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Some thoughts on Expanded Access and so-called "Right to Try" legislation from Pat Furlong, the Founding President and CEO of Parent Project Muscular Dystrophy (PPMD) and Tim Franson, Chief Medical Officer at YourEncore.:

Peter: How do you feel about Right to Try legislation and expanded access? Should language and deliverables for expanded access issues be in PDUFA VI?

Pat Furlong: Right to Try legislation is an outcry by the patient community to get some access some way, some how. The Right to Try bills I’ve read, are variable but in general have no real meat on them that give you the pathway to get what you’re looking for. There’s a lot left on the table that is not understood by the patient community.

That said, trials are so narrow.  In the Duchenne space there was a study that used the six-minute walk test and invited anyone who was ambulatory and had the diagnosis.  What we learned from that study is that the sort of sweet spot or area in which we can look at a sensitive measure are children who walk between 250 and 400 meters.  Now, you can imagine if you were a parent in a disease where the child is diagnosed between four and six years old.  He reaches a plateau at about seven or eight in terms of ambulation and then starts to lose those functions. By the time he’s 11 he’s off his feet. By the time he’s 13 or 14 he doesn’t move his arms.  And dead by about 25. So if you’re a little boy, if you’re four years old, you can’t be in the study because it’s seven years and above. If you’re non-ambulatory or if you walk slower than 250 meters or faster than 400, you’re off the bus. And you can imagine being screened for a clinical trial and the physician says to you, “Your son walks too fast. Come back when he’s slower.” Knowing the trajectory of this illness and you say, “What?  I’ll come back in six months when he’s slower?”  Expanded access has to be on the table for these patients because they only have one opportunity.

Peter: Why do pharmas put these rules in place?

Pat Furlong: Companies are reluctant (to offer expanded access programs) because of the expense and because of the worry that it could negatively impact their study. What the Right to Try legislation represents is the importance of providing opportunities and access to patients in need. I think foundations could come in and work with companies if we can understand how they price drugs and be able to support safety studies to include a wider range of patients.

Tim Franson: FDA is not the problem with expanded access. We do have an opportunity perhaps to create new ways to approach the issues associated with expanded access. For rare diseases, what if you could promote all the companies contributing to a common placebo database so that you don’t have to replicate that with every trial? Then that’s good for the patients, that’s good for the development process, and it changes how we approach expanded access issues.

My Take:

Perhaps, as part of the FDA’s current initiatives to enhance both the timeliness and weight of the patient voice, expanded access plan development and execution should involve patient organizations. Maybe it’s time to harness that power to make the process both more-inclusive and better.

Another issue that remains at-large is who pays for access to these unapproved drugs? What a company can charge is regulated (via draft guidance), but sometimes the drug company will bare all costs, other times some costs, and just as often it’s the patient who writes the check. And IRB and other related costs are often borne by the patient. Perhaps there’s a role for the Federal government. How about a fund that pays for access for any approved FDA expanded access IND or protocol?

All sides want the same thing -- expedited expanded access programs. But name-calling and bridge burning doesn't bring anyone closer together or experimental drugs to dying patients any faster. Let’s expedite access by enlarging the Expanded Access Ecosystem.

Ahead of a Trans-Pacific Partnership (TPP) ministerial meeting later this week, a naïve attempt by the Senator from Ben & Jerry’s to generate some post-Papal ink …

WASHINGTON, Sept. 28 – Sen. Bernie Sanders (I-Vt.) today asked the chief trade representative for the United States to ensure people in the poorest countries around the world have access to low-cost medicines.

“Making sure people in poor countries have access to life-saving medicine is our moral responsibility,” Sen. Sanders wrote. “The European Commission and the Holy See both support a permanent exception for drug patents for these poor countries. The United States government should support this as well. Lives are at stake.”

Bernie, FYI -- When you examine the WHO’s model Essential Drug List, very few of the 400 or so drugs deemed essential are new, or patented or were ever patented in the world’s poorest countries.  In category after category, from aspirin to Zithromax, in almost every case and in almost every country, these medicines have always been (or have been for many years) in the public domain.  That is, the medicine is fully open to legal and legitimate generic manufacture.

As John Adams said, “Facts are pesky things.”

Two weeks ago, I covered “The Top 10 Regulatory Issues for Today’s Drug Developers.” One of the 10 regulatory policy topics that keeps me up at night is patient focused drug development – specifically, how can patients help drive development? This topic is even more relevant and complex in the rare disease space.

PDUFA V introduced incentives for rare disease development but other key questions were unaddressed: how to include the patient voice and what is the proper role of advocacy groups, agencies, and industry? In the recent past, the patient voice was limited to teary anecdotes. Parent Project Muscular Dystrophy (PPMD), however, has made groundbreaking strides introducing the patient voice into the Duchenne muscular dystrophy development process – and giving other disease communities a blue print to follow.

