21st Century Cures: PDUFA Jr. or PDUFA Plus?

12/07/2016 02:03 AM | Peter Pitts

The 21st Century Cures Act provides a legal foundation for regulatory innovations including approving supplemental indications based on real-world evidence and approving antimicrobial drugs for limited populations. The bill also would help FDA recruit and retain staff by creating mechanisms for it to pay salaries that are competitive with those offered in the private sector.

Other key provisions include:

* Real World Evidence. Require FDA to establish a framework for use of real-world evidence to approve supplemental indications and satisfy post-approval requirements. Timeframe: Within 2 years

* Healthcare Economic Information. Clarify ability of manufacturers to discuss pharmacoeconomic data with payers, formulary committees and others. Timeframe: Immediate

* Limited Population Pathway. Allow limited approval of antimicrobial drugs for life-threatening infections; require labeling and advertising to include “Limited Population” language. Timeframe: Immediate

* Summary Level Review. Allow approval of new indications based on data summaries from sponsors (sponsors must also submit full data). Timeframe: Immediate

* Accelerated Approval for Regenerative Advanced Therapies. Create regenerative advanced therapy designation that allows accelerated approval and use of clinical evidence, clinical studies, registries or other real-world evidence to satisfy post-approval requirements; require FDA to explain decision not to grant regenerative advanced therapy designation. Timeframe: Immediate

* Qualification of Drug Development Tools. Establish review pathway for biomarkers and other drug development tools to shorten development and reduce failure rate. Timeline: Draft guidance within 3 years; final guidance 6 months after end of comment period

* Reauthorization of Program to Encourage Treatments for Rare Pediatric Diseases. Reauthorize the pediatric rare disease Priority Review voucher program until 2020; a drug designated by Sept. 30, 2020 could receive a voucher if approved before Sept. 30, 2022. Timeframe: Immediate

* Silvio O. Conte Senior Biomedical Research Service. Increase senior biomedical research service positions to 2,000 from 500, allow FDA to deploy biomedical research service members for product assessments, increase maximum salary to president’s salary. Timeframe: Immediate

* Hiring Authority for Scientific, Technical, and Professional Personnel. Allow FDA commissioner to set salaries for scientific, technical, or professional positions at up to the president’s salary. Timeframe: Immediate

* Patient Experience Data. Require statement upon drug approval about FDA’s use of patient experience data collected by patients, caregivers and their representatives; disease research foundations; researchers; and drug manufacturers. Timeframe: 180 days

* Patient-Focused Drug Development Guidance. Require FDA guidance on how to collect patient experience data for use in regulatory decisions, how patients can submit proposals and how FDA will respond to them, and how FDA plans to use such data. Timeline: Initial plan in 180 days; draft guidance within 18 months; revised or final guidance 18 months after end of comment period

* Expanded Access Policy. Require companies to have publicly accessible compassionate use policies for investigational drugs treating serious or life-threatening conditions. Timeline: 60 days

On the down side, the $500 million of funding is not mandatory. Stay tuned.

For an excellent recap of the legislation, have a look at BioCentury’s Steve Usdin’s excellent article. Per Usdin, “The political process has created a consensus bill that lacks the kind of paradigm-shifting changes its authors promised. But Cures would produce real, though modest, forward motion in several areas that are important for translating scientific advances into new therapies.”

And, importantly, “Critics of the 21st Century Cures Act have warned that it would erode approval standards by allowing FDA to approve drugs based on anecdotal evidence. This is a huge exaggeration. What Cures would do is start FDA down the long road toward relying on real-world evidence to support selected regulatory decisions.”

Bravo.  Read More & Comment...

Two Patients Overcome Illness To Take On ICER

11/20/2016 11:48 PM | Robert Goldberg

The best way to measure the value of medical progress is to find out what people fighting serious chronic illnesses do as they get stronger and healthier.   

When two people going on different journeys in overcoming potentially life threatening diseases and wind up on a common mission --  to battle against health care policies that deny well-being to others --  you know that value cannot be defined simply as what saves health insurers money. 

Don Wright was diagnosed with multiple myeloma in 2003 just ran his 100th marathon.   He has been taking one pill a day since then to keep the disease in check and now, with the latest addition of another medicine, he is making his centennial run without missing a stride.   When he not running or practicing law, Don provides other people with cancer support and guidance.  

Dani Yevsa was diagnosed with psoriatic arthritis. Denied newer medicines by her insurer, she had to try older drugs first. Unable to move, let alone work, her husband quite his job to care for their four children.   To get the care and medicine they needed to stay alive, went on welfare.   Medicaid where she was forced to fail on three treatments that made her sicker, not better.   
She is finally on medications her doctor prescribed.  

Both Don and Dani took different approaches to the same path.  They are making thousands of patients around America about an insurance funded organization called The Institute for Clinical and Economic Review (ICER).  ICER states it is “a trustworthy, independent source to help assess how valuable a new drug really is.”  And it claims its goal is to make innovative drugs affordable to patients and insurers.  

Except that ICER has decided Don and Dani should only get the older drugs that would have left him disabled or dead.

ICER is deciding for Don, Dani and millions of other patients how much their lives are worth, not the other way around.  And ICER has decided that the benefits new drugs provide healthy people are MORE valuable than life-years gained by those who are chronically ill or disabled. Similarly, Dani and Don are worth less according to ICER’s economic assumptions, because they are less likely to get as much benefit from medicines than people with more treatable conditions.  And finally, ICER assumes that future benefits are less valuable to Dani and Don than to others.   

So it’s no surprise that ICER concludes every new medicine isn’t worth paying for unless they are deeply discounted off retail price and save money by reducing the use of other medical services.  

ICER responds that it’s trying to find prices that patients can afford first and foremost.  But the deeper discounts they recommend don't make medicines affordable or free up cash. In the real world of how PBMs and insurers price drugs, the savings go to PBMs and insurers, not patients. At the same time, insures overcharge customers for prescription drugs by making them pay up to 50 percent of the retail price of the drug.  ICER has issued over a dozen studies and never once wrote or spoke about passing these savings to the patients.  

Additionally, ICER suggests that to save even more money, insurers limit the number of people who have access to these new life extending medicines.  ICER believes that spending more than $900 million a year on a new medicine should set off alarm bells that strong action – capping how many people can get the novel treatments – must be taken.   For psoriasis, ICER concludes that health plans can only cover about 35 percent of the 183000 people diagnosed with psoriasis could be treated with before potential budget impact reaches $904 million.  For multiple myeloma, ICER caps access at 25 percent.

That means they before they can get these new drugs, if ever, they have to take older drugs and get sicker.   That means, over 5 years, ICER would deny 44000 people with myeloma a second and third chance at life and cost 88000 life years. Over the same time period, given the mortality rate associated with older psoriasis drugs, about 52000 life years would be lost.   Dead patients cost nothing. 

Don and Dani and others already pay thousands in premiums and taxes only to be denied new medicines based on the kind of rationalizations ICER produces. They have ICER in their sights because the more its recommendations spread, the more money health plans make at the expense of people they often impoverish when they are most vulnerable. 

ICER defines value as what’s most profitable for PBMs and health plans. It devalues what makes medical progress so important: When you’re seriously sick, it’s hard to plan or hope. Our dreams our diminished and deferred.  We are forced to forsake our full potential. 

ICER claims such benefits can’t be counted because they can’t be quantified.  I think we can easily measure the value of medical progress: Value is what Don has achieved, what Dani has fought for and the path they are forging for everyone who is or may be forced to fight disease  Read More & Comment...

CREATES Act should be created equal

11/15/2016 08:28 AM | Peter Pitts

From today's edition of the Washington Times:

Taking risks with drug safety

Congress must remedy the Creates Act before passing it

Over 60 percent of Americans want the government to take action to lower prescription drug prices, according to a new Kaiser Family Foundation survey. Congress, for once, is listening to voters.

