Latest Drugwonks' Blog

Truth in Biosimilar Labeling

  • 05.24.2016
  • Peter Pitts
From today’s edition of The Hill  …

Truth in biosimilar labeling
By Peter J. Pitts

Recently the FDA issued draft guidance on labeling for biosimilar products. In two words, no surprises – which for some is better news than for others.

The top of Page 8 will get a lot of attention:

FDA recommends that biosimilar product labeling incorporate relevant data and information from the reference product labeling, with appropriate product-specific modifications. The relevant data and information from the reference product labeling that should be incorporated into the biosimilar product labeling will depend on whether the applicant is seeking approval for all conditions of use (e.g., indication(s), dosing regimen(s)) or fewer than all conditions of use of the reference product for the biosimilar product.

And further:

In sections of the biosimilar product labeling that are based on the reference product labeling, it is anticipated that the text will be similar. Text based on the reference product labeling need not be identical and should reflect currently available information necessary for the safe and effective use of the biosimilar product. Certain differences between the biosimilar and reference product labeling may be appropriate. For example, biosimilar product labeling conforming to PLR and/or PLLR may differ from reference product labeling because the reference product labeling may not be required to conform to those requirements at the time of licensure of the biosimilar product. In addition, biosimilar product labeling may include information specific to the biosimilar product necessary to inform safe and effective use of the product, which could include differences such as administration, preparation, storage, or safety information that do not otherwise preclude a demonstration of biosimilarity.

To “inform safe and effective use.” Sounds good on paper – but what does it mean? Always? Sometimes? What are the parameters? If there’s information available, why not share it all the time? Or not at all? Who’s to judge? Can we rely on regulatory predictability – and this early in the biosimilar experience? Isn't more information better?

Of course, in order to maintain maximum regulatory, um, flexibility --

FDA acknowledges that there will be variations on the general concepts outlined in this section because the approach to product identification will depend on the specific statements.

(Note – author highlights, not FDA’s.)
An update article in Modern Healthcare makes an interesting point, “Federal regulators are likely trying to simplify physicians' understanding of the products' efficacy and safety. By definition, a biosimilar product has no clinically meaningful difference in terms of safety, purity and potency.”

If what practicing physicians understand about biosimilars is anything akin to the knowledge scale of the FDA’s Arthritis Advisory Committee -- as demonstrated during the meeting that considered the biologics license application for a proposed biosimilar to Remicade (infliximab) – then the agency’s attempt at “simplification” may result in some very serious unintended consequences. From the very beginning of the adcomm, it was clear the expert members of the committee didn’t understand what biosimilars really are, nor the pathway the agency uses to review them. Not good.

Per being upfront that the product is a biosimilar, the agency is unambiguous:

FDA recommends inclusion of a statement, on the line immediately beneath the initial U.S. approval date in Highlights, that the product is biosimilar to the reference product.

Although the FDA notes that the labeling does not need to be identical to information based on the reference product, it’s a pretty safe bet that manufacturers of biologics will likely take issue with competitors using their data for a product that is not exactly the same.
But from a straightforward public health standpoint, why omit truthful and accurate information from the information available to physicians and patients?

Shouldn’t labeling transparency be a key tenet in the Era of Biosimilars?

Building EvGen

  • 05.16.2016
  • Peter Pitts
What We Mean When We Talk About EvGen Part II: Building Out a National System for Evidence Generation

By: Rachel E. Sherman, M.D., M.P.H., and Robert M. Califf, M.D.

In an earlier FDA Voice blog post, we discussed a pair of concepts – interoperability and connectivity – that are essential prerequisites for the creation of a successful national system for evidence generation (or “EvGen”). In this post, we take a look at how we would apply these constructs as we go about building such a system.