I had the opportunity to moderate a panel discussion with Pat Furlong, the Founding President and CEO of PPMD, about this topic and I’d like to share some of this exchange.

Peter: What are your feelings on how PDUFA V moved incentives forward?

Pat: I think PDUFA V crystalized the need for and importance of patient focused drug development, but it gave no definitions or metrics on how it should be done. How do we include a patient voice? What does it mean? How do we incorporate it in a sufficiently rigorous way? This led to PPMD’s interest in benefit/risk and the need to quantify benefit/risk (caregiver/patient preferences) for our patient community. We did a pilot in an effort to explore this with our community and I am hopeful that it set the stage for the broader rare disease community to begin exploring the equation within their communities.

I feel like PDUFA V was an open door to develop models for engagement. Clearly this is new and the FDA is exploring opportunities to include patients/caregivers to better understand their preferences and what matters to patients. The FDA is driven by data and in that, patients have an extraordinary opportunity to engage, to inform, and to develop models and systems in which the patient preferences are known and understood and considered within the review process.

Peter: Is there a shift among the patient community from being social support groups to becoming a source for clinical trial recruitment, outcomes research and benefit/risk social science?

Pat: I think it depends on where you are in the rare disease community. Social networking encourages people to start their own foundation to do something, but for regulatory agencies, it may not be enough to tell your story. We have to be good partners and scientific partners. We who have been here a bit are looking at how to provide data in terms of benefit/risk, how to look at these patient reported outcomes in a rigorous way, and the value of engaging with the Critical Path Institute to develop a disease progression model. We believe good partnerships are critically important for Duchenne and the rare disease community, and we are able to provide the scientific data that’s going to be important and useful for the approval process.

Peter: What’s your biggest ask for PDUFA VI?

Pat: The big ask for PDUFA VI would be more transparency in the review process. Obviously the FDA is not allowed to give a confidential report of what was discussed, but I would like to see them inform the disease community about what was included in that review. Was benefit/risk data available? How did the benefit/risk inform their thinking? Were PRO (patient reported outcomes) available and if so, considered in the review process? For the patient community, it is important to understand what was included in the review process and how that informed/contributed to the regulatory decision.

PDUFA VI discussions are underway and here’s my take on how patient-focused drug development (PFDD) may evolve under the new act:

  1. What happens after the agency has held a disease-specific conversation? Will the agency devise a way to train patient organizations to create draft guidances for treatment pathways?
  2. How early in the development process should the patient voice be heard? Can PFDD mean more than just a variable in the benefit/risk conversation?
  3. What about adaptive licensing? Will the patient voice be a potent one when it comes to Phase IV requirements

Next week, I’ll highlight other experts from this panel discussion and talk about expanded access and Right to Try Legislation.

A savvy move from FDA – choosing someone who understands quality from the other side of the proposition. Only the most recent way that FDA is working to redefine 3D quality and pharmacovigilance.

For more on OPQ and the FDA's Quality Revolution, see here.

Here’s the official announcement from Janet Woodcock:

CDER Staff:

I am pleased to announce that Michael (Mike) Kopcha (“cop-cha”), Ph.D., R.Ph., a globally-recognized expert in product innovation and development, has been selected as the permanent director of the Office of Pharmaceutical Quality (OPQ). He will join CDER in November pending ethics clearance.

Mike is a leader in the development of innovative solutions to resolve scientific, manufacturing, and commercialization issues worldwide – and in standardizing and harmonizing global processes. With more than 25 years of pharmaceutical industry experience, his areas of expertise include formulation and process development, process validation, technology transfer, off-shoring/outsourcing, and change management.

OPQ – with close to 1,000 employees – was stood up in January to carry out new processes and policies to provide better alignment among review, inspection, and research functions. As OPQ director, Mike will take over the reins from me in matters relating to pharmaceutical quality regulation. These include submission review, manufacturing facility assessment, and quality surveillance.

Mike recently served as vice president, and global research and development franchise head, for cough, cold, and respiratory products at Novartis Consumer Health, Inc. in New Jersey. He joined Novartis in 2008 as the global head for pharmaceutical and analytical development, later serving as global head for new technologies and product innovation, and vice president and global head for global product development.

At Novartis, Mike has led the creation of a global R&D vision and strategies to drive innovation for the cough, cold, and respiratory franchise – through development, sourcing, manufacturing, and supply. He restructured and reorganized global product development to provide for a category-focused, globalized organization, and is credited for the creation of a successful strategic off-shoring/outsourcing program to increase project capacity and efficiency.

