Euro-Vigilance

10/20/2015 07:40 AM |

Wither FDA?  Also, what about addressing incentives/responsibilities for enhanced physician/pharmacist/patient reporting?

From the pages of FDA News ...

EMA Releases Pharmacovigilance Program Update

Drugmakers must begin using a new centralized database for product safety update reports by mid-2016, the European Medicines Agency says.

The updated repository will also link the PSUR single assessment procedure number with products, making searches easier, and will allow for an automated two-way exchange between national authorities’ IT systems and the PSUR repository.

Use of the repository becomes mandatory on June 13, 2016. Until then, marketing authorization holders must continue to submit PSURs to national competent authorities.

The EMA is also finalizing revisions to its EudraVigilance Access Policy, which would give drugmakers greater access to adverse event reports, beginning in mid-2017. The agency’s management board is set to vote on the policy in December.

The EudraVigilance website will be updated in November with the publication of key documents such as the Stakeholder Change Management Plan, which details the IT and business changes companies need to make before reporting begins, the EMA says.

The EMA also plans to release a report this month on the launch of its Medical Literature Monitoring initiative, which allows drugmakers to easily search for information on adverse reactions associated with their products.

In addition, the EMA has launched an online invoice portal where companies can pay their annual pharmacovigilance fees. Under the fee program, which took effect in July, drugmakers must pay $70 for each product they market in the EU.

The agency has also updated its database of 500,000-plus drug products and is giving member states access to it. Drugmakers should enhance their in-house systems to allow for receipt of acknowledgment messages regarding new and modified marketing authorizations, beginning Nov. 4.

The changes were mandated in the 2012 pharmacovigilance legislation. View the EMA’s Pharmacovigilance Program Update at www.fdanews.com/10-14-15-PharmacovigilanceProgrameUpdate.pdf.   Read More & Comment...

NCCN Oncology Value Tool Devalues Hope and Medical Innovation

10/16/2015 12:50 PM |

Today, the National Comprehensive Cancer Network released a set of flash cards  to solve a drug cost problem that doesn’t exist by adding to a problem – insurers shifting the cost of cancer treatment to patients -- that does.  In so doing, NCCN undervalues hope and could inadvertently increase the rate at which cancer patients choose to give up hope when in fact medical innovation increases the reasons for such feelings. 

NCCN, like the American Society for Clinical Oncology (ASCO) has create a framework telling doctors and patients that in selecting treatments some medicines are worth more than others.

 NCCN, like ASCO, claims choosing which medicines are most affordable will address “the combination of increasingly unsustainable rises in the costs of cancer care, the accelerating pace of expensive innovations in oncology, and persistent hope for rescue in patients with life-threatening disease.”  Apparently, persistent hope is something we should discourage because saving a few dollars is more important. 

However, the assertion that cancer costs are unsustainable is untrue.  New cancer drugs are expensive no doubt.  Yet they account for only account for 0.7 percent of the $2.9 trillion we spend on health care.  Cancer spending has increased in 1995 from $42 billion to about $130 billion today.  But its share of total health spending declined from 4.7 percent to 4.4 percent during the same time period.  

In fact, new medicines reduce the cost incurred by a cancer diagnosis, for instance in part by reducing hospitalization.  In 1996 drugs were 3.7 percent of cancer spending and 62.4 percent went to hospitalization. By 2012, drug spending was 9.3 percent of cancer costs while the share going to hospitalization dropped to 41.3 percent.  During the same time period the life of expectancy of cancer patients increased, mortality rates declined by 20 percent and the number of cancer survivorship grew from 9.8 million to 13 million.  The NCCN flashcards ignore these cost and life saving gains.

To be sure, the out of pocket cost of cancer drugs has increased.  But the huge jump is caused by insurers and pharmacy benefit managers who force patients to pay up to 40 percent of the cost of a drug that two years only cost a few dollars a month. More recently, the percentage of health plans placing all drugs in the highest cost sharing tier has nearly doubled.

Capping cost sharing would require about people paying 50 cents more in premiums every month.  Yet NCCN accepts insurer  cost shifting as a fait accompli.  It forces doctors and patients to choose treatments, not based on value, but on the insurer imposed cost of a medicine, a cost that is often based on how big a rebate other medicines generate. 

Further, each NCCN flashcard measures one drug for one disease for an average patient.  But often drugs must be used in combination to achieve results. Indeed, each “tumor may embody more than 100 different diseases, and multiple subtypes of each tumor exist. Even if some of these tumors have things in common, the individual landscape of each patient may be very distinct.”

