the dogs of data transparency.
Progress, but no victory
Four years after Jefferson began his efforts to access clinical study reports from Roche and GlaxoSmithKline, which produces the Tamiflu competitor Relenza, both of which are in the class of drugs known as neuraminidase inhibitors, it is Roche and GSK that arguably have the clearest defined and most advanced efforts to provide clinical trials data to outsiders.
Roche has complied with the original request the Cochrane reviewers made in 2009, although the researchers continue to pursue access to additional trials data of which they subsequently learned. The Cochrane Collaboration expects at the start of 2014 to publish a new review of neuraminidase inhibitors based on 23 clinical studies on Relenza and up to 20 studies on Tamiflu.
In February, GSK announced it had signed on in support of the AllTrials campaign and has vowed to publish clinical trials data of all approved drugs dating back to 2000, the date the company was formed through the merger of Glaxo Wellcome and SmithKline Beecham.
“We are committed to being transparent with our clinical trial data to help advance scientific understanding and inform medical judgment,” Patrick Vallance, President, Pharmaceuticals R&D, GlaxoSmithKline, said in announcing support for the campaign. “Our commitment also acknowledges the very great contribution made by the individuals who participate in clinical research. All those involved in the conduct and publication of clinical research, whether healthcare companies like GSK, academia or research organizations, have a role to play in ensuring that the data they generate are made publicly available to help bring patient benefit.”
In response to questions from The Burrill Report, GSK said it believes a broader solution for providing access to trial data from across the research community needs to be developed and it has been in discussion with trials sponsors from industry, academia, and research charities working in partnership to create one. GSK says one solution would be the establishment of an independent data custodian to which research sponsors would deposit anonimized data after a project has been completed and clinical studies are published. Researchers could then submit scientific proposals and analysis plans to independent custodian to request access.
The Pharmaceutical Research and Manufacturers of America and the European Federation of Pharmaceutical Industries and Associations at the end of July jointly issued a list of principles for clinical trial data sharing. They call for a voluntary plan that would make data available to only to “qualified” researchers who sign non-disclosure agreements. They say they would only share data for which they have the informed consent of study participants to do so.
(Note: The full principles can be found on the PhRMA website. PhRMA said implementation of the commitments in the principles will begin on January 1, 2014.)
Companies will start reviewing requests for data from researchers at that point, but Castellani said companies will need to take into account patients’ informed consent. He said it will not be possible to share data from many earlier trials because patients participating in them did not consent to such release.)
But advocates worry that the victories in studies extracted from pharmaceutical companies to date may be short lived, in large part due to the legal battle in Europe over the EMA’s transparency policy. “Societal expectations have dramatically moved in a direction of greater transparency, but there remain serious risks to the process that could potentially derail a lot of the progress that has been made,” says Johns Hopkin’s Doshi. “The progress we’ve seen with Tamiflu may have been a one-off victory for what otherwise may be a return of data secrecy. Many people think the goals of transparency have been achieved, but they have not.”
ANOTHER DAY, ANOTHER POLLING NADIR FOR OBAMACARE - This time, the bad news for the White House came from CBS, which found that 39 percent of respondents want the law wiped from the books, the highest percentage since the broadcaster began asking the question. That's compared to 36 percent who want to keep or expand the law. Recent polls have tended to show the law mired in continued uncertainty and unpopularity among Americans, a dynamic supporters hope will start to shift once the key benefits of the law come online in January.
Yesterday I had the privilege to chair the Clinical Trials Disclosure and Transparency Summit.
Here are my opening remarks:
Simplistic solutions to important public health issues are generally wrong, often deleterious to the issue at hand --and often hide political versus public health agendas. Or as Henry Kissinger once said:
”The real distinction is between those who adapt their purposes to reality and those who seek to mold reality in the light of their purposes.”
And so, with that introduction, welcome to the Clinical Trial Disclosure and Transparency Summit.
In a recent op-ed in the New York Times, biasedly titled, Health Care’s Trick Coin, Ben Goldacre (the author of the neutrally titled book, Bad Pharma: How Drug Companies Mislead Doctors and Harm Patients, made a number of serious allegations – and factual mistakes in his discussion of clinical trial transparency – specifically that the Clinicaltrials.gov registration requirement in FDAAA isn't being implemented and that only “full transparency and publication of clinical trial will address the issue.” It’s not so simple – and the facts matter.
As the former senior government official in charge of clinicaltrials.gov, it’s important to look at the facts – and the numbers.