Before joining Novartis, Mike served as vice president for pharmaceutical development at KV Pharmaceutical, Inc. in St. Louis, where he directed and managed analytical research and development, product development, process development and technology transfer, stability, drug delivery, project management, and external alliance. His experience also includes related roles with Schering-Plough, J&J, and Ivax.

Mike earned his doctorate and master’s degrees in pharmaceutical science, and a bachelor’s degree in pharmacy, from Rutgers University in New Brunswick, New Jersey. He served as an adjunct assistant professor in the Department of Pharmaceutics, Ernest Mario School of Pharmacy at Rutgers.   

Mike will lead OPQ in planning and implementing strategies to drive pharmaceutical quality, with a goal of providing for an efficient pharmaceutical manufacturing sector that reliably produces high-quality medicines without extensive regulatory oversight.

I’d like to thank OPQ Deputy Director Lawrence Yu for his tremendous leadership, guidance, and support as we worked to stand up OPQ, and for assuming many additional responsibilities during my period as acting OPQ director.

Please join me in extending a warm welcome to Mike when he joins us later this fall. He will be a true asset to CDER and OPQ leadership. His broad knowledge and expertise in product development and technologies will allow him to play an essential role in our continued work to assure that the public has access to safe, effective, and high-quality medicines.

Janet Woodcock

From today's edition of the New York Post ...

Why People Don't Trust Drug Makers

By: Peter J. Pitts

When former hedge-fund manager and current Turing Pharmaceuticals chief executive Martin Shkreli hiked the price of his generic anti-parasitic drug pyrimethamine from $13.50 to $750 per pill, he invited understandable national outrage. He also prompted presidential candidate Hillary Clinton to call for price controls on a wide variety of medicines.

The subtext here is clear: Americans think price-gouging on prescription medicines is rampant. This isn’t surprising, since the pharmaceutical industry has done a poor job of explaining why drugs cost what they do. More than three-quarters of Americans support mandatory limits on the price of certain drugs. And 86 percent want drug firms to disclose how, exactly, they set prices.

The best way for drug firms to quell this outrage is to give Americans what they’re asking for: more information. Specifically, the industry needs to shed light on the huge sums they spend on research, their rising research-and-development failure rates and the refusal of insurers and pharmacy-benefit managers to pass on manufacturer discounts to patients.

Of course, drug pricing is a complicated matter. Which is why the industry should focus on a few basic points when making its case.

First, the cost of research. Since 2000, drugs firms have spent over half a trillion dollars developing new medicines. And research costs for the last year alone totaled more than $51 billion. That’s up from $15.2 billion in 1995.

These are extraordinary spending levels, even compared to other research-intensive industries. In fact, the pharmaceutical sector spends five times more on R&D than aerospace, and 2 ½ times more than the software and computer industry. This is the kind of investment that pharmaceutical innovation demands, and it’s reflected in the economics of advanced drugs.

The industry also needs to do a better job explaining just how many failures firms endure searching for the next breakthrough medicine. Drug companies must develop hundreds of compounds until they find one suitable for testing on humans. Of those rare compounds that make it to phase-1 human trials, fewer than 12 percent win approval from the FDA.

That’s why bringing just one drug to market costs an average of nearly $2.6 billion and takes more than 10 years, according to researchers at Tufts.

If drug companies were open and honest about their frequent and expensive failures, they could quash the myth that pharmaceutical research is obscenely lucrative.

Drug prices aren’t merely the result of high development costs. The price of any given drug is the result of a lengthy process of meetings and negotiations between manufacturers and payers over a long period of time — often years before the FDA approves a product.

So when insurance companies demonize the pharmaceutical industry for high drug prices, they’re being more than a little disingenuous. Insurers and pharmacy benefit managers — not drug companies — are the ones who determine what patients pay for medications.

Consider the controversy surrounding the hepatitis C drug Sovaldi. When the medicine came on the market, it quickly became known in the press as “the $1,000 pill.” This may be a great sound bite, but it’s hardly accurate.

In reality, insurers and benefit managers negotiated discounts that reduced the price of Sovaldi by 20 to 50 percent. But they didn’t pass the full discount on to the consumer. Instead, insurers and pharmacy benefit managers pocketed the money to pad their bottom lines and executives’ wallets. Last year, CVS Caremark Corporation, one of the biggest benefit managers, paid its CEO over $32 million.

For many patients, particularly those without insurance coverage, Sovaldi’s manufacturer supplied a coupon ensuring that co-pays for the drug wouldn’t exceed $5.

In other words, the manufacturer went out of its way to ensure that few would have to pay full price for Sovaldi. In cases where patients had to shell out for “the $1,000 pill,” insurers were mostly to blame.

