Sovaldi and the Price/Value Debate

07/21/2014 07:38 AM |

From today's edition of the New York Post.

Why ‘pricey’ drugs save money — and lives

Expensive new drugs often get fingered as the culprit to rising US health-care costs. The truth is closer to the reverse.

First off, it’s hard to see how pharmaceuticals can be a major driver of costs when they’re just over 11 percent of the total US health-care budget.

But more important is that even extremely pricey drugs still save money if used right.

Consider Sovaldi, which has a 90 percent cure rate for Hepatitis C, a disease affecting over 3 million Americans. A three-month treatment cycle of the new drug costs upward of $84,000. On the market for just a few months, Sovaldi has already clocked in a record-shattering $2.3 billion in sales.

Some are calling foul, accusing the drug’s developer — Gilead Sciences Inc. — of exploitative pricing. “The company in this case is asking for a blank check,” says Karen Ignagni, president of America’s Health Insurance Plans. “It will blow up family budgets, state Medicaid budgets, employer costs and wreak havoc on the federal debt.”

That’s 100 percent wrong — the exact opposite of reality. New, better medications are actually the best and swiftest way for this country to cut down on our health-care expenses. By more effectively combating disease and improving patients’ lives, drugs reduce long-term medical costs and bolster the overall economy.

Consider one pre-Sovaldi “best practice” treatment for Hepatitis C, the drug Pegasys. This requires one injection a week for 48 weeks — and very few patients see the treatment through to completion, so much of that treatment, both physician time and drug cost, is wasted. Nor is it that much cheaper: At about $7,000/month, the full course of treatment is over $70,000 — barely less than cost of the three months needed for Sovaldi to work a cure.

And the price of not using Sovaldi is very high. One in three patients with the Hepatitis C virus eventually develops liver cirrhosis, and managing these patients is costly. A “routine” liver transplant (where the liver is from a cadaver) costs close to $300,000; a “living donor” transplant is even more expensive.

Thanks to Sovaldi, a pill that cures the disease when taken once a day over 12 weeks will eradicate the need, the risks and the costs of liver transplantation. Such radical innovation deserves to be both lauded and rewarded.

And Sovaldi’s costs will come down. The initial price of such breakthrough medications reflects the huge R&D costs required to bring the drug to market, not avarice.

As Food and Drug Administration official Dr. Janet Woodcock noted of the Sovaldi controversy: “We may have to put a big down payment down now to get something really good.”

It’s remarkable that some large insurers have the chutzpah to complain that curing 3 million Americans of hepatitis C will bankrupt health-care systems. Data recently published by the PwC Health Research Institute suggests the reverse. The study shows that the use of Sovaldi will actually drive down overall spending within a decade. According to the authors, “The challenge may lie in targeting the patient most in need of the more expensive course of therapy.”

In short, drugs aren’t the cause of rising health-care costs — they’re the solution. Demonizing new treatments distracts from the real problem in the US biopharmaceutical industry: top-down cost-centric policies that focus on the near-term, short-changing long-term patient outcomes, and so endanger “sustainable innovation” by denying fair reimbursement for high-risk investment in R&D. (Research and development costs big even if a drug never makes it to market — and most don’t.)

New treatments are a bargain. Disease is always much more costly.

Unfortunately, under ObamaCare health plans are sticking more people with a bigger share of drug costs — a strategy designed to discourage use by the people in greatest need and direct outrage away from insurers to drug companies.

Breakthrough drugs could generate huge new savings in the US economy — but only if federal regulators don’t smother them in the womb with expensive and unnecessary legal hurdles. Left unencumbered, domestic medical innovation will generate the new treatments to improve lives, stave off disease and cut down on long-term health-care costs.

If we don’t reward risk-taking on behalf of human health, both will shrink.

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

Patient, treat thyself. Maybe.