Lawmakers are pushing forward with the Creating and Restoring Equal Access to Equivalent Samples (Creates) Act. The bill’s sponsors hope a series of new legal provisions will make it easier for drug companies to introduce generic alternatives, thus spurring competition and bringing down prices. The bill is well-intentioned. Unfortunately, it’s also worded extremely poorly. Instead of bringing generics to market sooner, the bill could endanger patients’ lives and encourage costly, needless litigation.

The proposed law would address conflicts between innovator drug companies and their generic competitors. To protect consumers, the Food and Drug Administration requires that new drugs undergo a series of clinical trials to prove their safety and effectiveness before entering the market.

Generic drugs must also complete clinical trials, but only to prove they’re clinically similar to the already-approved brand-name drug. The generic drug creation process inherently requires that manufacturers obtain brand-name drug samples from innovators for comparative testing.

Many drugs are so potent, or have such dangerous side effects, that the FDA requires drug companies to develop and abide by specialized safety protocols called “risk evaluation and mitigation strategies,” when selling or dispensing these medicines.

For example, Soliris, a drug used to treat rare blood disorders, can potentially cause dangerous bacterial infections in the bloodstream. Because of these possibly fatal side effects, the FDA-approved risk evaluation and mitigation strategy requires that only specially certified physicians can prescribe Soliris, and that patients must be given an information card to help them recognize early warning signs of an infection.

Here’s where it gets complicated. Generic drug companies are accusing brand-name manufacturers of dragging out negotiations regarding these risk evaluation and mitigation strategies to avoid handing over drug samples. Without the samples for comparative testing, generic manufacturers can’t enter the market. And without competition, the brand-name manufacturers get to keep selling their medicines at inflated prices, even after the patent has expired.

That’s why some in Congress want to pass the Creates Act. The bill would allow generic drug manufacturers to sue brand-name manufacturers if they fail to hand over their drug samples for testing within 31 days, or if the companies do not reach an agreement on shared risk evaluation and mitigation strategies for risky drugs.

That sounds reasonable. Nobody wants brand-name companies to drag their feet and keep prices higher longer than necessary. But the Creates Act’s language is so imprecise that it could lead to potent medicines falling into the wrong hands, without adequate safeguards for patients.

The bill strips the FDA of its watchdog role. Under the proposed law, generic manufacturers aren’t required to outline testing and safety protocols for the FDA to approve. Even if a generic drug maker’s proposed risk evaluation and mitigation strategies are inadequate, the FDA has no authority to reject or halt the transfer of medicines to the generic company for testing.

The experts at the FDA would have no choice but to approve the transfer within 90 days, even if they think doing so would put patients in danger. The Creates Act would also be a trial lawyer’s dream come true.

Poorly worded liability provisions subject innovators to unfair legal risk. Generic drug companies often obtain brand-name drug samples and ship them off to third-party research firms to perform clinical trials. If the third party is negligent with the samples, patients could get hurt. Under the bill’s terms, patients would be able to sue the brand-name drug company, even though it had no control over the testing or safety protocols.

The bill also lets generic drug companies sue innovators for not handing over samples within 31 days of a request, even if both companies are actively negotiating the terms of the sample distribution and safety protocols.

And though the proposed law requires innovators and generic companies to strike transfer deals on “commercially reasonable market based terms,” the law doesn’t clarify what that means. Such subjective wording is music to trial lawyers’ ears.

Congress deserves praise for trying to bring generic medicines to market faster, thereby relieving consumers from high drug prices. Yet good intentions don’t change the fact that the Creates Act, as constructed, is deeply flawed. Congress could help consumers by reworking the law to ensure it stops isolated bad behavior without gutting safeguards for patients or enabling unscrupulous trial lawyers to file costly, pointless suits.

Peter J. Pitts, a former FDA associate commissioner, is the president and co-founder of the Center for Medicine in the Public Interest.
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The PBM Sky Hook

11/08/2016 03:35 PM | Peter Pitts

From today’s edition of the East Bay Times …

Patients threatened by new drug coverage limits

Kareem Abdul-Jabbar’s toughest fight wasn’t on a basketball court.

In his early 60s, the six-time NBA champion was diagnosed with leukemia, the deadly blood cancer. Fortunately, Abdul-Jabbar had access to state-of-the-art medications, including the advanced drug Tasigna, which paralyzed his cancer cells and prevented further growth. Today, eight years after his initial diagnosis, Abdul-Jabbar is thriving and cancer-free.

Unfortunately, many of today’s leukemia patients won’t be so lucky. CVS Health, the nation’s second-largest pharmacy benefit manager that oversees 65 million Americans’ drug plans, recently rescinded coverage for Tasigna –— and 130 other specialty drugs.

As a result, millions of people could be denied access to drugs that could save their lives. Instead of prescribing the medicines best-suited to patient needs, physicians will be forced to recommend lower-quality treatments.

Pharmacy benefit managers, or “PBMs” for short, administer the prescription drug plans used by health insurers and employers. In recent years, these organizations have gotten stingy about which drugs they cover.

Back in 2012, the nation’s largest PBM, Express Scripts, excluded no medicines from its list of covered drugs, while CVS Health left off about 30. Today, they exclude more than 200, including an array of popular treatments for arthritis, Hepatitis C, and various skin conditions.

PBMs have also stopped paying for cutting-edge cancer treatments. In addition to Tasigna, CVS won’t cover the revolutionary prostate cancer treatment Xtandi. Meanwhile, Express Scripts just stopped covering Zyclara, a cream that can help prevent skin cancer.

PBMs are restricting drug access in other, more devious ways as well.

CVS is also steering patients away from ultra-complex “biologic” drugs, forcing them to switch to lower-cost treatments the company claims are medically equivalent. But in many cases these less expensive therapies, known as “biosimilars,” aren’t approved by the FDA to be interchangeable with their brand name alternatives.

Consider one study that compared the effectiveness of a Crohn’s disease treatment and its biosimilar. An alarming eight in 10 patients who took the biosimilar required a hospital readmission for additional treatment, compared to only one in 20 who took the original drug.

Despite these disturbing results, PBMs are comfortable forcing patients to use biosimilars and generic medications. That’s because their only concern is bringing down short-term drug spending — even if those savings come at a cost to patients’ well-being.

Ironically, this strategy will end up raising health care costs in the long-run. If doctors can only prescribe less-effective treatments, folks will get sicker, be hospitalized more frequently, and require more expensive care. That demand will drive up overall healthcare costs and overwhelm doctors and hospitals with waves of new patients.

That doesn’t matter to PBMs, though. A dollar saved by avoiding top-notch drugs is a dollar that goes into PBMs’ pockets — even if the patient becomes sicker on less effective treatments and racks up much larger hospital bills for insurers and patients to pay down the road.

PBMs coverage denials are a deadly prescription for America’s patients. By shrinking coverage for cutting-edge treatments, PBMs are forcing sick people to use substandard drugs. It’s about time patients mount a full-court press against this callous behavior.

Peter J. Pitts, a former FDA associate commissioner, is president of the Center for Medicine in the Public Interest.  Read More & Comment...

Alta Vista

11/04/2016 08:14 AM | Peter Pitts

As they say, everything you read in the newspaper is true -- except for those things you know about personally.

According to the latest report from the Altarum Institute, “moderate 2016 health spending growth continues a slow downward trend.” Unfortunately this doesn’t fit the narrative of those who want to talk about runaway trains – especially for pharmaceuticals.

Here are the numbers: Hospital spending represents 32% of American healthcare spending, 20% goes to physician and clinical services, 15% goes to “other health spending,” and 10% is for prescription drugs.

If the media had covered this story -- which they have not -- the headline would have been, "Pharmaceuticals represent 10% of American healthcare spending. A dime on the dollar. A smaller percentage than almost every nation in Europe."

And here’s the subhead – Spending on pharmaceuticals is growing at a slower rate (under 4%) than either hospital (just under 5%) or physician costs (just over 5%). This breakdown is based on the Bureau of Economic Analysis monthly spending data, including its most recent update released on August 29th of this year.

While pharmaceutical spending seems to be the only issue of interest to the media and politicians, the Altarum account isn’t the one they’re telling. Almost every story and every speech on the drug sector focuses on price without the context of value, using a few bad actors to represent the entire industry. Unfair? Sure -- but life is unfair. There is, however, no excuse for slanted stories and untrue, accusatory political oration.