Most Americans, of course, are largely unaware of this information, which is why opinions have turned so sharply against the pharmaceutical industry. If they intend to win back the public, drug companies have some explaining to do.

The CDC’s been exceedingly secretive during the drafting of its controversial opioid prescribing guidelines for physicians, refusing to disclose its outside advisors. The panel of advisors is known within the CDC as the Core Expert Group. (The proposed guidelines, which were released this week, have angered many pain patients who think they could lead to sharp reductions in the prescribing of opioids for both acute and chronic pain.)

The only thing the CDC would say is that, “The Core Expert Group includes a limited number of CDC scientific staff, primary care professional society representatives, state agency representatives, experts in guideline development methodology, and other subject experts.” What’s missing? How about pain experts?

But when a federal agency tries to hide what should be an open and transparent process, sunshine has a way of breaking though the curtains. Here for the first time (and from inside the belly of the beast) is the CDC’s confidential document, CDC Guideline for Prescribing Opioids for Chronic Pain.It includes a complete list of the Core Expert Group. That group for the first time is now public knowledge:

Core Expert Group

  • Pam Archer, MPH; Oklahoma State Department of Health
  • Jane Ballantyne, MD; University of Washington (retired)
  • Amy Bohnert, MHS, PhD; University of Michigan
  • Bonnie Burman, ScD; Ohio Department on Aging
  • Roger Chou, MD; Oregon Health and Sciences University
  • Phillip Coffin, MD, MIA; San Francisco Department of Public Health
  • Gary Franklin, MD, MPH; Washington State Department of Labor and Industries/University of Washington
  • Erin Krebs, MD, MPH; Minneapolis VA Health Care System/University of Minnesota
  • Mitchel Mutter, MD; Tennessee Department of Health
  • Lewis Nelson, MD, New York University School of Medicine
  • Trupti Patel, MD; Arizona Department of Health Services
  • Christina A. Porucznik, PhD, MSPH; University of Utah
  • Robert “Chuck” Rich, MD, FAAFP; American Academy of Family Physicians
  • Joanna Starrels, MD, MS; Albert Einstein College of Medicine of Yeshiva University
  • Michael Steinman, MD; Society of General Internal Medicine
  • Thomas Tape, MD; American College of Physicians
  • Judith Turner, PhD; University of Washington

According to the document, the CDC, “aimed to minimize conflict of interest, enhance objective assessment of the evidence, and reduce bias.” Well, they may have aimed – but they missed badly. The members of this group do not represent a broad spectrum of thought on opioids. To put it nicely, the issue of normative bias needs to discussed –loudly and openly.

Consider Jane Ballantyne.

Ballantyne last year was named President of Physicians for Responsible Opioid Prescribing (PROP), a controversial organization that has lobbied Congress and criticized the Food and Drug Administration for not doing more to limit opioid prescribing. And in her conflict disclosure (see page 39 of the CDC document), she discloses her services as a paid consultant to Cohen Milstein Sellers & Toll – the same law firm referenced by the New York Times as shopping around opioid litigation – and having guidelines from the CDC that recommend restrictions in opioid prescribing could certainly be advantageous to such an endeavor.

As Pain News Network has reported, “The CDC and PROP appear to have a close working relationship — a link to PROP literature recommending “cautious, evidence-based opioid prescribing” can be found — unedited — on the CDC’s website.

According to Bob Twillman, Executive Director of the American Academy of Pain Management (one of the stakeholder groups that will be consulted by the CDC):

Clearly, this is PROP’s way of getting what FDA didn’t give them when they advocated for an ER/LA opioid label change. I don’t think it’s a coincidence that this sets a 90 mg MED dose limit, when PROP advocated for a 100 mg MED dose limit in their Citizen Petition to the FDA. That PROP’s president and one vice-president are part of the core expert group; their executive director and a board member are part of the stakeholder review group; and another board member is one of the three who will help edit the guidelines after the stakeholders report, all is not a coincidence, and clearly puts their fingerprints all over this guideline. But, of course, no one is supposed to know that.

And where is the FDA? According to the CDC, “FDA has been involved in the review process of the guidelines and we will continue to work with them on this prescription drug overdose epidemic.” If that’s true, why wasn’t an FDA expert included in the Core Group?

Per Twillman, In assessing the validity of the guidelines there are two factors that make up that validity assessment: the quality of the underlying evidence and the qualifications of the person making the recommendation. In the best case, of course, you want someone who is highly qualified making recommendations on the basis of high-quality evidence. That isn’t the case here, because CDC itself, in the review document, rates 8 of its 13 recommendations as having “very low quality of evidence” and 5 as having “low quality of evidence”. They also note that 12 of their 13 recommendations are “strong recommendations”, and only one (on UDT) is “weak.” In the absence of even moderate quality evidence, though, any recommendation really constitutes an opinion, creating an “eminence-based guideline,” not one that is “evidence-based.” In that case, the qualifications of the person issuing the unsupported opinion are VITAL to assessing the validity of the recommendation. If we are talking about a guideline that SHOULD be about how to use opioids to treat chronic pain, then shouldn’t we have more than one person in the core expert group who has extensive experience doing just that?