Finally, the flashcards are to be used, it seems, to discourage the persistent hope for rescue in patients with life-threatening disease.

Hope is a valuable thing. For example, AZT, the first HIV drug, showed no additional survival in clinical trials.  NCCN flashcards would deem them expensive but ineffective.  In the real world, the use of such medicines kept enough people alive until the next generation of anti-AIDS extended life by years. The flashcard negates that value.

A survey of patients who chose assisted suicide in Oregon show that since 1998 the number of people citing the cost of care as a reason for their decision jumped 77 percent.   To the extent that the NCCN flashcards reinforce the impact of insurer cost shifting and are skewed against persistent hope, they may contribute to an increase in cancer patients thinking there is no longer a reason of a value for living.  Let's hope not!
  Read More & Comment...

CDC and the Opioid Lunatic Fringe

10/15/2015 02:18 PM |

Interesting and well-sourced article on the continuing saga of the CDC’s opioid guidelines and the conflicts of interest of the Core Expert Group.

The article is titled, Dysfunction, Lobbying, and Conflict of Interest in the Debate Over Opioids and here’s one quote to whet your appetite:

“I’m sure everyone on the committee is an expert, but you need to have a variety of opinions, otherwise why even bother having the meeting in the first place,” said Pitts, whose responsibilities at the FDA included overseeing the formation of FDA’s advisory committees. Referring to PROP’s role in creating the guidelines, Pitts said, “When you basically take one group that is considered the opioid lunatic fringe and allow them to create the basis of your policy almost verbatim is inexcusable. It’s bad policy. It’s bad science. It’s poorly serving the public health.”

The complete article is well worth a read.

  Read More & Comment...

Price Controls Restrict The RIght To Live

10/15/2015 10:58 AM |

California Governor Jerry Brown signed a “Right to Die” bill into law lastweek.  Meanwhile, a state ballot initiative to impose price controls on medicines will insure that lots of people will take advantage of the law that otherwise would be alive.

That’s because price controls create shortages of important medicines, especially for cancer.   And price controls add months, if not years for the time it takes to get medicines to patients.  And price controls are always combined with steps to coerce patients to take cheaper medicines. 






1.  There is a right to die using an off-label combination of lethal drugs if you have a fatal illness.  There is no corresponding right to try an experimental treatment if you are dying.  You can get an experimental drug if the company making it will cover the cost. Setting prices artificially low even as the cost of developing new medicines increases means that the right to die will trump the right to try.

2. Similarly, we force dying patients to wait years for new medicines to become available.   In addition to Food and Drug Administration regulations, insurers and health systems demand evidence that a drug is worth it.  That demand makes people wait for many new medicines. Price controls are based on such ‘evidence’.  It is self evident that the unnecessary delays in access contribute to the desire to take one’s own life.  Price controls will and do affect the decision to die.

3. Finally, we are developing cost control mechanisms that reinforce the desire for assisted suicide.  Price controls are accompanied by so called treatment pathways limit the use of new medicines until people fail on older, often more toxic drugs with more side effects.   In an age of personalized medicine, it is possible to customize treatments to patients to extend life.  Yet most pathways use average response to one drug.  In turn, that average response – which will be far below what many people with an illness would experience – is used to measure the “value” of treatment.  

Most people choosing assisted suicide have cancer.  And most of the cancer patients who make that decision have tumors or cancer types that have shown the least progress over the past 20 years.   At the same time, the percentage of cancer patients choosing assisted suicide has declined since 1998 as new treatments emerge.  Indeed, in 1997 sixty-three percent of HIV patient assisted suicide, and 55% acknowledged considering physician-assisted suicide as an option for themselves.  In Oregon the number of HIV patients chose patients choosing assisted suicide went from from 10 in 1998 to 0 in 2014.   The key variable is access to new drugs – many of which were shown to provide benefits deemed not worth it by treatment pathways put forth by physician groups and insurers – that extend and improve life.   So by delaying access to new medicines that might be effective we are encouraging assisted suicide.

Finally, the Oregon survey shows that the reason for assisted suicide with the biggest increase since 1998 is financial implications of treatment.   The percent citing this cause jumped 77 percent.   By extension, eliminating financial burdens would eliminate assisted suicide. 