07/18/2014 06:52 AM |

Whether it’s allergy medications, treatments for erectile dysfunction or high cholesterol, the issue of Rx-to-OTC switching is complicated, important – and timely. The FDA’s September 2011 draft guidance provides a valuable resource for those thinking about proceeding with OTC switches based on self-selection studies. It's fair to say that support of Rx-to-OTC switches reflects FDA's interest in drilling down for greater insight into consumers' thought processes.

Can a patient self-diagnose and self-dose?  Do symptoms hide another, potentially more serious, underlying condition?  And what of safety concerns?  In considering an Rx-to-OTC switch, the FDA looks to see whether patients can use the product safely without the oversight of a physician or pharmacist. This includes ensuring that the right patients use the drug in the appropriate way ("safe use"). The agency is not evaluating the risk-benefit of the product, since that was done earlier when it was approved as a prescription drug.

The journal SelfCare has published "an essential blueprint for designing and implementing any Rx-to-OTC drug development program," says lead author Bill Soller, professor and executive director of the Center for Consumer Self Care at the University of California, San Francisco, School of Pharmacy.  Well, maybe not essential -- but certainly intriguing.

Soller and his colleagues list questions - "OTC Considerations" - based on switch principles FDA set in 1990 and 1998 and questions to post-2002 advisory committees that evaluated first-in-class switches.

The analysis recommends 11 primary questions about the Rx fundamentals of a drug, its "OTCness" and overall risk vs. benefit.

1- Has the Rx product been on the market for a sufficient time and extent to enable full characterization of the drug's safety profile?

2- Can the condition be adequately self-diagnosed or is there a need for physician diagnosis?

3- Is the minimally effective dose known?

4- Are there efficacy studies needed to support the intended OTC use of the switch candidate?

5- What are the patterns of diagnosing, prescribing and patient use in the Rx setting related to OTC intended use?

6- Are the studies supporting OTCness generalizable to the intended OTC target population?

7-Do consumers understand key communication objectives of the label, relating to directions for use, contraindications, in-use warnings and precautions?

8- Do consumers show they would be likely to be able to assess and take action on the treatment effect (e.g., take appropriate action if the drug is not working, serious side effects emerge, or self-monitoring is needed)?

9- Do consumers demonstrate successful self-selection and de-selection of the product under conditions (or simulated conditions) of actual use?

10- Does the pattern of actual use support that the label can be successfully used in practice?

11- Do the benefits of OTC availability outweigh the risks?

The authors say FDA "uses its discretion to select areas of concentration for advisory committee discussions on switch." Factors influencing the agency's questions for advisory committees include the novelty and uniqueness of a proposed OTC indication or Rx active ingredient; intrinsic and extrinsic toxicity of a switch candidate; and robustness of published and NDA-derived data and worldwide post-marketing surveillance evaluations.

But there are other important factors at play that, while not entirely within the scope of FDA’s regulatory authority, need to be considered within the context of the broader Rx-to-OTC switch conversation. These factors fall under the general headline of “the consumer healthcare continuum.”

Today’s healthcare consumer has access to much more information than ever before. (Some of it is even accurate.) More importantly, they seek choice and empowerment. At the same time healthcare providers are under multiple pressures to further decrease the amount of time spent with their patients. Moving certain products from Rx to OTC would certainly decrease (in a safe and appropriate manner) a provider's patient load, while at the same time obviating the need for a patient (otherwise known as a “consumer”) to spend both the time and money (office co-pay as well as time off from work) required for an office visit -- allowing physicians to focus their limited time on high-risk patients or those with more complex conditions.

And what about the evolving role of pharmacists and the important question (among others) of pharmacy scope of practice (blood tests, etc.). The removal of the Rx designation doesn’t require the removal of a learned intermediary.

There is also good research showing that patients on OTC medications demonstrate higher rates of utilization. A 2013 study indicates that offering OTC forms of a prescription medication increased utilization per drug class by 30 percent, potentially closing treatment gaps.  And, in contrast with many Rx treatments for chronic disease (such as high cholesterol), adherence rates are higher for OTC medications.