Building EvGen

Creating knowledge requires the application of proven analytical methods and techniques to biomedical data in order to produce reliable conclusions. Until recently, such analysis was done by experts operating in centers that typically restricted access to data. This “walled garden” approach evolved for several reasons: the imperative to protect the privacy and confidentiality of sensitive medical data; concern about the negative consequences that could arise from inappropriate, biased, or incompetent analysis; and, the tendency to see data as a competitive asset. Regardless of the specific reason, the result has been the same: widespread and systemic barriers to data sharing.

If we are to reverse these tendencies and foster a new approach to creating evidence of the kind envisioned for EvGen, we must bear in mind several critical principles:

There must be a common approach to how data is presented, reported and analyzed and strict methods for ensuring patient privacy and data security.
Rules of engagement must be transparent and developed through a process that builds consensus across the relevant ecosystem and its stakeholders.
To ensure support across a diverse ecosystem that often includes competing priorities and incentives, the system’s output must be intended for the public good and be readily accessible to all stakeholders.What Would EvGen Look Like in Practice?

What would a robust national platform for evidence generation look like? It may be helpful to envision EvGen as an umbrella for all activities that help inform all stakeholders about making treatment decisions.

The task of evaluating drugs, biologics, or devices encompasses different data needs and methods. However, all share a common attribute: the characterization of individuals and populations and their associated clinical outcomes after they have undergone diagnostic or prognostic testing or been exposed to a therapeutic intervention.

Moreover, when medical practice itself is part of the evaluation, characterization of the organization and function of delivery systems is critical. In other words, the kinds of evidence needed to evaluate medical products for safety and effectiveness and the kinds of evidence needed to guide medical practice overlap substantially.

Over the last decade, there has been enormous progress in the area of “secondary use,” in which data collected for one purpose (for instance, as part of routine clinical care) can be reused for another (such as research, safety monitoring, or quality improvement).

The Sentinel Initiative, launched in response to a Congressional mandate to develop an active postmarket risk identification and analysis system, is one example. Modeled after successful programs such as the Centers for Disease Control and Prevention’s Vaccine Safety Datalink, Sentinel allows FDA to conduct safety surveillance by actively querying diverse data sources, primarily administrative and insurance claims databases but also data from electronic health record (EHR) systems, to evaluate possible medical product safety issues quickly and securely.

Another example, the National Patient-Centered Clinical Research Network (PCORnet), is a national system that includes many of the attributes needed for EvGen. PCORnet includes participation from government, industry, academia, and patients and their advocates. Whereas FDA’s Sentinel system is built primarily on claims data repurposed for safety surveillance, PCORnet is designed to leverage EHR data in support of pragmatic clinical research.

The NIH’s Health Care Systems Research Collaboratory has demonstrated through its Distributed Research Network that the concept of secondary data use can be extended into the realm of prospective pragmatic interventional trials. The NIH Collaboratory program, which includes many of the same health care systems involved in Sentinel and PCORnet, has 10 active trials underway.

In addition, the Reagan-Udall Foundation Innovation in Medical Evidence Development and Surveillance (IMEDS) Evaluation Program is exploring governance mechanisms to ensure that private-sector entities, notably regulated industry, can collaborate with Sentinel data partners to sponsor safety queries about marketed medical products. Such measures have the potential to expand the involvement of private-sector partners beyond the arena of methodology, further helping to ensure that Sentinel continues its expansion into a national resource.

Similarly, efforts are underway to establish a National Device Evaluation System (NDES). As currently envisioned, the NDES would be established through strategic alliances and shared governance. The system would build upon and leverage information from electronic real-world data sources, such as data gathered through routine clinical practice in device registries, claims data, and EHRs, with linkages activated among specific data sources as appropriate to address specific questions.

As substantial work already is being done in all of these areas, valuable experience is being gained. The next step is to ensure that these pioneering efforts coalesce into a true national resource. More on that in future postings.