Disease is the enemy. Practicing physicians know this, but their professional association – the American Medical Association – seems in need of some education. The AMA’s new program, “truthinrx.org,” is entirely silent on the actual metrics of healthcare spending and the value of pharmaceutical innovation. Ignorance is not bliss.

Healthcare innovation saves lives, saves money, promotes economic growth, and provides hope for hundreds of millions of people (both patients and care-givers) in the United States and around the world. It deserves respect – or at least honest reportage.

Does this sound naïve? Perhaps, but as Schopenhauer said, “All truth passes through three stages. First, it is ridiculed. Second, it is violently opposed. Third, it is accepted as being self-evident.”

The complete Altarum report can be found here.
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Insurers to CMS, Congress: We Want More Rx Rebates So Give Us Total Control Over Medicare Drug Benefit

11/02/2016 12:54 PM | Robert Goldberg

A recent article in MedPage - Insurers to CMS, Congress: For Lower Rx Costs, Hand Us the Reins – needs a bit of translation to help people under stand what handing insurers the rein over what drugs and how much to spend really means.   For instance, the headline should actually read "Insurers to CMS, Congress: We Want More Rx Rebates So Give Us Total Control Over Medicare Drug Benefit" 

According to Medpage: “Congress and the administration can help rein in rising drug costs through a few key regulatory and legal fixes, said insurers and pharmacists at AHIP's National Conference on Medicare, Medicaid and Duals on Tuesday.”

"I think plans need to be given a little bit more leeway to truly assess the value of drugs to make a decision: does this drug at the cost really provide any additional value?" said Sarah Marche, PharmD, vice president of pharmacy services at Highmark, a Blue Cross affiliate in Pennsylvania.

Translation:  We already limit access to life saving medicines for the most chronically and seriously ill seniors based on our current value assessment.   But we want even more control over what patients get.   And by ‘additional value’ we mean increasing the 35-40 percent price discounts we get and what consumers are charged.  We want more. 

Marche noted that not every drug Medicare covers adds value.
"Glumetza [a branded version of metformin] provides no value above and beyond what's available, and if you look at a lot of the commercial formularies, it's blocked," she said. "Nobody's dying. Nobody has any huge issues with that, but we don't have that same flexibility within the Medicare space. So, you're covering a drug that really provides no additional value, just increasing the cost."

Translation:  After Valeant got hammered for hiking Glumetza by more than 800% in 2015, the list price of  stood at $10,020 for 90 tablets, up from $896 in January 2013,.  For the longest time, insurers didn’t complain  .  Half of Glumetza’s price is  given back in discounts, rebates, chargebacks, and the like to wholesalers, managed care organizations, pharmacy benefit managers, federal and state healthcare programs, and others. 

 Under pressure to reduce prices, Valeant gave Walgreens’s an exclusive deal to sell Glumetza as generic prices.  So Express Scripts, the company running our drug benefit decided it could turned around an blocked Glumetza and cutting a deal with a company making a generic version of the drug to make up for the lost rebate revenue.  So we would have covered it if had provided additional profit… I mean value to us regardless of cost.  It really depends on the rebates Express Scripts can share with us.  

Another panelist, Mark Owen, MBA, president of government programs for the the Blue Cross-affiliated Health Care Service Corp., power “to limit beneficiary access to specialty pharmacies.” 

While Owen noted that critics of the idea have said such a change could pose access challenges, he argued that allowing plans to direct beneficiaries towards only certain pharmacies could lower costs and increase adherence.

Translation:   Limiting access allows us to pocket more money because it  ensures  patients have no choice but to take the drugs that we give them.  That way we make the biggest profit margin whether they like it or not.  And we know that charging patients about 40 percent of the retail price of products is a good way to force them to use drugs what give us the biggest margin.   We will work really hard to increase adherence, but only with drugs that fatten our bottom line regardless of whether the drug works for that patient or not.




 
  Read More & Comment...

Abusing the Privilege?

11/02/2016 07:37 AM | Peter Pitts

From Medpage Today ...

FDA, Industry Focus on Abuse-Deterrent Opioids

No consensus immediately apparent after 2-day meeting

FDA officials and representatives from both the generic and branded drug industries spent two days hashing out next steps for development of abuse-deterrent opioids.

The two topics on the table: reviewing a draft guidance for the development of generic versions of abuse-deterrent opioids, and developing standard in vitro testing methods to characterize a drug's abuse-deterrent properties.

The meeting was in line with FDA's strategic plan for mitigating the opioid epidemic, which it released in February 2016, said Douglas Throckmorton, MD, deputy director of regulatory programs at the FDA's Center for Drug Evaluation and Research. That includes incentivizing the development of "progressively better" abuse-deterrent opioids and supporting a transition to these products, he said.

Throckmorton acknowledged the tension between generic and branded developers, but advocated working together to come up with a solution that benefits all parties.

"If you all came up with a single approach that suits the best product development, we would be delighted and take it very seriously," Throckmorton said. "It would move the field a great deal. It would require careful collaboration, but it's been successful in other fields, like drug-eluting stents, which had a similar challenge but the industry pulled together and made suggestions we all make use of."

FDA released its draft guidance for evaluating generic abuse-deterrent formulations last March, with the goal of ensuring that a generic is no less abuse-deterrent than the brand-name opioid. No generic abuse-deterrent opioids are currently approved.

In general, an ANDA applicant isn't required to provide independent evidence of the safety and effectiveness of the generic drug; instead it relies on the FDA finding that the previously approved product is safe and effective and must demonstrate that the generic is "bioequivalent" to the reference drug, primarily on the basis of pharmacokinetic studies.

Robert Lionberger, PhD, director of the office of research and standards in the FDA CDER's office of generic drugs, noted that the ANDA for any generic abuse-deterrent opioid would cover all routes of abuse: oral, nasal, injected, and smoked. It would also evaluate the drug in comparative in vitro studies and, in some cases, in relevant pharmacokinetic or other studies to show it is no less abuse-deterrent.

But some industry voices -- particularly from the branded industry -- said these assessments did not go far enough.

"I am concerned that this draft guidance is not sufficient to ensure that generic versions will be no less abusable than the reference drugs," said Alexander Kraus, PhD, of Grunenthal USA in Morristown, N.J. "It does not do enough to ensure that the generic meets therapeutic equivalence. It can't be based solely on in vitro testing. I encourage the FDA to require not only Category I in vitro tests, but Category II pharmacokinetic and Category III human reference studies as well."

Those Category I in vitro tests for abuse-deterrent opioids have their own issues to be worked out, which was why they were also a focus of the meeting.

Xiaoming Xu, PhD, a senior staff fellow at the FDA's division of product quality, said in vitro testing for abuse-deterrent opioids has not been standardized, making both comparisons with other drugs and overall assessments challenging.

Ideally, that testing should assess each potential route of abuse -- oral, injectable, nasal, and smoking -- starting with simple and gentle mechanical and chemical manipulations, progressing to complex and more destructive manipulations. It should also address mechanisms by which abusers can be expected to attempt to overcome abuse-deterrent properties as well as the ways that patients may alter the formulation to change the amount of of drug that gets released, Xu said.

The challenge is that the design of these experiments is complex: any single product can have more than a dozen possible methods to achieve a desired manipulation; scores of different solvents; different reactions to various temperature conditions; different volumes released, and so on. Indeed, the number of experiments can run into the thousands, Xu added.

The problem garnered unique observations about the automobile industry and coffee grinders. Richard Lostritto, PhD, acting associate director in the office of policy for pharmaceutical quality at FDA's CDER, noted that the auto industry standardized the type of hammer it would use in safety tests; Karsten Lindhardt, PhD, of Egalet Corporation, noted that he's had to buy several different types of coffee grinders to do proper in vitro testing.
"You end up with each material behaving differently," he said. "One grinder may be optimal for one drug but not for another."

Throckmorton acknowledged the tension between developing standardized versus individual tests for these types of analyses: "We've seen that even small changes in some formulations can have a large effect on product performance."