And that’s a question worth asking in open public debate.

It's easy to claim Turing Pharmaceuticals 5000 percent price hike of Daraprim is another example of how biopharmaceutical firms do business.

Easy, but untrue.

Here's Adam Feurstein of the explaining why he nominated Martin Shkreli as one of the worst biotech CEO's of 2014

Someone thought a smart but attention-addled man-child with a Don Bailey obsession and a Twitter account  could be a biotech CEO. They were wrong

In a previous post, Adam explains:

In the weeks before his ouster as the CEO of Retrophin (RTRX - Get Report) , Martin Shkreli was buying relatively small amounts of the company's shares on the open market and using his personal Twitter account to convince investors to do the same.

But while talking up Retrophin's prospects publicly and buying some of the stock, Shrekli was selling privately a much larger portion of his drug company holdings. Without public disclosure, Shkreli received almost $3 million in gross proceeds by selling "forward contracts" on his Retrophin stock in early September, according to a filing with the Securities & Exchange Commission made public Monday night.

Shkreli has not been accused of breaking any securities laws during his time at Retrophin. Last August, Retrophin's board admonished Shkreli for a series of inappropriate Twitter posts and the discovery that company employees were using alias Twitter accounts to promote Retrophin stock and make short-sale recommendations on other biotech stocks.

The new disclosure detailing Shkreli's selling of Retrophin shares comes at a delicate time. The former hedge fund manager has tried to restore his credibility and tamp down talk about his behavior and executive decision-making by blaming Retrophin's problems -- and his exit -- on the company's board and reporting by the media. At the same time, Shkreli is trying to raise outside investor money to finance a new company, Turing Pharmaceuticals.

Here's how Shkreli received almost $3 million in proceeds by selling Retrophin shares with delayed public disclosure:

On Sept. 9, Shkreli and an unnamed third party entered into a "prepaid forward contract" under which Shkreli promised to hand over 123,000 shares of Retrophin in two years. In exchange, the third-party buyer paid $1.07 million in cash to Shkreli -- an amount equivalent to 68% of the present value of the pledged Retrophin shares."

Again, courtesy of Feurstein on June 13 2011:

"As Neoprobe prepares to seek U.S. approval for its lymph node mapping agent, a New York hedge fund manager has shorted the stock and is taking an unusual step to prevent the company from getting a review by regulators.Martin Shkreli ofMSMB Capital Managementfiled a citizen petition with the U.S. Food and Drug Administration last week requesting Neoprobe's Lymphoseek be denied a review due to "severe deficiencies and flaws" in the conduct of two phase III clinical trials. Betting against FDA drug approvals is a well-worn (and often profitable) strategy in Wall Street's biotech trading canon. Shkreli, however, is pushing new boundaries by seeking to directly influence the FDA review process in his favor."

In 2013, Shkreli asked to speak before an FDA panel to argue against the approval of Lorcaserin, a weight loss drug made by Arena Pharmaceuticals Inc.  He had short positions in both Neoprobe and Arena

And here's an item that occured around the time Shkreli was raising $90 million for Turing.  

Retrophin Inc. founder Martin Shkreli, replaced last year as chief executive officer of the biopharmaceutical company, is under investigation by U.S. prosecutors in Brooklyn, New York, for possible securities law violations, according to a person familiar with the matter."

With this as background, it might be a better use of the Fourth Estate's time to ask the following questions:

How did Shkreli raise 100 percent of the $90 million Series A funding for a company with one product which, even at the highly inflated price of $750 a pill would generate less than $40 million in revenue?  

At Shkreli sought to drive down the share price of his company's stock in order to get exclusive marketing rights for a product at about a 90 percent discount. While Chief Investment Officer of MSMB He did the same thing in his effort to buy AMAG Pharmaceuticals in 2011 at a bargain basement price.  Here's what he said after badmouthing AMAG and driving down the share price:. “Over the past four years, the AMAG board of directors, presided over an 80% decline in the value of AMAG stock.   A letter the SEC sent to Shkreli reveals that the Turing CEO is very good a departing from the facts in explaining his investment activities.  
How do we know that Shkreli will not do the same with Turing?

A notorious short seller, is it possible that one way Shrekli is using to finance the offering is to use the price hike to short all other biotech stocks?