Rachel E. Sherman, M.D., M.P.H., is FDA’s Associate Deputy Commissioner for Medical Products and Tobacco
Robert M. Califf, M.D., is Commissioner of the U.S. Food and Drug Administration
Yesterday Sara Edmond, the chief operating officer of the Institute for Clinical and Economic Review and I danced around whether ICER is really patient-centered as she claimed, or rebate-centered as I did. 

Ms. Edmond was a panelist at an  excellent Financial Times sponsored  US Healthcare Life Sciences Summit yesterday.  She was joined by Peter Bach, Director, Center for Health Policy and Outcomes, Memorial Sloan Kettering Cancer Center Jonathan Emms, Senior Vice President, Global Health and Value, Pfizer Jeff Myers, President and CEO, Medicaid Health Plans of America and Leonard Schleifer, President and CEO, Regeneron.

Praluent, the drug targeting people with untreatable high cholesterol was (along with Amgen’s Repatha) was considered low value by ICER and claimed that it should only be given to 15 percent of all patients who could benefit and at 80 percent of the list price.  

As a Reuters article reports, Dr. Schleifer blasted ICER as unscientific:

"They did all the calculations and they said it's X, which is ok. I could have lived with that. But ... they said society can't afford X, so we are going to say it's one-third X," Schleifer said during a panel discussion.
"They had value-based pricing, but they just decided that well we can't afford it. That wasn't scientific. There was no intellectual honesty there."

ICER Chief Operating Officer Sarah Emond, on a panel with Schleifer, countered that budget impact is part of the equation.
"You're attacking the science of an independent non-profit whose entire mission is tied to opening the black box of pricing," she said.

Which lead me to challenge Edmond from my seat in the audience about ICER’s so called independence. 

I said:  “ICER is not independent, it is largely funded and overseen by PBMs and insurers.”

Edmond responded that most the money came from the Arnold Foundation but I pointed out that the Arnold foundation grant is a one time thing.  

I then said that ICER’s value metric reflects the PBM and insurer interest and ignores patient value.  Further, the low QALY by default becomes a price control or price cap that doesn’t make drugs affordable or available.  Instead, the lower price only maximizes rebates that don't go to patients. More important, for all her talk about opening a black box I noted that ICER never mentions that PBMs run the $115 billion rebate racket.  

She said that since ICER doesn't have rebate data they have to use list price.

People laughed and Schleifer asked:  You estimate everything else, why not rebates? 

Finally I reiterated that under the ICER framework, not only would drugs for HIV, cancer, etc. be rejected but that next generation medicines would not be developed.    She responded, if we pay for Hep C drugs then we will have to lay off teachers and close schools." 

That drew another laugh.  

Edmond claims that ICER "uses science, we use math."  But she was unable to rebut the claim that the math supports the kind of creative accounting that reduces drug prices and maintain PBM and insurer profit margins. 

ICER's self anointed claim of being a trusted and independent organization was debunked.  Indeed, the other FT summit panelists talked about plans, providers and drug companies sustaining innovation and generating value while realizing that in doing so some ‘stakeholders’ – hospitals and PBMs – would go the way of Blockbuster video.   

Maximizing PBM and insurer rebate revenue is a self-serving enterprise that is sustained by increasing the spread between list prices and acquisition cost.   ICER was created and is funded by groups that profit from this enterprise to validate a QALY for that financial goal.  

In its current form ICER stands for the Institute for Constantly Extracting Rebates.

Now the black box is opened. 

The Urgency of the TPP

  • 05.12.2016
  • Peter Pitts
When it comes to global trade, there is no value to living in the past. We no longer trade in barter or beads. The Trans-Pacific Partnership (TPP) acknowledges that we live in a global village – and innovation is an essential commodity. Why are some people finding this so surprising? 

The evolution of the TPP has been long and arduous – but the basic premise has never changed. In order for global trade to flourish in an equitable manner, there have to be rules. Minus the rule of law, chaos ensues and we find ourselves in a survival of the fittest situation without fairness, predictability, or incentives for innovation. In a world without rules, ambiguity trumps investment and risk outweighs rewards.