Although it was not a point of the meeting, critics at past FDA advisory committee meetings for abuse-deterrent opioids have called for epidemiologic data on whether or not these formulations can actually reduce abuse and the more serious consequences of addiction, overdose, and death.

Also, the meeting did not address patent issues, which generally fall outside FDA's jurisdiction. Although the major opioid drug compounds are now off-patent, it may be many years before patents expire on the specific abuse-deterrence technologies now in use.  Read More & Comment...

Lancet Oncology takes on Pharmacovigilance

11/01/2016 11:24 AM | Peter Pitts

The November issue of Lancet Oncology focuses on pharmacovigilance and drug safety. The lead editorial drives home some key points:

At a time when the number of biological agents due to come off patent is increasing, and in the face of a market fuelled by escalating drug prices and pressure from pharmaceutical companies and patient groups alike for expedited drug approval, issues surrounding the safety and efficacy of agents such as biosimilars and generics are paramount.

Substantial variation exists between high-income and low-to-middle-income countries with regards to manufacturing and supply chain regulation of generic drugs, despite countries such as India providing a large market share of generic drugs worldwide. Moreover, bioequivalence—a key consideration when comparing generic formulations with their trademarked counterparts—can vary substantially, making appropriate regulation particularly important. Issues of safety and regulation are further compounded when approving biosimilars: despite nearly 10 years’ of experience in dealing with biosimilar agents, regulators still need to streamline and expedite approval processes, and improve ways of reducing cost. Thus, taken together, the importance of pharmacovigilance has never been greater.

Given that multiple health-care systems encourage or enforce generic and biosimilar prescribing, sometimes without physician knowledge or consent, coupled with further potential complications created by generic or biosimilar switching during a course of treatment, pharmacovigilance needs to evolve beyond merely the uncovering, monitoring, and reporting of adverse events, to continual pre-marketing and post-marketing surveillance.
Although a focus on regulatory and policy issues is key to monitoring safety and     efficacy, especially for newer agents, there are other ways in which drug safety can be improved.

The November issue also includes my new paper, 21st century pharmacovigilance: efforts, roles, and responsibilities.

Here’s the abstract:

In an era when the number of expedited and conditional review pathways for newly available brand-name drugs and biosimilar medicines to treat serious and life-threatening diseases is increasing, defining pharmacovigilance has never been more crucial. 21st century pharmacovigilance is not merely about uncovering, reporting, and addressing adverse events associated with already approved and marketed agents, but can be described as the systematic monitoring of the process of pre-market review and post-market surveillance, which includes the use of medicines in everyday practice. Pharmacovigilance identifies previously unrecognised adverse events or changes in the patterns of these effects, the quality and adequacy of drug supply, and should ensure effective communication with the public, health-care professionals, and patients about the optimum safety and effective use of medicines. In this paper, the first in a Series of three about drug safety in oncology, we discuss evolving challenges in the purview, roles, and responsibilities of the US Food and Drug Administration and the European Medicines Agency with respect to pharmacovigilance efforts, with a special emphasis on oncology treatment.

If you’d like a copy of this article, please contact me at ppitts@cmpi.org.  Read More & Comment...

ICER Counts Lung Cancer Patients as 2/3 of a Healthy Person

10/26/2016 01:01 PM | Robert Goldberg

ICER released a report claiming that at retail prices,  immunotherapies (Tecentrig, Keytruda and Opdivo)  for non small cell lung cancer (after a first line of treatment) are not worth using compared to a 20 year old drug (docetaxel) that is 3-4 times less likely to help patients and when it does work, is half as effective in extending life and generating a treatment response.   The table below shows the significant clinical benefits of new drugs that block PDL-1 and PD-1 protein expression, 
 

Drug	Ratio of Patients Likely to    Benefit from Immunotherapy Compared to Docetaxel	Expected Survival in Months	Differnce in Duration of Response in Months
Docetaxel		8.5
Acentriq	3.4	14.8	7.2
Opdivo	4.0	11.1	11.6
Keytruda	3.8	19.4	Not reached

  Source: Institute for Clinical and Economic Review, Evidence Report - Non-Small Cell Lung        Cancer, Table 6 page 36 and Table 10 page 45

ICER determined that the maximum amount of money to be spent on an additional year of life in perfect health -- a quality adjusted life year (QALY) is $150K.   Which means that most of the new drugs developed and to extend the life of lung cancer patients over the past ten years would not be used. 

Applying the ICER QALY calculations to lung cancer patients over the past ten years, I found that if ICER had its way 10 years ago, and denied access to new lung cancer drugs, today the death rate from lung cancer would be 23 percent higher.  And the cost of care will be more expensive, increasing hospital related costs by $3 billion a year.

ICER ignores indirect costs, such as lost productivity and caregiver salaries or the productive possibilities of being able to make plans to marry, raise kids, compose music, travel, go to school. ICER ignores the value of two additional years of life to a patient who has run out of options.

But the worst element of the ICER framework is how it devalues the additional months and years of life people with advanced lung cancer can get from newer medicines.  

At face value ICER’s QALY standard of value is arbitrary. Patients who live twice as long as those taking a generic drug should be credited with the total years of extended life.  ICER believes that an additional year of life for a lung cancer patient is really worth two-thirds of an additional year of life for a healthy person.  

        


Where has this metric been used before?    Article 1, Section 2, Paragraph 3 of the United States Constitution, which allowed slave states and their collective slave drivers to count each of their slaves as 3/5 of a white man.  

To mind the use of a QALY in determining access and drug prices violates the spirit, if not the letter of the Equal Protection Clause.

Worse (perhaps)ICER uses that same discriminatory rationale by assigning a lower value to patients and a higher value to insurers.   When it comes to patients, ICER uses the retail price of the drug to determine a QALY   When it comes to payors,  ICER uses the price or cost of the drug LESS any cost savings generated. 
 

Immunotherapy	Payer Cost per patient  net of drug generated savings	Cost used for patient QALY
Tencentriq	39000	102519
Keytruda	73900	108841
Opdivo	44500	180489

ICER is the worst example of how economic analysis has been applied to health care.  In the end, it is not about numbers. It is about people and the additional years and vitality medical innovation generates.  ICER is not alone in failing to factor in the economic value of hope or the virtue of forward looking, of having a project.

Modern medicines are extending lives, improving lives and saving lives. Setting an arbitrary limit on what that is worth is simply closing the door on medical progress, increasing the death rate and driving up costs at the same time.  And it also forecloses the possibilities of life that, while intangible or uncounted, adds more to our well-being than consumption.  As the great economist Irving Fisher noted: The true “wealth of nations” is the health of its individuals. And greater health through the diffusion of medical innovation is the most important way to eliminate inequality and eliminate barriers to people battling disease. ICER's value framework diminishes the value of longer life as part of an effort to show most new drugs are NOT cost effective.   In doing so, it is violating the civil rights of people because they have lung cancer.   



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Bernie's Terrible Tweet

10/23/2016 08:34 PM | Peter Pitts

In a recent tweet, Senator Bernie Sanders made it clear he’s upset about high drug prices. Less clear is that his righteous wrath will put patients in harm’s way.  He proved yet again he’s uninformed about the facts and unconcerned about the unintended consequences of his actions.

The target of Senator Sanders terrible tweet was a small innovative pharmaceutical company (Ariad Pharmaceuticals) and its innovative drug Iclusig (for chronic myeloid leukemia treatment). The company raised the price – and Senator Sanders can’t see why. He should open his eyes.

A few facts that are worth sharing. The first is that Iclusig serves a population of approximately 1,000 to 2,000 patients. And these patients have limited options. Ariad Pharmaceuticals, works to ensures that no patient is prevented from treatment due to price. (They provide a robust support program for patients who have accessibility and affordability concerns.)

Second, these types of ultra-orphan disease cancer patient population programs require large investments and face tremendous odds.  Ariad sure doesn’t look profitable. They’ve invested more than $1.3 billion in R&D and accumulated losses of approximately $1.4 billion since the company was founded. But they’re betting on innovation. In 2015, Ariad generated $119 million in total revenue and invested $171 million, or 143% of revenue, in R&D alone.

