BioPharm companies are Inviting Price Controls By Inaction

10/29/2015 05:07 PM |

The Kaiser Family Foundation ran another health care survey that asked if people wanted price controls on drugs.  As I wrote after the last KFF price control poll the results are not suprising and consistent with surveys on the subject taken over 50 years.  

Let's set aside the fact that people have also supported price controls on hospitals, gas, oil, cable TV rates, etc.  The polls this time around are being used as part of a broader campaign to impose price controls on a state level and to get the next president to "do something" through executive order.  

Where is a poll that asks people what they think PBM and insurer cost sharing strategies.  In particular, where is the poll taken  after massive negative coverage (similar to that dumped on drug companies) showing how "PBMs to create a preference for drugs and generics that yield the greatest rebates and
profits. What is more, this arrangement actually incentivizes PBMs to promote the drugs for which they receive the largest per-prescription rebate,
rather than the cheapest or best-value prescription."  Or that insurers will pocket rebates and then force consumers to pay up to 40 percent of the cost of the rebated drug.  Or that insurers will create step therapy programs that reinforce their profit margin.

Don't you think Phrma should conduct it's own poll about price controls?  Guess what?  It did.  But the media ignored it as biased.  And a one and done poll will never get traction if it isn't part of a broader conversation. 

The industry will never get the media to cover this.  So it's up to them to invest time and money in a real campaign.  It had no problem forking over $150 million to the campaign to pass Obamacare.  You'd think they'd find the ability and resources to do the same to put drug prices in proper perspective.

If the industry thinks playing nice with it's opponents will work, it will be inviting price controls.   I don't  know how many times I have heard from pharma that they can't attack PBMs and insurers because they are "our" customers.   Meanwhile their customers are deeply involved in pushing price controls and running tough negative media campaigns against them.

There's a point at which concililation and civility is taken too far.  Past that point, it becomes defeat by default.

The collection of companies that comprise the biotech and pharma industry has developed and commercialized more important products than any known to humankind.  It -- and the hundreds of thousands of scientists working for them -- deserve better than to be treated like predators.  



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Are We Still Thrilled? Express Scripts Seeking to Limit Access to Cancer Rx the Same Way It Did With Hep C

10/23/2015 04:56 PM |

Ben Levisohn from Barron's discusses an analyst's report regarding the FDA's warning about Viekira Pak, one of the newer Hep C drug's.  

"Yesterday the FDA warned that Hep C treatments with Viekira Pak can – in some cases – cause serious liver injury mostly in patients with underlying, advanced liver disease. We believe this disclosure will impact some physician prescribing and drive incremental share shift to Gilead’s Hep C drugs. At the beginning of the year, Express Scripts positioned Viekira Pak as the exclusive option on its National Preferred Formulary (NFP) for patients with genotype 1, and we view this announcement as an incremental negative for Express Scripts. While Express Scripts also has access to Gilead’s (GILD) drugs (e.g., Sovaldi and Harvoni), we estimate that Express Scripts generates higher rebate dollars and profitability from Viekira Pak."

Note:  the reason for forcing patients to fail first on Viekira Pak before being 'allowed' to pay for another drug is to maximize profits.  

Two questions:

First, how many other step therapy or fail first protocols -- structured to maximize rebates and profits --  are exposing patients to drugs that could injure or kill them?  CMPI will be looking into this issue.  In depth. 

Second, I wonder what the ASCOs and oncologists posing as economists will do since they have essentially rallied around 'value' frameworks that extend the Express Scripts Hep C approach to cancer patients.  A few months ago,  these 'experts' were more than happy not only to put the seal of approval on fail first but also help design them.  

As in Peter Bach tweeting Thrilled @ExpressScripts to operationalize my Indication specific pricing model for cancer drugs    As in "clinical trial data and input from experts like Dr. Peter Bach, director of the Center for Health Policy and Outcomes at Memorial Sloan Kettering Cancer Center, will shape Express Scripts' further strategy."

If you are going to be thrilled about the operationalization, you should be willing to accept responsbility for the harm done when adopted.  

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Don Wright: Outrunning Cancer

10/23/2015 04:29 PM |

The Marine Corps Marathon is being run this weekend in Washington, DC.   The whole idea of a marathon never made sense to me.. why run that far when we have cars to get you there faster?   

But that was before I met Don Wright.  Don is 74 and running in his 90th -- as in just 10 less than a 100 -- marathon.  

Oh, and Don has had multiple myeloma since 2004.  

I met Don about 40 marathons ago in 2012.   He had just finished running his 50th marathon in Hawaii, which was the 50th state in which Don has completed such a race. 