One of the more important aspects of the TPP is intellectual property (IP) protection for biopharmaceutical innovation. This is of particular importance to the United States, where the U.S. biopharmaceutical research sector leads the world in the development of new medicines with about 4,000 in development or FDA review in the U.S. and more than 7,000 in development worldwide. This sector generates high-quality jobs and powers economic output and exports for the U.S. economy, serving as the foundation upon which one of the U.S.’ most dynamic innovation and business ecosystems is built. 

Read our new report here.

 If you give someone the tools they use to commit a crime, are you also responsible? 

Consider the following news item from Reuters about pharmacy benefit managers and their rebate contracts with drug companies: 

U.S. probes contracts between drugmakers, pharmacy benefit managers
“The U.S. Attorney's Office for the Southern District of New York is investigating contracts between drugmakers and companies that manage prescription benefits, according to regulatory filings… When drugs are knocked off their formularies, patients may have to pay full price for them. PBMs often keep or dump a product depending on whether they can obtain favorable pricing.”
As I have noted PBMs get and distribute about $110 BILLION in rebates each year.  That’s a trillion over a decade.  ICER plays, or seeks to play a role in setting prices and determining what products PBMs choose and insurers pay for that is central to enlarging and maximizing rebates.   And the PBMs are working closely with ICER to develop the price and access parameters of the contracts the  U.S. Attorney for the Southern District of New York is investigating:
“ICER’s new program will make a huge difference by providing what is sorely needed: an independent, trusted source of information about new drugs,” stated Steve Miller, MD, Chief Medical Officer of Express Scripts, the nation’s largest pharmacy benefits manager. “I believe many payers and policy makers will find this information of critical importance as they evaluate the new drugs, and we look forward to using it to help us improve the ability of patients to get access to new, innovative drugs at a price the system can afford.”
PBMs are also looking to ICER’s Steve Pearson to find reasons to pay less for cancer drugs depending on their indication. As a recent article noted: “ Express Scripts is using data from ICER, as well as the DrugAbacus, to inform its indication-based pilot.”
As I have noted before, indication pricing, based on average response and on a QALY measure reflecting PBM profit motives, can endanger patients and discourage companies from investing in treatments for the most difficult to treat tumors.  More generally, first in class or first ever drugs to treat the most severe conditions -- particularly rare diseases --  are likely to show modest benefit on average.  Such medicines will never meet ICER's devalued QALY measure. 
The most recent example is ICER has already determined that most new multiple myeloma drugs approved to treat patients whose disease has returned are NOT cost effective, even at 90 percent of the list price of the drug.
People with myeloma will bear moral, economic and clinical consequences that ICER ignores and the media barely mentions.   So two days before ICER meets to approve the report’s (foregone) conclusions I will be releasing a white paper that measures these essential values.
One important point to consider:  ICER recommendations would lead to drug companies forking over billions in rebates in exchange for putting these drugs on their formulary.   It does NOT mean that patients will get access.   It does mean that ICER is enabling the rebate ripoff scheme that the US attorney is investigating.  It may not be cutting the deals but ICER is supplying the PBMs the justification for the rebate enterprise.   


The American Journal of Managed Care ran a Q&A with Express Scripts and ICER consultant Peter Bach about his " DrugAbacus, the importance of using value frameworks, and using the European market as a model to recalibrate the healthcare system in the United States.

Bach likes to claim that he trying to reduce the mismatch between value and price.   That is a presumption without much basis in fact and is largely shaped by his Malthusian definition of value.   
Let's once again prove that Bach has an ideological axe to grind that has nothing to do with reality.  