Third and most importantly, Iclusig works.  It significantly increases 10-year survival rates for patients with no other hope or option except for expensive stem cell transplants and draconian radiation treatments.

Attention Senator Sanders. It’s not just a question of an ecosystem-driven price. It’s also about investment and value – precisely the rationale behind the Orphan Drug Act -- to encourage investment in treatments for small and in this case, tiny, populations. “Facts,” as John Adams quipped, “are pesky things.
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Fact Checking Hillary on Drug Pricing

10/23/2016 08:30 PM | Peter Pitts

As seen in the Daily Caller

Fact Checking Hillary Clinton On Drug Pricing

Both Donald Trump and Hillary Clinton get a lot of flak for lying. But in Secretary Clinton’s latest speech on healthcare reform, she didn’t lie — she just got all her facts wrong.

Clinton used her speech to demonize pharmaceutical companies. She argued that greedy firms are gouging consumers and that government-imposed price controls are needed to protect us from them. Her rhetoric ignores reality and her proposals would harm the patients she wants to help.

According to Mrs. Clinton, Americans are “paying the highest price” for medicines, compared to citizens of other developed nations.  She implied that drugcompanies are overcharging Americans just because they can. It’s not so simple.

The real reason medicines are more expensive in the United States is that the socialized medicine systems in other countries cap prices on innovator drugs, while also rationing their use. Many foreign governments threaten to break ‘drug patents if firms don’t agree to sell their products at below-market rates. As a result, American consumers shoulder a disproportionate share of the world’s research and development burden. That’s “free-riderism” and it’s not fair. It’s also important to note that generic drugs, which account for 85 percent by volume of all the medicines used in the United States, are cheaper here than in Europe or Canada.

 But the answer isn’t to impose our own price caps. That would only discourage research into new medicines. Here’s a fact that Clinton didn’t mention — America invents more than half of new medicines in the world.  Stifling U.S. research would lead to vastly fewer medicines here and across the globe. It’d be smarter economically, and better for patients, to negotiate stronger trade protections to prevent other nations from freeloading off American investments.

Secretary Clinton told her audience that their tax dollars fund drug safety evaluations. They do not. All of the complex and costly clinical trials that must be done to bring a new medicine to market are fielded and funded — 100 percent — by the pharmaceutical industry. They are then reviewed by the Food and Drug Administration. And industry pays for that privilege through “user fees” the FDA collects from pharmaceutical companies.

She also slammed the Medicare Part D drug benefit, touting a doctor’s claim that he “can’t prescribe certain drugs that [his] patients need” because government health programs won’t pay for them. But when it comes to Medicare, that assertion is simply false. Medicare’s prescription drug plans cover, on average, 191 of the 200 medicines most used by seniors.  That’s more than most Obamacare exchange options.

In her assault on capitalism and private enterprise, Secretary Clinton singled out the price of hepatitis C drugs. She claimed that makers of these cures — which are vastly more effective than previous therapies — are gouging Americans.

The truth is radically different – and highly documented. Hepatitis C drugs are now cheaper in the United States than in Western Europe, thanks to a price war between competing manufacturers.  Clinton inadvertently picked an example that proves the free market yields better, cheaper medicines than socialist systems and fix prices and ration care.

Bashing the companies that research and produce the world’s most groundbreaking medicines might give Clinton a bump in the polls. But her reality-free rhetoric has dangerous consequences.

Clinton’s attacks on drug makers have prompted a sell-off of biotech stocks multiple times over the past year.  If companies can’t raise funding from investors, they’ll have to limit new research projects. That means fewer drugs down the road. What’s political expediency worth?

And if Clinton reaches the White House and actually implements price controls, it’s statistically certain Americans will lose out on lifesaving drugs. Price controls in other countries depress research spending by up to $8 billion each year — the equivalent of three or four new drugs, according to a Department of Commerce study.

For a super policy wonk, Secretary Clinton got an awful lot wrong in her recent speech. If she really wants to help patients, perhaps she should pay a little less attention to her focus groups and a little more attention to the facts.

Peter J. Pitts, a former FDA Associate Commissioner, is president of the Center for Medicine in the Public Interest. 
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Clinton Campaign Considered Targeting FDA's Califf

10/21/2016 02:45 PM | Robert Goldberg

The Wikileaks disclosure of John Podesta's emails reveals that the Clinton campaign considered attacking FDA Commissioner Robert Califf for ties to drug companies as part of a broader effort to divert attention from Secretary Clinton's email scandal.


FDA Commissioner and Clinton Campaign Target Robert Califf, MD


It start with an email from long-time Clinton adviser Mandy Grunwald to Clinton policy adviser Ann O Leary.  The email contains a link to a NY Times article on acting FDA Commissioner Rob Califf who had been nominated by President Obama to become the full time commish.  

On Sep 21, 2015, at 10:33 PM, Mandy Grunwald sent an email to Clintion policy advierse Jake Sullivan and Ann O'Leary,  Joel Benenson a strategist and pollster for the presidential campaign., press secretary Brian Fallon and Communications Director Jennifer Palmieri and asks: Do we want to weigh in on this?

Jake Sullivan responds:   What do you think?

On Mon, Sep 21, 2015 Mandy Grunwald replies: I don't know anything about the guy. If we weren't hitting the Administration with Keystone this week, I might be tempted, but I think that probably makes it a bad idea. Lets keep an eye on it and see about those Pharma ties. 

Then Anne O Leary:  Interesting. I'll do some asking around to see what folks in the public health world think.

On Sat, Sep 26, 2015 at 12:53 PM, Brian Fallon :  Any update on this? As we consider fights that fit into the larger themes we are trying to promote, this seems like a good fight to have. Plus, the VP would be in a box of having to support this nominee.

On Sat, Sep 26, 2015 at 12:59 PM, Jake Sullivan wrote: This is ultimately a political call, not a policy call. I don't really like the idea of bashing this White House's nominees, knowing their vetting process and standards.  But if you guys want to do it, I cannot identify a policy reason not to -- you all know the facts. Ann, any other intel?

On September 26, 2015 at 1:13 pm  Anne O'Leary wrote:

Califf the Obama nominee does have real ties to the drug industry - Chris Jennings is calling a few people for me to learn more so we don't tip our hand directly. We are clean on Clinton Admin FDA Commissioner - it was David Kessler, an academic who had run a teaching hospital - and best known for taking on big tobacco. We could certainly signal that we want someone willing to stand up to Pharma (in the same way Kessler stood up to Tobacco). BUT - I want to do a little more digging and due diligence before we hit this guy. Having been through a nomination fight with my husband (in which he lost), this is personal and messy and horrible on the person nominated and their families - so I don't take attacking this guy lightly. Do you want to do it on Meet the Press? 

That was follwed by an email from Podesta on Sep 26, 2015, at 2:27 PM,  who wrote: " I think we will pay a huge price with the WH on this one. Worries me."

Nothing transpired.   But the back and forth about whether to trash Califf came down to politics, not policy differences.  And it had NOTHING to do with Califf as a person, a physician, a researcher and public servant.  It was clear that Team Clinton was interested only in dirt that was newsworthy.  It was simply a matter of whether attacking Califf on Meet The Press would be worth the headache of taking on an Obama nominee.   How lovely. 

Rob Califf should remain FDA commissioner regardless of who is elected president because of his qualifications and commitment to accelerating access to safe and effective medicines.   I am concerned that the Clinton team -- which exults about going to war against Pharma -- will seek to replace Dr. Califf.  That will trigger a prolonged political war that will undermine the FDA.    

The emails reveal a Team Clinton eager to find ways to smash up people for short term political gain without tipping their hand that they are behind the hit job.   Like it's war on pharma, it has less to do with policies and more to do about the benefits of creating and attacking enemies. 