He was diagnosed with the disease 12 years ago when his doctor told him that he had about 4 years to live, max.  Back then, all he wanted to do was run one marathon. He was fortunate enough to be put on an experimental medicine (now approved) that knocked the disease into remission.   As he has said more than once (but never enough)" It's just a little.. pill that I take every night."  Earlier this year Don was worried that he wouldn't be well enough to run the Marine Corps event.  It wasn't cancer.  He had a pulled hamstring from overtraining!

I have had the deep privilege of spending time with Don.  He is a powerful voice for medical innovation, a loving and dedicated husband and father and a source of comfort and support for everyone reeling from the diagnosis of a deadly disease.  

The greater marathon runner Bill Rogers once said, "the marathon can humble you."   Don Wright has shown that it can inspire us as well. 



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Opioid Conflicts at the CDC Drawing Heat on the Hill

10/21/2015 09:10 PM |

The American Academy of Pain Management sent this letter to the chair and key members of the House Energy and Commerce Committee, regarding the flawed process used by CDC in developing its opioid prescribing guidelines. The letter was also sent this letter to the chair and ranking member of the Senate HELP Committee.

The letter details the most important methodological shortcomings in CDC’s process, and asks that the committees investigate to determine why a more robust and appropriate procedure was not followed. Finally, the Academy asks the committees to suggest to CDC that they scrap this guideline and start over, using a more inclusive process.

This issue is not going away.

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It's the Cost of R and D Stupid

10/21/2015 11:46 AM |

An excellent piece by Razelle Kurzrock and Hagop Kantarjian among others, that puts the price of drugs in proper perspective.  The faster we bring medicines to market using new tools that promote precision medicine, the less expensive it will be to develop these medicines.  And the less expensive it is, because of greater certainty of benefit, the more investment (and competition) there will be. 

See what happens when regulation doesn't get in the way of producing valuable technologies?

Let's hope that this important article can be the foundation for a broader effort to promote faster, less expensive access to new medicines. 

The Urgent Need for Clinical Research Reform to Permit Faster, Less Expensive Access to New Therapies for Lethal Diseases
October 19, 2015

Written by David J Stewart, Gerald Batist, Hagop M. Kantarjian, Joan Schiller, John-Peter Bradford, Razelle Kurzrock

Technical Abstract

High costs of complying with drug development regulations slow progress and contribute to high drug prices and, hence, mounting health care costs.  If it is exorbitantly expensive to bring new therapies to approval, fewer agents can be developed with available resources, impeding the emergence of urgently needed treatments and escalating prices by limiting competition.  Excessive regulation produces numerous speed bumps on the road to drug authorization.  Although an explosion of knowledge could fuel rapid advances, progress has been slowed worldwide by inefficient regulatory and clinical research systems that limit access to therapies that prolong life and relieve suffering.  We must replace current compliance-centered regulation (appropriate for nonlethal diseases like acne) with “progress-centered regulation” in lethal diseases, where the overarching objective must be rapid, inexpensive development of effective new therapies.  We need to (i) reduce expensive, time-consuming preclinical toxicology and pharmacology assessments, which add little value; (ii) revamp the clinical trial approval process to make it fast and efficient; (iii) permit immediate multiple-site trial activation when an eligible patient is identified (“just-in-time” activation); (iv) reduce the requirement for excessive, low-value documentation; (v) replace this excessive documentation with sensible postmarketing surveillance; (vi) develop pragmatic investigator accreditation; (vii) where it is to the benefit of the patient, permit investigators latitude in deviating from protocols, without requiring approved amendments; (viii) confirm the value of predictive biomarkers before requiring the high costs of IDE/CLIA compliance; and (ix) approve agents based on high phase I–II response rates in defined subpopulations, rather than mandating expensive, time-consuming phase III trials.  Clin Cancer Res; 21(20); 4561–8.
2015 AACR.  Read More & Comment...

Towards an Intramural Approach to Biomarkers

10/21/2015 09:19 AM |

Towards a More Intramural Approach to Biomarker Development

A recent article by Shashi Amur and FDA colleagues on the future of biomarker development (Biomarker Qualification: Toward a Multiple Stakeholder Framework for Biomarker Development, Regulatory Acceptance, and Utilization) provides a solid foundation for ongoing development and review process for biomarker qualification. FDA should be applauded for their progress in agency collaboration with the Critical Path Institute (in biomarker consortia development), the recent total kidney volume and plasma fibrinogen prognostic marker approvals, and sponsorship of interactive sessions such as the recent CERSI meeting at University of Maryland, as well as their EMA partnership to facilitate collaborative review of drug development tool qualification.