In his interview, Bach claims that "it’s impossible to convince yourself that we are getting any incremental value, period, let alone any incremental value of the excess spending. If we compare ourselves with other countries, there does not seem to be any rationale, except that we simply spend more for all units of healthcare"  

I will get to his inaccurate assertion about other countries in a bit.  But first, let's look at his claim about incrementalism, one he has been repeating for several years.  Today and yesterday, Bach has ignored how cancer survivorship and life expectancy steadily increased over the past 20 years.   More recently, new drugs for lung cancer have doubled response rates and increased survival by 45 percent.  The total drug cost per patient (which includes the part of the price going to PBM rebates, etc.) is estimated to be between $36000-98000.   

He may believe that the  additional increment of average survival (which ignores genomic variation) is not worth spending money on.  But that ignores the fact that treatments are targeted to smaller populations that have fewer options than previous generations.  And he decidely believes that being able to live long enough to benefit from future medicines is a waste of time and money.

Bach knows better.  After all, one of his co-authors in the paper he cites in his NEJM oral hallucination about new drugs not adding more survival despite higher prices, makes that very point in another study: " In the absence of significant pricing and total oncology outlay flexibility by payers, our analysis suggests that private sector investment in small oncology segments, and in stratified medicine generally, may not prove economically sustainable, thus endangering the translation of scientific advances into bedside medicines. Beyond increasing reimbursement, decreasing development cycle time and costs, or both, would most directly improve the economic incentives facing developers. By contrast, extending exclusivity periods, or initiating advance market commitments and awarding prizes would likely have less impact and involve greater implementation challenges." (Trusheim, Berndt "Economics of Stratified Medicine" Personalized Medicine (2012) 9(4), 413–427)  
2.  Bach's main point: "The reality is that the drivers of healthcare spending in the US are unit price, not volume."
 To prove his claim Bach asserts: So, if we want to manage healthcare spending, you can make the argument that the excess price above that, which is being paid ambiently in European countries, is actually wasted dollars. It does not make the pill any better by paying 4 times as much for it."

That is untrue on two levels with respect to drugs. 
In developed markets, most growth is from new brands and increased volume, not price.  As the chart (from the IHI Oncology Trend Report: 2015

The IHI report notes: "Oncology drug spending has risen slightly as a percentage of total drug spending over the past five
years in all regions, most notably in the EU5 countries where oncology now represents 14.7% of total
drug spending, up from 13.3% in 2010, while the U.S. has seen oncology increase more modestly from
10.7% to 11.3% of total drug spending over the same period."

Indeed, the US rate of spending was lower compared to Europe even though  US adopts new medicines more quickly than Europe and other developed countries.  
 Yet the share of oncology of total drug spend is lower and increased more slowly in the US.
The IHI report estimates total spending on cancer drugs in the US is $42 billion.   Forty eight percent of that spend is for targeted therapies ($20 billion)   Total drug spending was $425 billion (without rebates) so new therapies are about 4.7 percent or that amount, which is unchanged since 2010.    Cancer drugs as a percent of total health care spending remains at about 1 percent.    