In 2000, the National Institutes of Health (NIH) launched ClinicalTrials.gov to provide public access to information on clinical studies. Although it initially contained information primarily on NIH-funded research, it has been expanded to include both publicly and privately supported clinical research.
Since the launch of the site, it has been enhanced to significantly increase data sharing. The ClinicalTrials.gov database includes information on nearly 140,000 clinical trials in all 50 states and 182 countries.
Is anyone accessing this wealth of information? Yes! The NIH reported last year that ClinicalTrials.gov “receives more than 95 million page views per month and 60,000 unique visitors daily.
Facts do not cease to exist because they are ignored. Mr. Goldacre should realize that reality, although sometimes inconvenient to ones argument, remains reality.
As we progress through the next two days, here are some issues we will consider:
· The FDA is at the nexus of vast amounts of patient-level clinical data – what role will transparency play in making such information available? How might the agency accomplish such a task, how would it be funded – and where does such an initiative fall on the agency’s long list of urgent priorities?
· How will current AbbVie/Intermune legal decision in the EU impact transparency issues here at home?
· How will the IOM report impact how we view transparency going forward? Indeed – how will the IOM move forward on this issue – or will it?
· Should transparency be a government dictate or a working collaboration between interested parties both private and public – and what role should patients play. Should there be formalized transparency consortia? Should it be global?
· What are the implications for intellectual property and the connected question of incentivizing (or dis-incentivizing) investment in innovation? Is transparency a Trojan horse to attack patents and intellectual property rights?
· How can we avoid making transparency a game of “gotcha” such as what happened at the 2010 Avandia hearing where a grandstanding Henry Waxman pointed his finger at the GSK research chief and stridently said, “do you swear under oath that you will make all clinical trial data available? Only to get the embarrassing response, “Congressman, it’s available right now at www.gsk.com.”
· What about the availability of data from unpublished negative trials? Why aren’t payers asking for these before they make reimbursement decisions? For those of you following the debate over FDAMA 114 and the use of pharmaco-economic data for reimbursement decisions, this shouldn’t be an unfamiliar discussion. Can a free-market solutions drive transparency?
· Can transparency become a competitive advantage as well as a public health imperative?
After all, good things happen when everybody wins.
Ladies and Gentlemen – start your engines.
The Summit’s first speaker was Dr. Richard Moscicki, CDER’s new Deputy Director for Science Operations. His presentation focused on the transparency dichotomy of “the promise versus fear and loathing.”
As to “why” transparency, he offered reproducibility, re-analysis the potential to identify new information (placebo effects, biomarkers, endpoints, trial designs).
And then his talk got interesting. He laid it on the table that one group that is silently against transparency is academics – because they don’t want to be cornered into making studies public if it impacts their ability to publish.
The FDA’s impediments to data sharing, according to Moscicki are (1) Legal (data ownership, HIPAA/privacy, proprietary information), (2) technical/practical (format, data standards, CDISC, redaction), (3) Resources and, (4) the agency’s need to focus on its key mission.
Per that last point, he honestly shared that the FDA does not view (at least at as of right now) the issue of clinical trial data transparency as a key agency agenda item – unless there was move to move it to the head of the regulatory queue via user fees. (That would be DTUFA – Data Transparency User Fee Act. Folks – you heard it here first.)
But transparency is important and, per Moscicki, “inevitable” – and to that end he discussed the agency’s recent Federal Register Notice (Masked and De-identified Non-Summary Safety and Efficacy Data).
FDA invites comments on the issues it should consider with respect to the availability of clinical and pre-clinical study data after steps have been taken to “de-identify” it by removing any personally identifiable information and “mask” it by removing data that could link it to a specific application or sponsor. Specifically, the agency is interested in comments from the public on the following topics:
– What factors should be considered in masking study data (e.g. should certain data fields be removed or modified; number of different products to pool within a class)?
– Should there be any limitations on the agency’s ability to make masked data available?
– In addition to current FDA requirements to remove any names and other information that might identify patients, what other information should FDA consider when de-identifying the data?
– Would regulatory changes facilitate the implementation of this proposal?
– In what situations would disclosing masked data be most useful to advance public health?
Moscicki stressed that FDA’s approach has been under development for several years and
* It is not linked to EMA proposal;
* FDA is not contemplating routine preparation and release of de-identified and masked clinical and non-clinical study data;
* The agency is encouraging independently organized efforts to create, curate and share clinical trial datasets from all sources.
Dr. Moscicki’s complete PowerPoint presentation can be found here.