Patient, treat thyself. That’s one way of looking at it. Knowledge is power. But is a little knowledge a dangerous thing?

The consumer healthcare continuum continues.

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Biosimilar Saftey and the Real Patient Voice

07/17/2014 07:35 AM |

Desperate too-clever-by-half efforts to derail biosimilar pharmacovigilance are contrary to the public health and require rebuttal.

Some generics manufacturers, payers, and national chain drug stores have interwoven half-truths, out of context comments and just plain misinformation to build a fatuous argument dressed up as support for patient safety. But the actual patient and safety communities are firmly on the polar opposite side – in favor of safety, choice, and transparency.

The insurance-industry driven effort claims that distinguishable names for biologics “could lead to patient and prescriber confusion, increasing the possibility of medication errors.”  Unpacking that a bit, biologics are complex therapies that are made from living cells and prescribed for patients with difficult-to-target, debilitating and life-threatening health conditions such as cancer, diabetes, MS, lupus, Crohn’s disease and rheumatoid arthritis. There are no generics for them but it is expected that the closest thing –  biosimilars – will soon enter the US marketplace. What the insurers are essentially saying is that, a biosimilar that relates to a biologic should have exactly the same name as that biologic. 

In the case of biologics and biosimilars, even minute differences between products can cause individual patients to respond differently even though each product is considered safe and effective. Of greatest concern is immunogenicity, which carries a significant risk for all biologics. Because of the size and complexity of the biologic molecule, patients can experience unwanted immune reactions; these reactions can occur months after a patient begins taking the medicine and it is often difficult to know if it is due to the reaction to the medicine or simply the progression of the patient’s condition.

With all of these considerations, it stands to reason that the name of biologics and biosimilars should be similar, not the same. But rather than taking my word for it, consider these important viewpoints:

“Distinguishable names…will enable the gathering of sufficient data to ultimately allow providers to fully understand how all biologics – including biosimilars – are performing for minorities. This will lessen the inevitable confusion and assure optimum medical care in the use of biosimilars among minority populations.” – From a June 10th letter to FDA signed by 22 of the leading U.S. organizations focused on minority health, including the National Alliance for Hispanic Health, National Hispanic Medical Association and National Medical Association.

“…For millions of female patients, any potential increase or decrease in effectiveness of a biologic, along with side effects and adverse reactions, will only be discovered after the treatment is approved and under active use…As states across the country look to the FDA for guidance on issues surrounding biosimilarity, interchangeability, and therapeutic substitution, the agency’s views on sex and genomic-based differences will be crucial…Distinguishable names will enable the gathering of sufficient data to ultimately allow providers to fully understand how all biologics – including biosimilars – are performing for both men and women.” – From a May 20th letter to FDA spearheaded by the Society for Women’s Health Research and signed by 45 other leading U.S. organizations focused on women’s health.

“Distinguishable names for biologics support the medical community’s vital post-approval learning curve about which medicines are best for their rare disease patients. Health care providers need to know that a prescribed medicine was actually given to the patient and whether a substitution was made and to what alternative product. This can’t be achieved unless biologic products—especially ones with similar therapeutic purposes—cannot be distinguished, tracked and studied.” – From a June 3rd letter to FDA by the National Organization for Rare Disorders (NORD), the umbrella organization representing the interests of the many advocacy groups that serve 30 million patients impacted by nearly 7,000 rare diseases.

By my estimate, the patient-focused organizations that have come out in support of distinguishable naming cover just about every single American family. Fully addressing all of the inaccuracies and agenda-driven language in the insurance-industry driven letter requires an extensive point-by-point rebuttal [link to one], but the key take-away is this:  if you’re for patient safety, you can’t be against distinguishable naming.