But Bach claims cancer drugs cost four times as much here than in Europe.  
As an aside, Bach’s claim that drugs are 6 times more expensive in the US than in Europe is an absurdity.   I can find a drug on the UK NHS formulary that has been subject to price concessions and price controls for a decade and compare it retail price here.  But that ignores the fact that in most cases the US is using generic drugs that are less expensive than the brand drug Bach has selected.   And with respect to cancer drugs the acquisition price of new products are about the same.   For instance, the retail price of a 50ml vial of Keytruda in the US is about $2200.   In the UK it is $1900.   A year supply of 40 mg crestor is (US dollars) is $4300 and the retail price in the US is  $2280.   A year’s supply of Januvia in the UK is 3326 pounds or $4800 while the retail price in the US is $4552. 
Finally, he glosses over the inequities of applying a QALY to a class of drugs or indication without regard to genomic variation or the severity  of the tumor being treated.  That's because he has a vested interest in using QALY to devalue new medicines which in turn allows the PBMs and insurance companies he consults for to rake in billions more in rebates.  And this devaluation will also hurt and even cause cancer patients to die. 
As I noted in a previous blog reviewing another work of fiction by Bach, "In an article published last year in the Journal of the American Medical Association, he suggested that in an indication-specific arrangement, the monthly price for Eli Lilly & Co.’s cancer drug Erbitux (cetuximab) would plummet from $10,320 a patient to about $470 a patient for its least effective use, treating recurrent or metastatic head and neck cancer. The drug also is used to treat locally advanced head and neck cancer, as well as colorectal cancer."
 Bach claims that the use of Erbitux for head and neck cancer is a "least effective use".  Let's set side the curious math used to arrive at the $470 figure.  It is more important to note that Bach ignores not only individual differences in response but the impact of Erbitux relative to existing need and treatment protocols.     Bach uses an average 2.3  months more of survival as his benchmark.   
Here's what we know about pre-Erbitux treatment of recurrent, metastatic squamous cell carcinoma of the head and neck (SCCHN):
"None of the trials performed in the past, even those with a reasonable sample size, have shown that aggressive platinum-based combination chemotherapy leads to survival benefit when compared to single agent methotrexate, cisplatin or 5-fluorouracil.
What difference does Erbitux makes?  
After decades without real progress, a recent European randomized trial showed that adding cetuximab, the first clinically available EGFR-directed monoclonal antibody, to a standard chemotherapy regimen (platinum/5-fluorouracil) leads to an important survival benefit and this, with support of an additional smaller study in the US, has changed practice."  J. B. Vermorken and P. Specenier Optimal treatment for recurrent/metastatic head and neck cancer. Ann Oncol (2010) 21 (suppl 7): vii252-vii261 doi:10.1093/annonc/mdq453
Hence, the Bach pricing approach would whittle away payment for the hardest to treat cancers for patients that have had no real advances in care for decades.  Maybe Bach supports paying doctors less for people who are the farthest gone because the relative health gains are well, not worth it??

Bach never comes clean about who benefits from the discounts he proposes.  In the US, it's the PBMs and insurers.  Currently, these special interests rake in about $4-8 billion in rebates on targeted oncology drugs.   Meanwhile patients are forced to use drugs that generate the most rebates and have to pay a large portion of the retail drug cost on top of everything.  

I guess that's linking prices to one set of interests -- PBMs and insurers -- that Bach values more than what is best for patients.  

Purple Reign

  • 05.11.2016
  • Peter Pitts
Much ado about an article in Morning Consult by Ronald T. Piervincenzi (Chief Executive Officer of the United States Pharmacopeia) and Thomas E. Menighan,  Executive Vice President & Chief Executive Officer of the American Pharmacists Association).

According to their commentary, Legislation Threatens Patient Confidence in Biologics, Slows Biosimilars, legislative language in the Senate’s FDA and NIH Workforce Authorities Modernization Act would impede “the one issue uniting policymakers” -- the need to improve our system for getting low-cost quality-assured therapies to patients quickly.” How? “… by exempting biologic medicines – including biosimilars, insulin, blood thinners, cancer treatments and other drugs – from having to comply with public standards for quality.”

That’s a pretty strong statement and a lot of people should (rightly) take offense. But it raises an important issue – why the vitriol? 

It’s a complicated issue with many moving parts, all of them worth serious debate. For those in on the issue, the under-current renews the continuing tension between USP and FDA on many matters relative to biosimilars.

It’s important that these two institutions work together in many places and understand each other’s individual efforts -- not the least of which is the continuing evolution of the FDA’s new Purple Book.

The “Purple Book” lists biological products, including any biosimilar and interchangeable biological products licensed by FDA under the Public Health Service Act (the PHS Act). The lists include the date a biological product was licensed under 351(a) of the PHS Act and whether FDA evaluated the biological product for reference product exclusivity under section 351(k)(7) of the PHS Act.