Next up on the agenda was Sir Alasdair Breckenridge, former Chairman of the MHRA and currently the Chair of United Kingdom’s Department of Health Emerging Science and Bioethics Advisory Committee.
Sir A. challenged the assemblage with the statement that transparency is “a process without a beginning or an end. It is a continuum.” And, “Transparency is like feeding a hungry dog – you more you give it, the more it wants.”
Cry havoc – and let slip the dogs of data transparency.
His presentation focused on four key questions:
(1) Should the public have access to data on which regulatory decisions are taken?
(2) What are the advantages and disadvantages of increased transparency?
(3) What are the key distinctions between transparency and communication (specifically the issue of public health literacy and numeracy – and the “road testing” of released information)?
(4) Will increased transparency lead to increased trust in regulators and industry?
On that last point, Dr. Breckenridge pointed out at increased transparency does not lead to increased trust. Trust depends on perceptions of honesty and competence, and transparency may expose inherent inefficiencies in a system. And that’s a good thing – if we really mean to make the most of transparency.
Transparency cannot be “for thee but not for me.”
He offered five keystones for moving forward:
(1) Agreement on timing of release of information
(2) Agreement on nature of information to be released
(3) Standards of protection of personalized data
(4) Standards for meta-analyses
(5) Rules of engagement for observational studies
He also discussed the EMA’s mad dash towards data transparency and the severe blow it was dealt by the legal victory of AbbVie and Intermune. A lesson that should be noted by the Ben Goldacres's of the world -- and the British Medical Journal.
Sir Alasdair’s PowerPoint presentation can be found here.
Maybe the FDA’s incremental and collaborative approach is best after all. Slow and steady ain’t sexy – but it generally works best -- and is in the best interest of the public health.
According to a report in the Pink Sheet, “Spurred by increasing stakeholder requests for clarity, FDA may be moving toward developing guidance on how and when drug firms can provide health care economic data to formulary managers.”
Per an FDA spokesperson “This is one of the areas that is of interest to FDA and we are discussing possible guidance development.”
The guidance could help clarify the regulatory parameters around the provision in the FDA Modernization Act of 1997 that allows drug companies to proactively disseminate health care economic information to formulary committees within certain limitations. Sec. 114 requires that such information be supported by “competent and reliable scientific evidence” and that any health economic information disseminated must “directly relate” to a drug’s approved indication.
As payers push for more information on the cost effectiveness of drug treatment, manufacturers are taking a closer look at Sec. 114 and are seeking direction from the agency on how it could be used. FDA Office of Prescription Drug Promotion Director Tom Abrams recently acknowledged heightened stakeholder interest in guidance on appropriate communications under FDAMA Sec. 114. “We know that’s a hot topic – what goes to formulary committees and similar bodies,” he said on June 25at the DIA annual meeting in Boston.
Abrams identified dissemination of health care economic information as one of four topics the agency is “exploring for future guidance development.” The other three are medical practice guidelines, comparative claims and “scientific exchange.”
Abrams’ DIA remarks are the first inkling of Agency movement since late 2011 when, according to a notice in the Federal Register:
The Food and Drug Administration (FDA) is announcing the establishment of a docket to assist with our evaluation of our policies on communications and activities related to off-label uses of marketed products, as well as communications and activities related to use of products that are not yet legally marketed for any use, we would like to obtain comments and information related to scientific exchange. FDA is interested in obtaining comments and information regarding scientific exchange about both unapproved new uses of products already legally marketed (“off-label” use) and use of products not yet legally marketed for any use.
And the issue of “scientific exchange” comes front and center. According to the FR notice, To assist with our evaluation of our policies on communications and activities related to off-label uses of marketed products, as well as communications and activities related to use of products that are not yet legally marketed for any use, we would like to obtain comments and information related to scientific exchange.
The FR notice puts this request into perspective:
On July 5, 2011, a citizen petition was submitted by Ropes & Gray and Sidley Austin LLP on behalf of seven product manufacturers (Petitioners): Allergan, Inc.; Eli Lilly and Co.; Johnson & Johnson; Novartis Pharmaceuticals Corp.; Novo Nordisk, Inc.; Pfizer, Inc.; and sanofi-aventis U.S. LLC under 21 CFR 10.30. The citizen petition requested that FDA clarify its policies for drug products and devices governing certain communications and activities related to off-label uses of marketed products and use of products that are not yet legally marketed for any use. Specifically, the petition requests clarification in the following areas:
1. Manufacturer responses to unsolicited requests;
2. Scientific exchange;
3. Interactions with formulary committees, payers, and similar entities; and
4. Dissemination of third-party clinical practice guidelines.
For some time, FDA has been considering these issues and is currently evaluating our policies on sponsor or investigator communications and activities related to off-label uses of marketed products and use of products that are not yet legally marketed for any use. We have been considering what actions to take in the areas specified by the petitioners with respect to manufacturer responses to unsolicited requests; interactions with formulary committees, payors, and similar entities; and the dissemination of third-party clinical practice guidelines.