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​Limiting co-pay assistance is against medicine’s tradition of benevolence

10/14/2016 04:43 PM | Robert Goldberg

Written by Rafael Fonseca MD and Robert Goldberg PhD

Two recent articles in the NEJM (1) e) and Annals of Internal Medicine (2) propose that restrictions or eliminations of co-pay assistance programs by pharmaceutical companies are needed since they distort the market and therefore, while few benefit, many suffer in the form of higher healthcare expenditures. They are factually correct but the conclusions point to a larger problem; the third party payer system in health care. When consumers (in this case patients) are detached from the price consequence of transactions they will be less careful in their selections. However, the proposal presented in these articles are, at least in the short-term, patient unfriendly and immediate implementation of their recommendations would limit, severely, access; particularly for patients with serious or life-threatening conditions. The Annals article is notorious in that it fails to mention the increased cost-sharing pressure that patients are facing from the payers.

So what are the solutions?  Ideally, healthcare should be divided between the routine care and the catastrophic care.  Routine care should involve much more “skin in the game.”  In my view, regular care should not be covered under traditional heath insurance but be bought directly, with compassionate support tools for those in need.  In this type of care I could envision more direct pressure in the selection of older medications for which many alternative exist. There are many options for anti-hypertensive medications, statins, etc.  In the absence of a third party payer system the Epipen would never cost $600.  This is where consumer pressure, with co-pay requirement as a discriminator, should be employed; vigorously, if you may.  I would not disagree that if an equivalent generic exists, a true equivalent, then having the patient paying more for a branded product is fine.  This is not to say that branded products and generics are always the same.  Sometimes production quality may suffer or sometimes an alternative may not be the same as the original, similar and yet not the same product.  But if you want the branded statin maybe you should pay a bit more.  Who could argue with that?

However, for more expensive medications, medications used for serious, chronic severe or catastrophic illnesses the pressure seems misguided.  For instance preventing co-pay assistance for patients with cancer seems inhumane.  Dusetzina and colleagues have documented that lack of supplemental insurance delays initiation of treatment for CML (3). Should we disincentivize the use of medications that can be lifesaving for a cancer patient so they consider inferior treatments?  Should we place additional burdens in someone who is at high risk for bankruptcy? Someone who cannot work or whose caregiver cannot work?  That seems inappropriate.  Furthermore, for many of these newer and expensive medications there are no suitable alternatives (4).  Dr. Bach and colleagues were able to reduce the price of a competing monoclonal antibody, but that is a rarity in oncology and more of an exception. Should myeloma patients forgo lenalidomide in favor or thalidomide and face certain peripheral neuropathy?  Or should a diabetic myeloma patient be forced to be treated with bortezomib instead of carfilzomib and again face neuropathy? To create a disincentive as this for people facing serious medical illness appears to me as a fundamental violation of medicine’s stance of benevolence. Rather this has the appeal of altruism, sacrifice the few for the benefit of the many.

Lastly, government regulations that eliminate this co-pay assistance are demonstrably patient unfriendly. Commercially insured patients can receive this directly and in another study by Dusetzina she shows that the average co-pay for specialty medications is only $35 (5). In another study it was shown that 90% of myeloma patients pay less than $100 per month for lenalidomide, a backbone for the treatment of this disease. In the meantime, Medicare beneficiaries struggle to find indirect support with funds provided by the pharmaceutical companies to third parties. I’ve written about this topic before, but again is a built-in disincentive to lessen the use of medications (6).  What if these medications save dollars by preventing hospitalizations and decreasing expenses elsewhere?  Once again it is pound foolish to only concentrate on the price of drugs.

References
1.    Dafny LS, Ody CJ, Schmitt MA. Undermining Value-Based Purchasing - Lessons from the Pharmaceutical Industry. The New England journal of medicine. 2016. Epub 2016/10/13. doi: 10.1056/NEJMp1607378. PubMed PMID: 27732125.
2.    Ubel PA, Bach PB. Copay Assistance for Expensive Drugs: A Helping Hand That Raises Costs. Annals of internal medicine. 2016. Epub 2016/10/11. doi: 10.7326/M16-1334. PubMed PMID: 27723893.
3.    Winn A, Keating N, Dusetzina S. Factors Associated With Tyrosine Kinase Inhibitor Initiation and Adherence Among Medicare Beneficiaries With Chronic Myeloid Leukemia. Journal of Clinical Oncology. 2016;10.1200/JCO.2016.67.4184.
4.    Fonseca R. 2016. Available from: https://tmblr.co/Z0_1wo2CgPnw1.
5.    Dusetzina SB. Share Of Specialty Drugs In Commercial Plans Nearly Quadrupled, 2003-14. Health Aff (Millwood). 2016;35(7):1241-6. Epub 2016/07/08. doi: 10.1377/hlthaff.2015.1657. PubMed PMID: 27385240.
6.    Fonseca R. 2016. Available from: https://tmblr.co/Z0_1wo2D7lHbj.
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Insurers not covering new cancer treatments

10/13/2016 01:49 PM | Peter Pitts

From the pages of today's edition of the Boston Herald:

Insurers not covering new cancer treatments

Poor insurance coverage is causing cancer patients to miss out on cutting-edge technologies that use gene analysis to determine the best treatments — a fact a former commissioner of the Food and Drug Administration is calling another example of Obamacare’s failure to provide Americans with high-quality health care.

“There’s a degree of dishonesty about what the Affordable Care Act provides, and that is starkly clear when a patient has a serious type of cancer,” said former FDA Associate Commissioner Peter J. Pitts, who now serves as president of the Center for Medicine in the Public Interest. “The soundbite of the ACA is, many more Americans now have health insurance. But the health insurance isn’t worth the paper it’s written on.”

Pitts said companies are covering the old-fashioned, less-effective chemotherapy regimens rather than more sophisticated approaches and prescription benefit managers are opting not to reimburse the more innovative, expensive treatments. Instead, they are negotiating rebates with pharmaceutical companies that they pocket, rather than passing the savings along to the patient.

“It’s time for insurance companies and prescription benefit managers to step up and do the right thing by putting patients first,” Pitts said. “When they choose not to reimburse for a product because it doesn’t earn them enough money, even though it could save a patient’s life, I think it’s despicable.”

And coverage for the treatments tends to vary by tens of thousands of dollars nationwide, depending on the company and geographic region, according to a University of Texas MD Anderson Cancer Center study published Monday in the journal Cancer.

The study found that insurance costs varied by as much as $47,000 for women on a chemotherapy plan that included the drug Herceptin, which is used to treat breast and stomach cancers by keeping cell growth at bay — and out-of-pocket costs range from $2,700 to $3,400.

The extra costs caused by these variations leads to an additional $1 billion spent to treat breast cancer in the U.S. each year, the study found. But cancer patients will often be covered for a treatment if it has been proven effective by the FDA, according to Dr. Harold Burstein, a breast cancer specialist at Dana-Farber Cancer Institute, who said: “The business of cures not being covered is extraordinarily uncommon.”

Many of the additional costs for the patient, he said, come in the form of lost income and child care.

“Those things are harder to measure than direct hospital bills,” he said, “and they generally have more of an impact.”  Read More & Comment...

Anthem Health Covers Massages But Not New Drug For Muscular Dystrophy

10/11/2016 02:20 PM | Robert Goldberg

Anthem Health has issued a decision deny coverage of Exondys 51, the first drug to treat a form of Duchenne’s muscular dystrophy.  As STAT’s Ed Silverman reports : Anthem “claims that the drug is “not medically necessary” and that “the clinical benefit … has not been demonstrated.” Duchenne is a rare disease that confines boys to wheelchairs and condemns them to an early death.

The decision was followed by this: "Exondys 51 failed to show it improves health outcomes, and therefore it is not a covered benefit for our members," Anthem spokeswoman Leslie Porras said in an emailed statement on Friday.

Not exactly.   Anthem conveniently ignored the fact that the FDA does not approve drugs that have no medical benefit or more precisely,  the FDA approves drugs that are likely to promote treatment of specific conditions.  Anthem claims it is denying coverage because a multitude of limitations cast further doubt on the reliability of dystrophin levels as a surrogate endpoint for clinical efficacy in DMD (FDA, 2016).   But these limitations were considered and approval was given.  In fact, in ignoring the FDA’s decision Anthem is taking refuge in the statements of FDA reviewers who raised concerns about clinical trials but were overruled by Janet Woodcock and Robert Califf, the FDA commissioner.  