We would encourage additional measures to hasten biomarker development, including:

• Maximizing Expert Resources: FDA needs adequate resources to provide advice and oversee review and decision-making. One solution is to partner with an external entity (an Intramural Biomarker Consortium-IBC) to develop early advice and serve as an expert sounding board for nascent biomarker efforts.  The IBC could be a required or voluntary resource in the review process, especially for initial data package reviews. This approach would allow FDA staff to focus on their primary role of product review and regulatory oversight.

• Refined Evidentiary Considerations: The product development and research community should collaborate to support FDA in developing a framework for the proper level of evidentiary substantiation required for qualification and the criteria used to evaluate them – such that FDA can issue guidance -standards which do not exist today.  The IBC could be charged with overseeing relevant workshops and the drafting of initial guidance documents (consistent with FDA’s Good Guidance Practice recommendations and provided FDA is actively participating and has final approval).

• Qualification Plan: FDA should clarify the components of individual qualification plans and judge submitted data packages against them.  Decisions not to qualify a proposed biomarker for a particular context should be accompanied by an explanation of the evidentiary gaps between the agreed plan and the submitted qualification package. IBC could work with biomarker developers to build these plans and perform initial data package reviews.

• Enhance Learning:  Give FDA the authority to share information about biomarker qualification programs that are being advanced through collaborative efforts. Much can be learned by reviewing successes and failures across ongoing biomarker programs, and would inform the broader research community to enable refined evidentiary standards.

• Timeliness: FDA must clarify and communicate timelines for the qualification process in order to foster predictability and encourage participation.  Such resources could be provided via PDUFA VI.

FDA can further solidify its place squarely in the center of the innovation ecosystem by fostering collaborative alliances with all stakeholders, enhancing qualification planning, sharing developmental endeavors, and clarifying standards.

Peter J. Pitts
President, Center for Medicines in the Public Interest
Former FDA Associate Commissioner

Timothy R. Franson, M.D.
Chief Medical Officer – YourEncore
Immediate Past President- US Pharmacopeial Convention

  Read More & Comment...

Insurers Rack Up Profits Raising Consumer Drug Costs

10/20/2015 11:18 AM |

Health plans and pharmacy benefit management firms are hiking co-insurance rates for new medicines.  As Adam Fein points out in his Drug Channels blog,  they are daring biopharma companies to NOT provide copay assistance which can amount up to 25 percent of the total cost of a drug.  (Federal programs like Medicare Part D don't allow patients to get such support directly.)  

Moreover, rebates cost biopharma about $40 billion each year.  Nearly 90 percent of that $40 billion ($36 billion) is passed on to health plans by PBMs.   In 2014,  health insurers generated  $663 billion in revenue, which means drug rebates are about 5 percent of total revenues.  

I now see another layer to the strategy of make drug prices, which are effectively set by PBMs and insurers with higher coinsurance, the issue and blaming drug companies.  It's all about making money coming and going.   PBMs and insurers can extract deeper discounts from companies whose products they carry AND get the innovator firms to pay for the chunk that consumers have to cover:

Adam discussed an IMS study " Emergence and Impact of Pharmacy Deductibles: Implications for Patients in Commercial Health Plans"  As he notes: "The report’s overarching theme is unsurprising: Higher out-of-pocket costs reduce patients’ adherence to drug therapy and increase prescription abandonment rates.

The report’s major contribution, however, links the growth in pharmacy deductibles to manufacturers’ copayment offset programs, which cover a beneficiary’s out-of-pocket costs for a brand-name drug. High deductible plans are shifting costs from payers to consumers and—in many cases—back to manufacturers.

The findings echo what payers have been doing by adding coinsurance rates to higher-tier products, per Employers Get Tougher About Pharmacy Benefits and Specialty Drug Management. Most people can’t afford to pay hundreds or thousands of dollars every month. Payers are therefore essentially daring pharmaceutical manufacturers not to pick up the patient’s coinsurance with a copayment offset program. This is the same dynamic that links the growth in four-tier benefit plans with copay offset program. See How the Fourth Tier Coinsurance Boom Drives Copay Offset Programs.

I’m not sure how many manufacturers have analyzed the codependent relationship between benefit design and their consumer-directed programs. This report suggests that such analysis would be truly therapeutic."

To which I would add.. maybe the innovators should show consumers how their drugs are priced by insurers to force them to cover the difference and suggest how patient hostile such an approach is.   This co-dependency undermines the doctor patient relationship and moves medicine away from the kind of personalized treatment selection medical innovation is making possible.    Read More & Comment...

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!
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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.

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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.

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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.”

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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.  

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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

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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.

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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.”

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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.

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