Specifically, the FDA asks:
• How should FDA define scientific exchange?
• What types of activities fall under scientific exchange?
• What types of activities do not fall under scientific exchange?
• Are there particular types and quality of data that may indicate that an activity is, or is not, scientific exchange?
• In what types of forums does scientific exchange typically occur? Should the use of certain forums be given particular significance in determining whether an activity is scientific exchange or an activity that promotes the drug or device? If so, which forums?
• What are the distinctions between scientific exchange and promotion? What are the boundaries between scientific exchange and promotion?
• Generally, who are the speakers involved in scientific exchange, and who is the audience for their communications?
• Should the identity of the participants (either speakers or audience) be given particular significance in determining whether an activity is scientific exchange or an activity that promotes the drug or device? If so, which participants would be indicative of scientific exchange and which would be indicative of promotion?
• How do companies generally separate scientific roles and promotional roles within their corporate structures?
• How should the Agency treat scientific exchange concerning off-label uses of already approved drugs and new uses of legally marketed devices? Please address whether there should be any distinctions between communications regarding uses under FDA-regulated investigation (to support potential approval) and communications regarding uses that are not under express FDA-regulated investigation.
• How should the Agency treat scientific exchange concerning use of products that are not yet legally marketed (that is, products that cannot be legally distributed for any use outside of an FDA- or institutional review board (IRB)-approved clinical trial)?
• Should investigational new drugs and investigational devices be treated the same with respect to scientific exchange? Why or why not?
• Under 21 CFR 812.7(b), an investigational device is considered to be “commercialized” if the price charged for it is more than is necessary to recover the costs of manufacture, research, development, and handling. Similarly, FDA considers charging a price for an investigational drug that exceeds that permitted under its regulations (generally limited to cost recovery) to constitute “commercialization” of the drug (see 74 FR 40872 at 40890, August 13, 2009; 52 FR 19466 at 19467). What other actions indicate the commercialization of drug and/or device products? If there are differences in the steps taken to commercialize drug products and the steps taken to commercialize device products, either before or after approval, please explain these differences.
A lot of questions and, it seems, a lot of potential regulatory mission creep.
Relative to, “Interactions with formulary committees, payors, and similar entities,” the door is now also open for debate on FDAMA Section 114 and health economic data.
There is no on-the-books draft or final guidance on Section 114. It’s been 14 years since the initial language. Health-related quality of life claims are considered under the established "adequate and well-controlled trials" standard.
Some background to put this into perspective:
To address concerns that FDA regulations were limiting the dissemination of outcomes research, Congress added Section 114 to set a new, less stringent standard applicable to promotional dissemination of health care economic information to MCO formulary committees: "competent and reliable scientific evidence."
Even though there is no FDA guidance to explain the agency's understanding "competent and reliable scientific evidence,” PhRMA developed a draft guidance, which was submitted to the FDA in June 1998. In its draft, PhRMA sought input from the International Society for Pharmacoeconomics and Outcomes Research, the Society for Medical Decision Making, the Academy of Managed Care Pharmacy, the American Pharmaceutical Association, and other groups.
In its submission to the FDA, PhRMA explained the history behind Section 114 and proposed guidance on the following terms used in the new law:
- Health care economic information.
- Managed care or other similar organizations.
- Formulary committee or other similar entity.
- Directly related to an approved indication.
- Competent and reliable scientific evidence.
The PhRMA proposal took an approach to interpretation consistent with Congress's intent that Section 114 would increase the dissemination of outcomes research information by product manufacturers to MCOs. PhRMA concluded that the term "health care economic information" should include all forms of economic analysis so the guidance could adapt to new and evolving outcomes research methods.
One of the phrases in Section 114 that is difficult to interpret is that promotion must involve a claim that "directly relates to an indication approved [by the FDA]." In the draft guidance, PhRMA proposed that extrapolation from data included on labeling would be appropriate at least under the following circumstances: from duration of use in labeling to actual duration of use found in pharmacy databases, from dosages included in labeling to actual dosages found in pharmacy databases, and from controlled trial settings to actual practice settings.