However, our health system is moving in the opposite direction.  It is shifting the cost of medicines that offer hope to patients.  In many cases insurers are increase the effective price of medicines by more than the 5000 percent increase that has been a source of outrage.  Under price controls, insurers and government health programs would not be obliged to cover anyt medicine it believes is too expensive. What’s more, rather than fighting to eliminate that burden with copay limits, the leading cancer doctor and provider trade groups have made the insurer-imposed cost to the patient a key reason dying patients should choose one treatment or another or no treatment at all.  

A system that delays access to new treatments, underestimates survival and deliberately exposes the dying to the cost of the potential most effective treatments and then hits the patient over the head with the expense (instead of protecting them from it) essentially makes it easier for the the sick and disabled to die. As my colleague Peter Pitts has noted, in Oregon Medicaid denies coverage for certain cancer treatments for patients that have been deemed “too” sick, haven’t responded well to previous treatments, or can’t care for themselves.
Oregon state bureaucrats are severely restricting access to care and dooming potentially thousands of local patients to a premature death with medicines the state will gladly provide free of charge. 

We have a health system that is turning the right to die into a duty to die.  Price controls will make it virtual requirement to do so.  Read More & Comment...

CDC and Opioids. Conflict? What Conflict?

10/14/2015 09:04 AM |

Much debate over the manner in which the CDC handled conflicts of interests with its opioid guideline development team.

And there’s going to be a lot more.

The Annals of Internal Medicine has just published its Principles for Disclosure of Interests and Management of Conflicts in Guidelines.

In the very first paragraph, the guidelines warn against …

 "Intellectual COIs, including attachment to ideas or academic activities that create the potential for an attachment to a specific point of view." Specific examples of this are listed as, “community standing,” “personal convictions or positions,” leadership or board committee memberships” and, “Leadership or board, or committee memberships.”

And who appears on the CDC’s Core Expert Group? 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.

On every count the CDC fails the test of intellectual conflict of interest. According to the CDC, they agency “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.

The complete guidelines from the Annals of Internal Medicine can be found here. It should be mandatory reading at the CDC.

  Read More & Comment...

Is Priority Review for sale to the highest bidder?

10/12/2015 07:42 AM |

From the pages of Fierce Biotech …

The FDA is lukewarm on those hyper-valuable vouchers for fast drug reviews

Big Pharma has been willing to pay hundreds of millions of dollars for a shortcut to FDA approval, buying up priority review vouchers created to incentivize new drugs for neglected diseases. But the agency seems less than enthusiastic about honoring its end of the bargain, with one top official expressing concerns about how the voucher program might harm the FDA's core mission.

In an interview with Pharma & MedTech Business Intelligence, FDA Office of New Drugs Director John Jenkins said the agency's long-held problems with priority review vouchers have been "amplified" as more and more companies line up to redeem them. And the market value of the vouchers has skyrocketed over the past year, with one going for $350 million in August, suggesting the issue isn't going away.

The voucher program, created in 2007, works like this: Any drug company that wins approval for a new drug that treats a rare pediatric disorder or neglected tropical disease is given a one-time coupon, which, when redeemed, shortens the FDA review process from 10 months down to 6. And, in a move designed to encourage R&D into such under-served diseases, winning companies can sell their vouchers to anyone they please and at whatever price.

But what's not negotiable is that 6-month timeframe, and that's what worries Jenkins. "In effect, these programs allow sponsors to 'purchase' a priority review at the expense of other important public health work in FDA's portfolio," he told PMBI. The FDA has a finite amount of time and resources available at any given time, and allowing one company to cut in line inevitably affects the agency's ability to do its job elsewhere, he said.

And the universal applicability of a priority review voucher could also create problems, according to Jenkins. A drugmaker could--as Sanofi did--use its coupon on a primary care treatment that would be used by millions of patients. Such drugs require multiple large clinical trials to support approval, and thus their applications are complex and time-consuming. "Reviewing such an application in 6 months is very challenging," Jenkins told PMBI, and the voucher program does not provide any additional staff to follow through.

Despite regulators' concerns, however, the program is a hit with industry, which is paying more and more for the privilege of a quick review.

The first voucher to change hands came from BioMarin, which sold the coupon to Sanofi and Regeneron last year for $67.5 million, helping the pair leapfrog Amgen in the race to launch a new class of cholesterol treatments. Months later, Gilead Sciences paid $125 million for Knight Therapeutics' voucher in hopes of accelerating its HIV pipeline, followed by Sanofi splurging $245 million for Retrophin's priority ticket and AbbVie promising $350 million to United Therapeutics for the same asset. Last month, AstraZeneca paid an undisclosed sum for a voucher of its own.