 Should the focus be on limiting the ability of short sellers and patent trolls to create drug companies that are essentially financed and designed to make money by a) bashing the core technologies of other companies as well as your own and b) buying up the marketing rights of one drug and using that, not the actual benefit of the drug, be the reason for huge price hikes?   

One other point worth further discussion.   In many cases health plans and PBMs have, by putting important medicines in the highest cost sharing tier, have in effect hiked drug prices by 5000%.   Isn't that wrong too? 

Finally, here's a good history of the way he wound up creating Turing. 

Shkreli, fresh off Retrophin firing, says Turing Pharmaceuticals will be public by year-end The Deal Pipeline March 5, 2015 Thursday"

The pain community is not happy with the CDC. And who can blame them?

Per the CDC website, that agency is publishing new guideline (sic) “for prescribing opioids for chronic pain. The agency is working for timely release of the guideline while ensuring that the development process:

  • Meets scientific standards
  • Includes expert consultation
  • Allows for appropriate stakeholders to provide input
  • Facilitates partnership development to enhance dissemination and uptake

But the agency’s definition of “transparency” has many up in arms. It's a travesty. Here’s what the leading pain organizations had to say to CDC Director Tom Frieden and Debra Houry, Director of the National Center for Injury Prevention and Control:

Dear Drs Frieden and Houry:

As members of U.S. chronic pain management professional associations and patient advocacy organizations, we, the undersigned, are profoundly invested in any and all efforts undertaken that could impact either the positive or negative outcomes of pain treatment. We have been anxiously awaiting CDC’s draft opioid prescribing guidelines, now revealed September 16th.

It was our expectation that the prescribing guidelines would have been

·      *  Developed in a transparent manner, consistent with best-known evidence

·      *  Or, where there is no evidence, by incorporating the common elements of long-accepted clinical expert consensus guidelines developed by a dozen organizations dedicated to the safe and effective treatment of patients with chronic pain

·      *  Consistent with those aspects of opioid medication prescribing and risk mitigation efforts that are actually supported with rigorous clinical trials, i.e. the FDA-approved indications for the full range of opioid formulations.

We were disappointed on all counts and now are deeply concerned that, not only are the CDC draft guidelines inconsistent with established best practices, they will potentially make it difficult for patients who rely on them for pain control to access them from clinicians who are clear on how best to use them.  

The CDC slides presented on Wednesday were not transparent relative to process and failed to disclose the names, affiliations, and conflicts of interest of the individuals who participated in the construction of these guidelines. The presenters refused to provide any information other than to read exactly what was written on the slides even when asked directly by audience members to disclose the processes and people who had developed these prescribing guidelines. Since CDC has traditionally not involved itself in developing and disseminating medication prescribing guidelines, and these recommendations are not consistent with current established guides for managing chronic pain with opioids, these process and participant questions are essential to understand.

A statement was made early in the presentation that it is acceptable and common practice to develop clinical recommendations even when there is a limited or non-existent base of evidence for (or against) the recommendation. In those cases, the standard is to convene expert clinicians with vast experiences in the condition and develop consensus around optimal approaches. CDC itself developed and published an analysis of existing guidelines that logically should have been the foundation for these new guidelines.

While there may be slight variances among organizations on specific guideline inclusions or recommendations, there is a broad conformity that extends beyond the focus of the new guidelines. By addressing only how to limit or avoid opioids, the new guidelines will inevitably result in fewer prescriptions overall - including those needed by patients with legitimate medical needs. Chronic pain advocacy organizations hear daily from increasing numbers of constituents who are not being able to access the opioid medications they’ve relied on to live with their chronic painful conditions. That is not an outcome that anyone involved in chronic pain and prescription opioid diversion and abuse wants but this guideline will produce.

In fact, it is CDC’s singular focus on prescription opioid diversion, abuse, addiction, and overdose over any improved understanding of chronic pain incidence, prevalence, trends, and optimal interventions that reveals within CDC an extreme imbalance in its own risk-benefit sensibilities when it comes to this class of medications. In evaluating new medications for approved uses, FDA requires safety and efficacy trials that all approved opioid medications have met. Detailed prescribing instructions are developed based on proven studies. Yet the new guidelines ignore the FDA’s prescribing expertise, recommending different maximum daily doses that appear in no guidelines or package inserts.

We call on CDC to immediately compile, analyze, and report any and all chronic pain data it possesses, managed with or without opioids. Certainly any health condition that impacts one third of our country’s population should, by definition, have a place of priority in CDC’s mission and mandate. CDC has a Center for Chronic Disease Prevention and Health Promotion that reports on arthritis as part of its annual chronic disease monitoring. Diabetes, interstitial cystitis, inflammatory bowel disease are all programs within this center that have, at their core, chronic pain components and may contain useful data. CDC also fields an Annual CDC/NCHS National Health Interview Survey that reports on severe headache or migraine, low back pain, and neck pain among adults. Obviously, a better understanding of how to effectively treat chronic pain should be an essential component to any treatment prescribing guideline. What CDC presented this week is not that.