The standard set by Section 114, "competent and reliable scientific evidence," is the same standard used by the Federal Trade Commission (FTC) when assessing the adequacy of substantiation for manufacturer claims involving OTC drugs and products affecting environmental health. That standard requires transparency of methods and use of methods accepted by experts in the field. In its proposal, PhRMA recommended that the FDA follow long-established FTC interpretation of the competent and reliable scientific evidence standard.
The full FR Notice on "Communications and Activities Related to Off-Label Uses of Marketed Products and Use of Products Not Yet Legally Marketed; Request for Information and Comments" can be found here.
In October 2012, PhRMA issued a white paper, asking the FDA for guidance on the supporting evidence drug companies need for the health care economic data they send to formulary managers should specifically allow for use of a range of data sources, not limited to adequate and well-controlled clinical trials.
The white paper urges the agency to develop formal regulatory guidance on Sec. 114 of the FDA Modernization Act of 1997, which allows drug companies to proactively disseminate health care economic information to formulary committees within certain limitations.
The white paper outlines a number of data elements that should satisfy the competent and reliable scientific evidence standard. They include: methods for establishing economic costs and consequences that are widely accepted by experts in the field using a clear, pre-defined study protocol; an “accurate and balanced assessment of the economic consequences of a drug therapy, consistent with the current weight of credible evidence”; a representative study population; and information that allows the reader to determine how the research was conducted.
PhRMA recommends that FDA allow the competent and reliable standard to be satisfied with data obtained through a number of different methods, including observational study designs, database reviews and other economic modeling techniques. “There should be no pre-specified number or type of study required to substantiate a claim."
For example, “a claim that a drug is more cost-effective than a competing drug may be made where the cost savings are due to reduced resource utilization resulting from improved efficacy outcomes, decreased administration or monitoring costs, or where the difference in cost is due to the drug causing fewer adverse events, as long as these differences are supported by competent and reliable evidence.”
PhRMA argues that FDA should not consider such a statement a comparative clinical claim, which would trigger the “substantial evidence” requirement involving clinical trials.
Companies should be permitted to disseminate data on the “real world” economic implications of a therapy on health outcomes, according to the white paper. For example, “if a manufacturer conducts a competent and reliable study investigating the impact of a drug indicated for the treatment of diabetes mellitus on costs associated with cardiovascular care, the manufacturer should be permitted to proactively disseminate such data to appropriate audiences.”
Tom Abrams’ comments should act as more than a passing notice. Folks – it’s time to step up to the plate – the implications for payers and academic detailing are both timely and significant.
From that well-know Tea Party mouthpiece – the Associated Press …
FACT CHECK: Obama spins health insurance rebates
WASHINGTON (AP) - Another year, another round of exaggeration from President Barack Obama and his administration about health insurance rebates.
In his speech defending his health care law Thursday, Obama said rebates averaging $100 are coming from insurance companies to 8.5 million Americans. In fact, most of the money is going straight to employers who provide health insurance, not to their workers, who benefit indirectly.
Obama danced around that reality in remarks that also blamed problems in establishing affordable insurance markets on political opponents, glossing over complex obstacles also faced in states that support the law.
A look at some of his claims and how they compare with the facts:
-"Last year, millions of Americans opened letters from their insurance companies. But instead of the usual dread that comes from getting a bill, they were pleasantly surprised with a check. In 2012, 13 million rebates went out, in all 50 states. Another 8.5 (million) rebates are being sent out this summer, averaging around 100 bucks each."
- After introducing several people who got rebate checks last year: "And this is happening all across the country. And it's happening because of the Affordable Care Act. Hasn't been reported on a lot. I bet if you took a poll, most folks wouldn't know when that check comes in that this was because of Obamacare that they got this extra money in their pockets. But that's what's happening."
-" If they're (insurers) not spending your premium dollars on your health care - at least 80 percent of it - they've got to give you some money back."
THE FACTS: Just as he did a year ago, Obama made a splashy announcement about rebates that incorporates misleading advertising.
The health care law requires insurance companies that spend too much on administrative expenses to issue rebates to customers. But those customers are often employers that in turn offer insurance to workers and bear the bulk of the costs. In workplace plans, the rebate goes to the employer, which must use it for the company health plan but does not have to pass all or part of it on to the worker. People who buy their own insurance and qualify for a rebate get it directly.