The Purple Book will also enable a user to see whether a biological product licensed under section 351(k) of the PHS Act has been determined by FDA to be biosimilar to or interchangeable with a reference biological product (an already-licensed FDA biological product). Biosimilar and interchangeable biological products licensed under section 351(k) of the PHS Act will be listed under the reference product to which biosimilarity or interchangeability was demonstrated.

USP and FDA both have important roles to play. It’s a very small sandbox with very large public health implications.
Following the advice of Peter Bach, who holds the Express Scripts Chair for Rebate-Driven Outcomes Policy at Memorial Sloan Kettering, the Center for Medicare and Medicaid Services (CMS) has proposed paying cancer doctors less for administering the most expensive cancer drugs covered  under Medicare part B.  A lot of people -- including the oncologists themselves --have been complaining about the cut.  But nobody has talked about the most unethical part of the experiment:  As Drug Channel's Adam Fein explains:

"CMS wants to reduce reimbursement for buy-and-bill drugs—but for only half of the country's providers. The other half will retain current reimbursement levels. After five years, CMS will see what happened. .."

As only Adam has pointed out this is an unprecedented experiment on patients.   

Did anyone ask Medicare consumers if they wanted to participate?  Did CMS offer to pay moving costs to people who want to be in the control arm of this experiment?   

Did anyone ask if this was even ethical?  Here's what the NIH Office of Human Research Protection guidance on informed consent requires.  You tell me if the Medicare Part B experiment comes within a light year of this moral galaxy:

" Disclosing the reasonably foreseeable risks of research to prospective subjects recognizes the ethical obligation to give prospective subjects sufficient information to make a knowledgeable decision about whether or not to participate. This reflects the ethical principle of respect for persons, which recognizes the importance of giving individuals sufficient information during the informed consent process to make a considered judgment about whether to participate in research that could affect their health or wellbeing—for better or worse."

The CMS notice does not address any of these issues.  Indeed, the phrase informed consent doesn't even show up in the proposal.


"Providers, suppliers, and beneficiaries who are included in the model will have access to the existing claims appeals process, as well as a proposed Pre-Appeals Payment Exceptions Review process, to resolve disputes arising from the policies implemented by this model. "

In otherwords, no informed consent, not even passive consent.  Instead, patients are being hereded into an experiment that in my opinion, violates EVERY canon of the Nuremberg Code 

To be fair, my guess is the position of CMS is that of many people like Peter Bach who believe that price-driven treatment selection does not required informed consent as long as you create a website for your cancer abacus.  But even those who want limits on informed consent in comparative effectiveness trials would do so if patients were not assigned to the treatment arm.  

CMS informs no patient.  The guidance does not require doctors or  hospitals to do so. 

This is a deliberate attempt to side-step informed consent.  And the Part B human experiment is just one part of a larger effort to limit patient choices in what are actually natural experiments by dressing them up as comparative effectiveness research. 

I suggest anyone involved in the Part B human experiment read George and Catherine Annas' article on Therapeutic Ilusion to understand just how unethical the project is.  The authors note: 

"Historically, misleading and confusing terms such as “therapeutic research,” “experimental treatment,” and “invalidated
treatment” have been used to blur the distinction between research and treatment. Similar misleading terms are being deployed in an effort to make evidence-based medicine research (including comparative-effectiveness research) easier to do by dispensing with or watering down disclosure requirements."

By convincing themselves that the law of informed consent does not apply to treatment...The radically paternalistic result would be that physicians could not only set the “standard of care” for medical interventions—whether research or treatment—but also set the “standard of care” for informed consent for both. That quest is, we think, dangerous to the autonomy and dignity of patients and should be repulsed not only by patients, research subjects, and the public, but by physicians and researchers as well."


Califf's Inclusive "We"

  • 05.06.2016
  • Peter Pitts
At yesterday’s annual FDLI conference, FDA Commissioner Califf said that, “to achieve innovation, we must take risks.” And he wasn’t using the royal “we.”