I wonder if Anthem would have a problem with doctors and its utilization review munchkins ignoring the company’s medical policy on any treatment based on evidence ultimately rejected by Anthem.   And I wonder what a disability rights attorney will do with the fact that Anthem is willfully misapplying the term medically necessary.  

In fact, Anthem has no problem covering acupuncture, massage therapy, spine manipulations and naturopathy.   

Compare Anthem’s demand for more evidence before covering Exondys with the statement accompanying it’s decision to cover acupuncture:

"Acupuncture as a therapeutic intervention is widely practiced in the United States. There have been many studies of its potential usefulness. However, many of these studies provide equivocal results because of design, sample size, and other factors. The issue is further complicated by inherent difficulties in the use of appropriate controls, such as placebo and sham acupuncture groups…Further research is likely to uncover additional areas where acupuncture interventions will be useful.”

Anthem covers treatments that have less medical evidence of benefit for less severe ailments than DMD.  And it covers treatments based on the it’s belief that research will find acupuncture useful” (though not clinically effective.)   That’s because they attract millions of fairly healthy consumers.

There are about 17000 boys with DMD.    Providing the drug also means paying for all the other supportive services, emergency care, hospitalizations that such kids may require.  To Anthem, spending money to help boys with DMD stay independent and alive is a money loser. 

That’s the only evidence Anthem cares about.    Read More & Comment...

Artificial Intelligence and 21st Century Pharmacovigilance

10/06/2016 08:01 AM | Peter Pitts

From today's edition of Morning Consult ...

21st Century Pharmacovigilance and the Role of Artificial Intelligence

Artificial intelligence has an unimaginable potential. Within the next couple of years, it will revolutionize every area of our life, including medicine — and pharmacovigilance. Usually, we make sense of the world around us with the help of rules and processes that build up a system. The world of Big Data is so huge that we will need artificial intelligence to be able to keep track of it.

With the evolution of digital capacity, more and more data is produced and stored in the digital space. The amount of available digital data is growing by a mind-blowing speed, doubling every two years. In 2013, it encompassed 4.4 zettabytes, however by 2020 the digital universe — the data we create and copy annually — will reach 44 zettabytes, or 44 trillion gigabytes.

In a world increasingly driven by outcomes reporting and Big Data, more patient-level information from individual consumers is not always synonymous with better information. The good news is that artificial intelligence will facilitate what the pharmacovigilance ecosystem lacks today — a coordinated and efficient systems for developing actionable evidence on safety and effectiveness.

Today, the absence of these capabilities significantly affects the public health by creating obstacles for patients and clinicians to receive the meaningful information they need to make informed decisions, perpetuating unnecessarily long delays and gaps in effective and timely safety communications and recall management, hindering the timely development of new and innovative treatment options, and increasing the overall costs and inefficiency of the healthcare system.

In considering the role artificial intelligence can play in the both the near and long-term future of outcomes centricity, we need to discuss the concept of Design Thinking which requires cross-examination of the filters used in defining a problem and to revise the potential opportunities before developing strategies and tactics. Design Thinking requires cross-functional insights into a problem by varied perspectives as well as constant and relentless questioning. In Design Thinking observation takes center stage. In the “Sciences of the Artificial,” Herbert Simon has defined “design” as the “transformation of existing conditions into preferred ones.”

Unlike Critical Thinking, which is a process of analysis, Design Thinking is a creative process based on the creation of action-oriented ideas. AI can be a revolutionary tool to develop those action-oriented ideas. And, just for the record, “action-oriented” and “pharmacovigilance” are not mutually exclusive terms.

There is so much data to utilize: patient medical history records, treatment data — and lately information coming from wearable health trackers and sensors. This huge amount of data must be analyzed not only to provide patients who want to be proactive with better suggestions about lifestyle, but also to serve providers with instructive pieces of information about how to design healthcare based on the needs and habits of patients, and provide regulators not just with more data, but better date in context. Can AI usage for adverse event reporting and prediction be far behind?

Artificial intelligence is already found in several areas in health care, from data mining electronic health records to helping design treatment plans, from health assistance to medication management.

Artificial intelligence will have a huge impact on genetics and genomics, helping to identify patterns in huge data sets of genetic information and medical records, looking for mutations and linkages to disease. There are companies out there today inventing a new generation of computational technologies that can tell doctors what will happen within a cell when DNA is altered by genetic variation, whether natural or therapeutic. Imagine the predictive capabilities for pharmacovigilance.

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

If we are to reverse these tendencies and foster a new approach to creating evidence, we must bear in mind that there must be a common approach to how data is presented, reported and analyzed and strict methods for ensuring patient privacy and data security.

Rules of engagement must be transparent and developed through a process that builds consensus across the relevant ecosystem and its stakeholders. To ensure support across a diverse ecosystem that often includes competing priorities and incentives, the system’s output must be intended for the public good and be readily accessible to all stakeholders.

For any of this to work — and especially in the world of pharmacovigilace, we must view artificial intelligence through the lens of 21st century interoperability: the idea that different systems used by different groups of people can be used for a common purpose because those systems share standards and approaches.

And as Philip K. Dick wrote, “Reality is that which, when you stop believing in it, doesn’t go away.”

Will our socio-economic “technology gap” lead to a more pronounced “adherence/compliance gap?” It’s an important question. That’s why it’s crucial we remember there is no one-size-fits all solution. But that mustn’t mean we disregard the reality of the growth and pervasiveness of apps, mobile apps. Let’s face it, when it comes to mobile phones, any gap is rather narrow.

As the American industrialist Walter O’Malley once opined, “The future is just one damned thing after another.” Much depends not just on infrastructure, but also on capabilities, and trust.

The end goal is the same for all stakeholders — ensuring optimal use of resources for health care systems; improving access to value-adding medicines for patients; and appropriate reward for innovation.

As management guru W. Edwards Deming once quipped, “Change is not required. Survival is not necessary.”

Artificial Intelligence is here. Fasten your seat belts.  Read More & Comment...

Abuse Deterrent Opioids? Trick or Treat!

10/05/2016 09:47 AM | Peter Pitts

The FDA has announcing a public meeting to discuss scientific and technical issues relating to formulation development and pre-market evaluation of opioid drug products with abuse-deterrent properties. The meeting is intended to give FDA the opportunity to discuss, and seek public input from stakeholders on, the approach to testing FDA recommended in its draft guidance “General Principles for Evaluating the Abuse Deterrence of Generic Solid Oral Opioid Drug Products.” The meeting will also provide an opportunity to discuss FDA’s efforts to develop standardized in vitro testing methodologies for evaluating the abuse deterrence of opioid drug products. FDA is seeking input from all stakeholders, including patients, health care providers, health care payers, the pharmaceutical industry, patient advocates, academics, researchers, and other government entities.

The FDA may hold one or more additional meetings in the future to discuss the risk-benefit paradigm for opioid drug products to ensure that FDA is appropriately considering the full public health impact of prescription opioid drug products and the post-market impact (“real world effects”) of abuse-deterrent opioid drug products.

The public meeting will be held on October 31, 2016, from 8:30 a.m. to 4:30 p.m. and November 1, 2016, from 8:30 a.m. to 4 p.m.

Full details can be found here.  Read More & Comment...

Amy's Army

09/30/2016 02:36 PM | Robert Goldberg

Amy Stein Harvey  
My cousin Amy Stein Harvey passed away after living with ovarian cancer for 7 years. She was diagnosed at Stage III C and was told she would likely die within 3 years.   Not only did she "beat the odds" in addition to holding down a job and raising kids, Amy become a powerful advocate for cancer research and for legislation requiring new oral cancer drugs to have the same cost sharing as injectible.   She lived in Michigan, still one of only 8 states that have refused to enact oral parity.  Three days before she died, her friends and supporters participated in a walk in support of oral parity and research.  Amy's Army, as they call themselves will continue her fight.

 Her last post on Facebook (see below) is beyond inspirational.  She teaches us that the source of our urge to live longer is the desire to love and deepen our capacity to love.   