Obama was on solid ground in saying "millions of Americans" got rebate checks last year, but the number was not close to 13 million as he implied.
Of the 12.8 million rebates announced last year, health policy experts estimated 3 million would go directly to the insured. The government didn't know how many.
Nearly two-thirds of the 12.8 million were only entitled to pro-rated and decidedly modest rebates, because they were covered by employers that pay most of their premiums. Workers typically pay about 20 percent of the premium for single coverage, 30 percent for a family plan. Employers pay the rest.
And employers can use all the rebate money, including the workers' share, to benefit the company health plan, perhaps restraining premiums a bit or otherwise improving the bottom line. The law requires insurers to spend at least 80 percent of premiums they collect on medical care and quality improvement, or return the difference to consumers and employers.
Altogether, this year's rebates are worth $500 million, down from $1.1 billion returned last year. The government says the lower rebates mean insurance companies are becoming more efficient.
-"I'm curious, what do opponents of this law think the folks here today should do with the money they were reimbursed? Should they send it back to the insurance companies?"
THE FACTS: Even in that unlikely event, most people could not send it back to insurance companies because the money doesn't go "in their pockets" and they have no control over what their employers do with it.
-"In states that are working hard to make sure this law delivers for their people, what we're seeing is that consumers are getting a hint of how much money they're potentially going to save because of this law. In states like California, Oregon, Washington, new competition, new choices, market forces are pushing costs down."
THE FACTS: It is simply not known whether health insurance will become less expensive in those states - or nationally than it is now, or than it would have been absent the law. And hitches in setting up the new insurance marketplaces called exchanges are not limited to Republican-led states where leaders object to the law, although that political pushback is certainly part of what's going on.
In California, for example, where there is plenty of competition by health insurers wanting to get into the exchange, an actuarial report commissioned by Covered California, the state agency running the insurance marketplace, found that middle-income residents could see individual health premiums increase by an average of 30 percent while costs go down for lower income people.
In West Virginia, Democratic Gov. Earl Ray Tomblin - also a cooperative partner in expanding Medicaid and setting up an exchange - complained to federal officials this week about delays in rules and guidelines from Washington as the state struggles to meet deadlines under the law.
"Many West Virginia families have expressed frustration" trying to find out how much policies from the exchange will cost them and whether they will get a subsidy, he said, and the state is "dangerously close" to falling short of requirements under the law.
In case you had any doubt that Indian policy on pharmaceuticals isn’t predicated on domestic manufacturing policy …
A day after a high-level panel headed by Prime Minister Manmohan Singh relaxed foreign direct investment (FDI) norms in sectors ranging from telecom to single brand retail, he’ll be holding a separate meeting to review the policy in the pharmaceutical sector.
According to a senior official, "The main concern of the Ministry of Commerce and Industry is that a stage might come when India might not have a company ready to manufacture drugs on behalf of the government, even if the provision of compulsory license is invoked.”
Shouldn’t the fact that acquiring companies are paying huge valuations -- many time the cost of setting up new projects -- raise a question as to their motivation – and that of the Indian government?
Another example of domestic manufacturing policy trumping the public health?
It took only two months after patent expiry in China for two generic versions of Novartis AG’s blockbuster chronic myeloid leukemia drug Glivec (imatinib) (marketed as Gleevec in the U.S.) to gain China FDA approval, and many more are expected to follow suit. But Novartis plans to fight back by highlighting the quality and efficacy of its brand and its long-running patient assistance program.
Two companies received CFDA approval June 26, Jiangsu Hansoh Pharmaceutical Co. Ltd. and Jiangsu Chia-tai Tianqing Pharmaceutical Co. Ltd., or CTTQ, 60% of which is held by Hong Kong-listed Sino Biopharmaceutical Ltd. CTTQ holds the first capsule generic approval, while Hansoh received CFDA approval for a tablet formulation of imatinib. Generic imatinib for chronic myeloid leukemia will launch in August, Sino Biopharmaceutical said during a July 4 event.
Although the Glivec compound patent expired in China in April, Novartis still holds a beta crystalline patent in the country until 2018 and a patent for a gastrointestinal stromal tumors indication until 2021, Novartis China said. According to Novartis, the two China generics are likely alpha crystalline forms of imatinib.
“The generic has a different crystal type, so the product quality and treatment result will be totally different,” said Wendy Wang, head of communications for Novartis Oncology China.
The imatinib generics race is just warming up. According to CFDA’s database, as of July 16, there were 16 new applications for imatinib generics in 2013, including an imported drug application.
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.