He reiterated that one of his top priorities is to focus on staffing. (He also mentioned that he has about 100 “top priorities.”) There’s an important connection. The FDA’s ability to be an innovation enabler is directly linked to the issue of staff. Not necessarily more staff (although more is certainly better), but staff that is permitted, encouraged, cajoled, urged, directed, educated, and rewarded for taking risks – especially outside oncology and orphan diseases.

It’s slow going. There was solid momentum in the creative thinking of divisional staff in the early days of the new millennium, the McClellan years. But this nascent trickle of “entrepreneurial regulation” hit treacle in the face of the Vioxx imbroglio. It was a battle worth fighting – and winning. The agency is still recovering.

The good news is the agency has come a long way back. New pathways for approval are on the books with some notable clinical successes. New thinking on clinical endpoints and biomarkers, the patient-focused drug development initiative (with the patient voice evolving from tellers-of-sad-stories to allies in clinical development), and more robust programs on quality and pharmacovigilance have infused some inside the FDA to think outside the regulatory box. But entrepreneurial regulation must be more than the “some” of its parts. Proposed legislation could help advance and encourage these and other initiatives but, as the Commissioner commented at the FDLI event, new laws mustn’t allow drugs to enter the market that don’t provide therapeutic benefit. Amen and words to the wise.

Embracing the risks of expedited pathways and other aspects of 21st century entrepreneurial regulation requires better internal agency communication, collaboration, and coordination. If victory in that realm becomes the Califf legacy, it would be a hugely important one for both the FDA and the public health. Success rests, as FDA Chief Counsel Liz Dickinson so eloquently phrased it, “on the infusion of new people and novel ideas.”

The policy of being too cautious is the greatest risk of all. -- Jawaharlal Nehru
How the mighty have fallen.

Once a newspaper of national importance, the Los Angeles Times has become a shadow of its former self. Consider it’s latest Page One investigation into Purdue Pharma. The drug manufacturer's malfeasance? Promoting on-label claims.


Here’s a link to the article and here’s a link to Purdue’s response.

According to Purdue, “In an attempt to resurrect a long-discredited theory, the paper ignores the clinical and regulatory data that directly contradicts their story.”

And they have the facts and citations to prove it. All of it.

Further, “Over the course of two years, Purdue Pharma provided the LAT with more than a dozen hours of briefings and discussions regarding the clinical evidence supporting OxyContin’s 12-hour dosing and the regulatory requirement that we promote the product as such. Unfortunately, the paper disregarded this information, instead publishing a story that’s long on anecdote and short on facts.”

Two years and the Times got the story so wrong? That’s bad news for the paper’s readers who expect and deserve better. Maybe it’s good news for the salivating tort bar. But before they start filing lawsuits, they better get the rest of the story.

For example (per Purdue):

CLAIM: OxyContin has a 12-hour dosing “problem” that puts patients at risk.

FACT: Nearly a decade ago, the FDA cited a lack of clinical evidence when it formally rejected the “fundamental premise” that patients receiving OxyContin at intervals more frequent than twice-daily are at increased risk of “side effects and serious adverse reactions.” In doing so, the agency reinforced the twice-daily labeling for OxyContin. The LAT omitted the findings of this report from its story.


And my favorite:

CLAIM: Purdue should tell physicians to prescribe OxyContin for eight-hour use.

FACT: The FDA prohibits pharmaceutical companies from promoting their products for uses, including dosing, not approved by the agency. Given FDA has not approved OxyContin for eight-hour use, we do not recommend that dosing to prescribers. In fact, a State Attorney General recently cited a peer company for falsely claiming that OxyContin was an eight-hour drug. The LAT omitted this piece of information from its story, falsely claiming that OxyContin was an eight-hour drug. The LAT omitted this piece of information from its story.

Is there a fact checker in the house?  Ouch.

There are so many serious issues surrounding opioids that the lack of professionalism by the LA Times is astounding.

I guess the Times ace I-Team can forget about that Pulitzer.

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.

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