If the new CDC guidelines reinforced existing recommendations of experts who agree there are tried and true approaches to safely and effectively using opioids to treat chronic pain, it would be a welcomed addition to clinical practices nationwide. Equally important, we need CDC to glean from its prescription opioid addiction and overdose data which cases actually involve chronic pain patients and which involve patients with active substance use disorder so we can help providers better differentiate the two.

The unmet challenge in chronic pain management with opioid treatment is to identify the conditions for which, and patients for whom, opioid use is most appropriate; the regimens that are optimal; the alternatives for those who are unlikely to benefit from opioids; and the best approach to ensuring that every patient’s individual needs are met by a patient-centered health care system. We need CDC to provide some context around the incidence and prevalence of undertreated pain and the related adverse consequences of undertreated chronic pain on all body systems. With these insights it may actually be possible to improve pain care rather than restricting one treatment based on perceived, not quantified, harms to legitimate patients.

We believe the most important outcome of treatment for chronic pain is pain control sufficient to enable people with pain to maintain a high level of patient-determined quality of life and functionality while avoiding or minimizing potential negative outcomes that could outweigh pain control benefits. We believe it is up to the patient, informed by a comprehensive and ongoing discussion with his or her providers, to decide if risks of opioid use apply to them and are acceptable to bear, when compared with the adverse physical, psychological, and quality of life impacts if pain cannot be adequately controlled without opioids. Our concern is ensuring that further stigma and physical harm to patients does not result from policies and guidelines that address only the risk of harm from inappropriately prescribed or used opioids, when what healthcare providers most require are affirmative strategies to help patients manage their pain.


Alliance for Patient Access*

American Academy of Pain Management*

American Cancer Society, Cancer Action Network, Inc.*

American Chronic Pain Association

Center for Lawful Access and Abuse Deterrence

Chronic Pain Research Group at the Clinical Pharmacokinetics Laboratory, University at Buffalo School of Pharmacy and Pharmaceutical Sciences*

Hospice and Palliative Nurses Association

Interstitial Cystitis Association

Massachusetts Pain Initiative

National Fibromyalgia & Chronic Pain Association

Pain Connection

Project Lazarus

The Pain Community

US Pain Foundation

Virginia Cancer Pain Initiative

* Participant in the FDA August 6 meeting

This unfair, unjust, and ill-considered CDC action must not stand.

Some good quotes from A Califf Regime: The Disruptor FDA, Industry Need, by the very savvy Donna Young of Scrip Intelligence --

The complete story (subscription only, sorry) can be found here.

If Robert Califf is confirmed as the next commissioner of the FDA – which most in the biopharmaceutical community are anticipating is all but assured – he'll be taking over an agency that's in the midst of some of the most complicated challenges it's ever faced, the resolutions of which have broad implications for drug and device makers.

The FDA is dealing with an inability to attract and retain the best and the brightest scientists, noted Ellen Sigal, chair of the nonprofit advocacy group Friends of Cancer Research (FOCR). "The salaries are terrible, hiring practices are convoluted and divestiture is complex," she told Scrip.

… Greg Daniel, managing director for evidence development and innovation at the Brookings Institution's Center for Health Policy and a fellow in economic studies at the Washington think tank, said another problem confronting the FDA is its need for consistent resources and funding to maintain and build on the advances the agency has made in developing new tools and refocusing on patients through new expedited development and review programs.

… Peter Pitts, president of the Center for Medicine in the Public Interest, a Washington think tank, and a former FDA associate commissioner during the George W. Bush administration, insisted Califf is the right leader and "precisely the right guy" to handle the knotty challenges ahead for the US regulatory agency – declaring the former Duke University professor's nomination was "the most important health care act the president has undertaken," even more so than getting the Affordable Care Act enacted.

President Obama’s nomination of Califf, announced on Sept. 15, "really is the biggest thing he's done to advance the public health," Pitts told Scrip. "I really believe that."

If confirmed as commissioner, Pitts said he thinks Califf, who he called an "action-oriented guy," will have an "immediate impact for many issues that need immediate attention" at the FDA – most specifically, precision medicine.

The fact that the past few times a new commissioner was being sought by Democratic and Republican presidents and Califf's name kept coming up as a potential contender demonstrates "he's highly qualified" and capable of doing the job, Pitts said, adding that it also shows that "occasionally, there is bipartisan sanity when it comes to health care issues."