Amy, we will complete the mission you started.  We miss you and will always love you.  Give my mom a kiss for me... 


"Today marks another milestone for me. Today is my 7 year cancerversary! I have been fighting this awful disease for 7 long years. Some days are better than others, but I know that the next day things will turn around. They say that women diagnosed with stage IIIC ovarian cancer don't have a good survival rate. Well, take that stupid cancer. I have beaten the odds!! This past year has had more downs than ups, but I am hopefully on the right track now. I have gone to Washington DC and Lansing to let my voice be heard and put a face to a stastic, I have taken a fabulous cruise to Alaska, and I was able to see Benjamin finish elementary school. Cancer, you listen to me... you're never going to get me down! I am a fighter from the word go and I am going to win this war!!! So, I want to thank everyone for all they have done for our family and most importantly standing next to me in the fight of my life!!!"  Read More & Comment...

BMJ slings mud at FDA -- for shame!

09/28/2016 08:56 PM | Peter Pitts

A new report in the British Medical Journal “reveals” that many U.S. government regulators who review the safety of prescription drugs later go on to work for the pharmaceutical industry.

As opposed to – the automotive industry?

The authors identified individuals working at the FDA who were charged with reviewing hematology-oncology drugs from 2001 to 2010. They identified 55 reviewers. They found that 49 per cent were still employed with the FDA. Of the half that left, 58 per cent had moved on to jobs in the biopharmaceutical industry or as consultants to the industry. They could not find employment information for about 31 per cent of the reviewers who no longer work for the FDA. According to authors Jeffrey Bien and Vinay Prasad, “The transition from regulator to advising companies seems logical, but it raises concern as to whether regulators indefatigably act in the public interest.”

Hogwash.

Here’s what the FDA has to say:

"Federal laws and FDA ethics rules cover issues like outside employment, avoiding real and apparent conflicts of interest, recusals, disclosure requirements, protecting confidentiality, a ban on gifts from regulated industry, and avoiding conflicts should a federal employee choose to seek or negotiate outside employment," the spokesperson said. "Furthermore, past federal employees are bound by additional rules protecting the confidentiality of information they worked on while in federal service, a cooling-off requirement for senior employees, and other important rules against switching sides, contacting former employees, and contacting agency leaders."

And as the Pink Sheet reports:

“Peter Pitts, President of the Center for Medicine in the Public Interest and a former FDA associate commissioner, also slammed the findings of the report. He echoed FDA's comments, while also describing its authors as "ignorant."

"Former FDA employees understand the difference between sharing their expertise with industry and trying to unfairly influence their former colleagues," Pitts told the Pink Sheet. "They are the first to point out their jobs aren't to influence the agency but rather to share how best to properly communicate relevant information, and completely within appropriate limits. Former FDA employees understand the difference between sharing their expertise with industry and trying to unfairly influence their former colleagues. They are the first to point out their jobs aren't to influence the agency but rather to share how best to properly communicate relevant information, and completely within appropriate limits." Pitts added that he has never met a former FDAer "who ever asked for a short cut or an inappropriate edge. Shame on those who would allude otherwise." He further said that people should be applauding the fact that industry, like FDA, is looking to attract "the best and the brightest" to spur innovation.

Any former FDAer who tried to inappropriately influence an agency decision on behalf of a client would become persona non grata – and rightly so. What the authors seem not to understand is that there’s a world of difference between expert navigation and conflicts of interest.  Read More & Comment...

Will Mylan CEO School Congress On Rigged Drug Pricing System?

09/21/2016 08:43 AM | Robert Goldberg

Today Mylan CEO Heather Bresch testifies before a Congressional committee about EpiPen costs.   

I hope she is brutally honest and acknowledges that drug pricing is rigged by health plans, government programs and – above all – PBMs to extort as much money from drug companies and consumers as possible.  

She should explain how and why the price people pay at the drug store has little to do with drug companies raising prices and more about how much insurers and the companies that administer the drug benefit – pharmacy benefit management companies (PBMs) such as Express Scripts and CVS  -- want to charge and how much money they can make off of consumers. 

 The price charged to consumers is set by payors.  And that price is set to increase the spread between net drug prices and retail prices as the chart below shows.



More precisely, the behavior of PBMs – often portrayed as a consumer friendly efforts to keep drugs affordable – fits the classic definition of a cartel and price fixing.

A cartel is an organization of sellers or buyers that agree to fix selling prices, purchase prices, or reduce production using a variety of tactics.  The legal constructs of a cartel vary.  However, the acid test of any cartel is whether all consumers are harmed or helped by the practices. 

The PBM approach to pricing is more akin to a cartel than to a buying group that reduces the cost of the product or the production of the good in question. 

Epipen is a great example. 

Step One:  Create a monopoly or limit competition

Last November Sanofi ($SNY) pulled the main competitor for EpiPen--Auvi-Q--from the market, a turn of events that at time looked as if it “should keep Mylan dominating the epinephrine injection field.”
 
Mylan already had 85 percent market share.  

Then CVS and Express Scripts removed another competitor, Andrenaclick, from it’s formularies.   Andrenclick retails at $141 while EpiPen retails at around $600. 
 
Most people pay about $50 per Epipen pack.  But increasingly other plans have decided to make consumers pay thousands of dollars out of pocket before covering them.  Still others require consumers to pay up to half of the retail price of cost the product (About $600).  Some pay less than $3 because they are on Medicaid. 

Step 2.   After eliminating competition, fix both the acquisition and retail price of the drug to maximize profit. 

The PBMs then demanded higher rebates for giving Mylan privilege of being only covering EpiPens.  They were current getting about $400 rebates per EpiPen pack. 

When Mylan balked, CVS and Express Scripts moved EpiPen from the lowest cost sharing tier to the highest cost sharing tier most likely to pressure Mylan and to capitalize on that fact that people need the product to lead normal lives. 

Step 3. Require patients to pay part of or all of the retail price in order and NOT not the rebated price of a drug to generate even more profit. 

Indeed, here’s something Ms. Bresch should make clear: Consumer cost sharing for every other health care good or service is based on the discounted price insurers negotiate.  Except for prescriptions drugs.  On the contrary, we pay a share not of the rebated price of a drug, but the retail price.    

Step 4.  Force companies to cover the huge out of pocket costs of consumers based on the retail price. 

On top of rebates Mylan, under pressure for the increase in out of pocket cost is increasing the amount of money going to patients directly to reduce out of pocket costs.  Which means that Mylan is now forced to fork over rebates and cover the out of pocket cost of the drug, which also goes to the PBMs and insurers. 


The Mylan episode is repeated millions of times every day.  PBMs exclude drugs to create monopolies or cartels in exchange for more rebates.  Indeed, 77 percent of the retail price increase in drugs goes to rebates. This means much of the price increase imposed on patients reflects the cost of rebates that PBMs and other claim make medicines ‘affordable’.  

The Mylan sticker shock was due in part to the ability of PBMs to create monopolies, fix prices to maximize profit.  Indeed, the price fixing takes place at both the wholesale and retail level. Such practices are designed to increase the amount of cash they can collect by drug companies that – after paying rebates – provide to consumers to reduce out of pocket costs. 

Rebates are part of a rigged system that provide cash for big insurers, PBMs and hospital systems while patients wind up paying more, not less.  Manipulation of the quantity, acquisition cost and fixing the sale and resale price of products are classic aspects of a cartel.  Or at the very least, the rigged system is a series of “vertical price-fixing agreements, whereby a seller and a buyer agree with respect to the price at which the buyer will resell, have long been illegal per se. As is true with horizontal agreements, it does not matter how reasonable the agreed-upon price may be or how many good and sound reasons there are for the agreement. Nor does it matter whether the fixed price is a maximum rather than a minimum (although the per se rule against fixing maximum resale prices has encountered substantial criticism recently). 

It’s time for a change.  It’s time to end the rigged system which, in addition to the rebate ripoff includes the profits hospitals pocket when marking up and re-selling drugs that companies sell at a discount to help the poor.     Read More & Comment...