Here’s the full Jenkins interview.

  Read More & Comment...

Donald Trumps PBMs?

10/09/2015 02:40 PM |

Pharmacy benefit managers make money by denying care

By Peter J. Pitts

Special to the Mercury News

Donald Trump, Hillary Clinton and Bernie Sanders all think that healthcare is too expensive. But they're looking in the wrong places for savings. In 2012, the CEO of the nation's largest pharmacy benefit manager, Express Scripts, earned about $1 million every week.

PBMs can afford such rich compensation because they increasingly refuse to pay for patients' medicines. In 2016, Express Scripts will deny coverage to 124 medicines -- up from 95 drugs this year. America's second largest PBM, CVS Caremark, announced that it will banish an additional 14 drugs from its 2016 list of covered medications, in addition to the 66 forbidden medicines in 2015.

By refusing to cover specialized drugs, Express Scripts and CVS Caremark aren't just denying patients access to lifesaving medication. They're also driving up healthcare costs for patients.

PBMs design and maintain drug formularies, the lists of medications available under particular health plans. Their influence is massive because PBM-administered plans cover more than 210 million Americans insured through employers, unions, or government programs like Medicare Part D.

PBMs can play a valuable role as middlemen in the healthcare system. They streamline the drug purchasing process by supplying thousands of pharmacies and insurers with prescription contracts. They also hold healthcare spending in check by using their immense purchasing power to negotiate large discounts from pharmaceutical manufacturers. Their profit comes from pocketing any rebates they extract from drug makers that they don't pass on to pharmacies and insurers.

However, the largest PBMs -- particularly Express Scripts and CVS Caremark -- increasingly abuse their role and pad their bottom lines by simply refusing to cover certain lifesaving drugs.

CVS Caremark, for example, recently took to the Journal of the American Medical Association to promote the use of cheaper statin medications rather than specialized new drugs that can cut "bad" LDL cholesterol levels in half. Doctors have called the new medicines a "game-changer" in the fight against coronary artery disease.

Innovative drugs are often the groundbreaking ones that revolutionize treatment of serious diseases. Consider Sovaldi, which PBMs have attacked as "unreasonable" due to its $84,000 price tag. Yet the drug cures 90 percent of hepatitis C patients in a 12-week treatment with vastly reduced side effects. Previous treatments took up to a year and cured only half of patients.

Last year, pharmacies sued Express Scripts over its "scheme to deny all claims" for certain customized medications. "The scheme is forcing patients to go without treatment," the suit stated, "jeopardizing their health and causing bodily harm, or forcing them to pay out-of-pocket sums that they may or may not be able to afford for basic healthcare needs that have been prescribed by their doctors."

Without medicine, many patients grow sicker and require more expensive care in hospitals and nursing homes.

Prescriptions are almost always the most cost-effective treatment option. The Congressional Budget Office estimates that a 1 percent increase in prescription use by Medicare beneficiaries causes Medicare's total medical spending to fall by about one-fifth of 1 percent.

So in effect, PBMs are passing the buck to insurers and government healthcare programs, which are on the hook for pricier treatment regimes.

Most people would find it shameful to withhold medications from sick patients, especially since doing so raises the financial burden on consumers and taxpayers. Unfortunately, America's pharmacy benefit managers are adopting this callous strategy with increasing frequency.

  Read More & Comment...

Mountain Due

10/09/2015 07:49 AM |

I’ve just returned from the glorious Mountain West (Salt Lake City to be precise) where I attended the Utah Employer Healthcare Summit.

One of the panels I attended, “Healthcare Consumerism,” included a regional exec from Aetna. He bragged on his firm’s “commitment to transparency.” As an example he described their new customer app. I commented that giving people access to their own data wasn’t transparency. That got things going. The next question came from a physician who asked why they don’t share information about the discounts they get from drug manufacturers. His response was classic, “because it’s confidential.”

The physician was not assuaged. Quite the contrary.

The issue of the role payers play also became a central theme on the panel I participated on, “The $84,000 Pill.” One of my main points was that payers regularly receive significant discounts on medicines – and then don’t pass along the savings to consumers. The audience was largely comprised of employers and I made sure they understood that the same issue holds true for PBMs and their consumers – employers.

Allow me to share one telling moment. Another panelist, an executive from a large regional PBM, was explaining why they can’t afford “$84,000 for Sovaldi.” I (politely) interrupted him to ask, “Many large payers are getting upwards of a 50% discount on Sovaldi.” He shot back, “We’re only getting a 38% discount.” “Well,” I said, “then maybe you should stop talking about an $84,000 pill and start talking about a $52,000 treatment that cures the patient 90+ percent of the time.” His snappy comeback? “It’s not that simple.