What's most important, Pitts said, is that Califf is viewed as a well-respected scientist – both by regulators and industry alike.

Before joining the FDA this past February as deputy commissioner for medical products and tobacco, Califf had worked closely with the agency on several matters, including serving on its Cardiovascular and Renal Drugs Advisory Committee, "so his learning curve is not steep," Pitts said.

He said Califf also is well respected among regulators at agencies outside the U.S. – an asset that could aid the FDA and other regulatory bodies in harmonizing their review processes and rules, which could broadly benefit the drug and device industries.

But one of the greatest qualities Califf possesses, Pitts said, is his ability to innovate.

"He can take a theory and make it a practical reality," Pitts said, adding that he anticipates Califf to lead the FDA to be "partners in innovation" with industry through "entrepreneurial regulation."

"What that means is that Rob Califf can put the FDA at the center of the health care innovation ecosystem," he declared.

… "He's well known to be an innovator," Steven Nissen, head of cardiology at the Cleveland Clinic in Ohio, said about Califf. "He's been innovative in the design of clinical trials and has long been an advocate of finding ways to do clinical trials that are better, cheaper, faster. He's been somebody who has been outspoken about the fact that the approach we use for drug development is too costly and in some cases too long." Nissen said the current FDA is suffering from "years of stagnation."

"The FDA has not moved forward on any important initiatives during this period of stagnation," he argued. "And it needs a new look. It needs somebody to really come in and really shake things up."

Califf, Nissen said, is "capable of doing that … We really actually see the world pretty similarly."

Industry Ties

But while Nissen and Pitts showered praise on Califf, Public Citizen's Carome asserted President Obama's candidate to run the FDA was "bad news for patients and public health" because of the former Duke University professor's "long history of extensive financial ties to multiple drug and medical device companies."

But Pitts argued that "in my mind, the commissioner of the FDA should have an extremely up close and personal knowledge of industry to understand what's happening … I think anybody who knows Rob Califf knows he's not swayed by any financial interests," he said.

… Pitts, Nissen and Sigal all advocated for keeping Califf in the commissioner's role long after President Obama leaves office – declaring the FDA chief's job should be a five- or six-year term.

"I've long been an advocate for this not to be a political appointment," Nissen said.

The next critical path is the path to confirmation.

Good story in Congressional Quarterly on President Obama’s nomination of Rob Califf to be the next FDA Commisisoner.

Unfortunately, since CQ is a subscription-only service, I can only provide some snippets:

Califf, according to several former FDA officials, is a believer in new technology and involving the voice of the patient in the drug development process.

"He understands what the future of health care looks like," said Peter Pitts, who led FDA external relations during the George W. Bush administration.

Califf previously was a top official at Duke University's School of Medicine. During a 30-year career at Duke, he was in charge of the Translational Medicine Institute, whose goal is to speed up the development, testing and approval of drugs and devices.

At the time of his appointment, the FDA hailed Califf, a cardiologist, as "one of the top 10 most cited medical authors." Shortly before taking his FDA position, Califf oversaw a vast long-term study that revealed that a cholesterol-lowering drug could help prevent heart attacks in some patients who cannot tolerate a more common cholesterol-reduction method, statins.

But during his years at Duke, Califf developed close ties to players in the pharmaceutical industry. Some believe these relationships will be an asset for someone who needs industry buy-in for his agency's policies. If Califf is confirmed, Pitts said, it "means the FDA can be both the regulator of industry and its colleague in innovation."

The Senate Health, Education, Labor and Pensions Committee would hold a hearing on Califf's nomination.Sen. Lamar Alexander, R-Tenn., the committee chairman, said in a statement that the panel will move promptly on the nomination.

"Dr. Califf has impressive credentials," said Alexander. "The FDA affects nearly every American and needs the certainty of a strong leader. I look forward to hearing from Dr. Califf specifically on how we can move medical discoveries more rapidly through the FDA and other agencies and get safe treatments and drugs into Americans' medicine cabinets."

If Califf is confirmed, he may only have a little more than a year on the job. But FDA observers say that he's already worked hard to earn a rapport with different branches of the agency and policymakers.

Former FDA official Frank Sasinowski, now a consultant, said Califf will be able to "go into congressional hearings and people will understand that he has an appreciation of what it takes to drive innovation and get new therapies out to patients."

If you are a CQ subscriber, the full article can he found here.


Center for Medicine in the Public Interest is a nonprofit, non-partisan organization promoting innovative solutions that advance medical progress, reduce health disparities, extend life and make health care more affordable, preventive and patient-centered. CMPI also provides the public, policymakers and the media a reliable source of independent scientific analysis on issues ranging from personalized medicine, food and drug safety, health care reform and comparative effectiveness.

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