“The truth,” as Oscar Wilde quipped, “is rarely pure and never simple.”

  Read More & Comment...

CDC's Flawed Opioid Efforts. Attention must be paid.

10/08/2015 10:38 AM |

When it comes to the CDC’s new opioid guidelines, attention must be paid -- immediately and publicly. This is the message from a growing constituency of physicians, patients and policy experts concerned and upset about both the CDC’s conflict-ridden, secretive process and, even more importantly, the guidelines themselves.

Regarding the CDC’s lack of transparency, consider first the comments of the California Medical Association:

It is deeply concerning that the details behind the 12 recommendations are being made available to some unknown organizations and individuals for review and comment, but not to the general public. The information available to the public was so limited and the time to comment so brief, that it created the perception that the end result has already been determined. Further, it is inappropriate for a public agency to limit the stakeholders from whom they will accept comments. All entities should have the same opportunity for review and comment. In addition, an anonymous summary of comment is also not part of a transparent public process, as it allows for potential CDC reinterpretation of the comments. The public must also be able to assess the potential biases and the opioid prescribing expertise for those involved in the creation of the guidelines.

And from the American Cancer Society:

We have concerns that the attempts to solicit public input on the draft guidelines were cursory and did not allow adequate opportunity for thoughtful responses. While a public webinar was held to discuss the recommended guidelines, it was not well advertised and many interested parties were denied access because the webinar lacked sufficient capacity. Further, only a brief summary of each of the recommendations was shared, with no supporting documentation to provide evidence, context, or insight into the process. The public had 48 hours to comment, a rather abbreviated time period when compared to typical 30-90 day comment periods for similarly impactful proposed policies by the administration. By legal definition the guideline is not a proposed regulation subject to the Administrative Procedures Act, but clearly the intent of CDC is that the guideline be distributed to and adopted by state public health entities and certifying organizations as if it had the legal authority of a regulation. Given the potential public impact of the proposed guidelines, CDC should provide more complete information to the public regarding their draft guidelines and provide commensurate opportunity for input.

Of greater importance are the issues with the proposed guidelines themselves.

Per the California Medical Association:

CMA is particularly concerned about the impact in our state, where the Medical Board of California (MBC) recently conducted a year-long, fully transparent public process that produced well-balanced opioid prescribing guidelines (see enclosure). Health care practitioners who treat pain in diverse settings were extensively engaged and given ample opportunity to provide feedback. The detailed guidelines reflect the realities of patient care and underscore the extraordinary complexity in treating pain. For example, to stress the need for flexibility, the MBC guidelines state in the preamble that “Medicine is practiced one patient at a time and each patient has individual needs and vulnerabilities” and the language in the MBC document reflect this statement. The guidelines also include an extensive discussion about the nature of pain and the treatment of pain that was not reflected in the CDC recommendations. We are also concerned because the CDC recommendations include a ceiling dose that is in conflict with California’s guidelines, which creates confusion and could have legal repercussions.

And the American Cancer Society points to the fact that the guidelines aren’t based on solid evidence:

CDC purported to follow a widely used framework for producing evidence-based recommendations known as GRADE (Grading of Recommendations, Assessment, Development and Evaluation) to create the proposed guidelines. In reality, however, CDC appears to have deviated significantly from the established methodology, calling into question the integrity and validity of the ensuing recommendations. Seven of the 12 recommendations were based on “very low quality of evidence” and five of the 12 on “low quality of evidence,” yet six of the seven recommendations with evidence rated “very low” and all of the recommendations with “low” evidence ratings were designated as “strong” recommendations. The GRADE process ordinarily permits this discordance only in exceptional circumstances, and this stark departure from GRADE methodology was done without associated justification. The rationale statements appeared to rely heavily on expert opinion, but this was not explicitly acknowledged.

Further, the ACS asks a crucial question, why has the CDC factored in cost in the guidelines development process?

We take strong exception to the use of cost data as an input to the guidelines. The costs highlighted in the document deal with non-medical use, abuse and overdose of opioids, but no mention is made of the costs due to chronic pain. Further, while costs may be a valid consideration in the context of GRADE methodology, it is wholly inappropriate for the government to use cost, rather than efficacy, to suggest restricting access to treatments that patients pay for themselves through copays and insurance premiums.

Bottom line:

CDC’s recent efforts are not appropriate, nor transparent … We strongly urge that CDC provides CMA and others with a reasonable opportunity to provide meaningful comment on such a critical issue.

-- California Medical Association

We share the goal of reducing inappropriate use and adverse events related to opioids, but we also have grave concerns about unduly restricting access to appropriate and effective pain management for individuals with cancer and other chronic conditions. We are concerned that the draft document does not reflect the appropriate weighing of benefits and harms at the individual and population levels, a fundamental element of rigorous guideline development. The process that the CDC followed departed from reliance upon evidence and methodological rigor, as well as accepted standards of transparency. We strongly suggest that CDC withdraw its draft guideline and instead focus on generating additional data to inform future guidelines as well as ongoing educational efforts on harm and abuse prevention.

-- American Cancer Society

The full comments from the California Medical Association and the American Cancer Society are worth a careful read.

An opaque and inappropriate process results in flawed and inappropriate guidelines. Attention must be paid.  

  Read More & Comment...

The Latest Gems on REMS

10/07/2015 01:31 PM |

From the fine folks at RAPS ...

FDA Launches Pilot to Standardize REMS Information for Easier Systems Integration

The US Food and Drug Administration (FDA) has announced a four-month pilot to make Risk Evaluation and Mitigation Strategies (REMS) easier to share and integrate with existing pharmacy and health information systems.

Background

With the passage of the 2007 Food and Drug Administration Amendments Act, FDA was granted the authority to require manufacturers to develop REMS for new and approved products.

These plans are intended to enable companies to better manage known or potential risks their products carry, and may be required as a condition for approval.

Then in 2012, as part of the Prescription Drug User Fee Act (PDUFA) reauthorization, FDA agreed to take steps to "measure the effectiveness of REMS … standardize REMS, and with stakeholder input seek to integrate REMS into the existing and evolving healthcare system."

To fulfill these commitments, FDA in 2013 held a public stakeholder meeting on standardizing REMS, followed by an expert workshop which evaluated "current approaches in the design, development, implementation, and assessment of REMS, limitations of existing methods for the design of REMS programs, and existing approaches to identify, evaluate, and mitigate risks that can inform REMS design."

Pilot Project

Following the stakeholder meeting and expert workshop in 2013, FDA developed four "priority projects" related to REMS to tackle in the coming years.

Today's pilot announcement marks the launch of one of these priority projects, which is intended to integrate REMS into Structured Product Label (SPL) format, which will make it easier for these documents to be integrated into pharmacy and hospital IT systems.

FDA says that stakeholders have "expressed concern that information about REMS materials, tools, and requirements are not communicated … in a clear and consistent manner," and that "REMS materials and requirements may be difficult to locate."

The agency also says stakeholders have reported "difficulty integrating REMS materials and procedures into their existing … systems."

FDA says it believes this pilot will "address many of the concerns … regarding REMS because SPL information can be easily shared and made available online." The agency also says both it and manufacturers are already well-versed with SPL, which will make transitioning to the format fairly straightforward.

FDA says it is looking for no more than nine volunteers to take part in the pilot and asks interested parties to apply by 7 December 2015. The pilot project is slated to run from 6 October 2015 through 3 February 2016, and may be extended if necessary.

Federal Register

  Read More & Comment...

The Expanded Access Ecosystem

10/06/2015 09:11 AM |

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.

  Read More & Comment...

Bernie's Papal Indulgences

09/29/2015 10:39 AM |

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.”

  Read More & Comment...

Patient-Focused Drug Development: Is the Past Prologue?

09/28/2015 09:23 AM |

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.

  Read More & Comment...

There's a new Cop (Cha) in Town

09/25/2015 04:15 PM |

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

  Read More & Comment...

Why people don't trust drug makers

09/25/2015 06:55 AM |

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.

  Read More & Comment...

Opioids and Sunshine at the CDC

09/24/2015 07:45 AM |

  Read More & Comment...

Turing is NOT Pharma

09/22/2015 02:31 PM |

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 Street.com 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"
 

  Read More & Comment...

CDC gets it transparently wrong on opioids

09/21/2015 01:42 PM |

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 16^th.

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.

Sincerely, 

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.

  Read More & Comment...

The Califf Regime and the Critical Path to Confirmation

09/17/2015 09:15 AM |

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.
 

  Read More & Comment...

RE: Rob Califf -- CQ on the QT

09/16/2015 09:41 AM |

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.

  Read More & Comment...