As acknowledged by WHO and regulatory bodies of every developed nation, biologics are not chemical compounds (e.g., statins) — they’re infinitely more complicated. When it comes to biosimilars, we need to be extremely thoughtful about how we set policy and strike a balance that promotes health and safety, rather than forcing a binary response that is driven by profits rather than patients.   Read More & Comment...

What Pharma Can Learn From World Cup Soccer

07/15/2014 09:15 PM |

Pharma companies have to take a page from the World Cup champion German soccer team and stay on offense about innovation.. all the time.    As the Wall Street Journal notes:

“After years of timid, low-scoring play, that one word has become the theme of Brazil's World Cup. When the history of this tournament is written, the sport's cognoscenti will likely point to it as an event that changed the game. The finalists, Germany and Argentina, have survived the most offense-oriented tournament of the modern era, a series of games where playing defensively almost guaranteed an early exit.”

Pharma could learn a lot from the World Cup champion German club.   Stay on offense. 

Last night I attended a dinner hosted by Poppy McDonald the publisher of The National Journal to discuss what “value” means to various health care interests.   Attendees included Chris Jennings, who advised both the Clinton and Obama administrations on health care reform, John Rother, the former head of policy for AARP (and now CEO of the National Coalition on Health Care), Nancy Ennis-Davenport who is the CEO of National Patient Advocacy Foundation and Alex Wayne, who writes about health care for Bloomberg.  Julie Rovner led the discussion. 

It was a lively group and the discussions were spirited and friendly.  The conversation quickly turned to and focused on the price of Solvadi and whether it was reasonable or not. 

I was struck by how, for the most part, few at the table thought in terms of what Solvadi would replace, how much money it would save relative to the cost of treating people with liver disease, the horrible side effects of current treatments and how a 12 week cure could and would affect productivity, disability costs, etc., etc. 

And while there was a lot of moaning about drug prices, there was scant discussion about the price of liver transplants, bone marrow grafts, intensive care, etc. 

Innovator drug firms have usually done a lousy job thinking about or making the case for the value of their products.  But even when they are good at it, they are not consistently making the case.  Too often they are on defense, using lobbyists to fend off regulation with apologies and explanations about the price of drugs.

And by playing defense, pharma, more than ever, is in danger of being booed and reviled.  The audience expects both sides to mount an offense.  Thus, “A team that dared to play passively for even the briefest period of a match was guaranteed to hear derisive howls from the Brazilian crowds, no matter how hot and humid it was or how tactically intelligent slowing down the game might have proven.
"Every team has realized you need a balance, that you need to attack and defend," said Avram Grant, the former manager of the English club Chelsea. "If all you do is defend, you lose."

All pharma does is play defense. At it’s peril. That’s what the dinner discussion about Solvadi and the World Cup showed me.  Read More & Comment...

Pet Peeves

07/15/2014 08:57 AM |

Imagine waking up in the morning and finding your beloved pet on the floor convulsing, motionless or dead.

Now stop imagining, because this was the real-life nightmare for horse trainers in both Lexington, Kentucky and Ocala, Florida when they found their horses experiencing seizures and thrashing in their stalls. In total, more than a dozen horses died or were severely injured – in some cases, paralyzed.

The cause of these horrific scenes – illegally compounded medicines.

These horses were prescribed illegal drug concoctions that contained unsafe levels of pyrimethamine. By one account 25 times the amount it was supposed to contain. A deadly overdose for innocent animals.

There is legal and appropriate animal drug compounding.  All legally compounded product starts with an FDA-approved product.  The product may then be modified by a trained pharmacist on the order of a veterinarian to treat the medical needs of an individual or group of animals such as adding flavorings, or turning tablets into an oral liquid for easier administration.

But some animal drug compounding pharmacies go far beyond those parameters – with deadly results.  They mass produce and market drugs that attempt to mimic FDA-approved products, often using untested bulk active ingredients, imported from countries that may not enforce the strict controls on drug manufacturing that FDA requires for approved products. These copies carry a cheaper price tag than approved drugs, but none of the consumer protection.

Why does this black market exist? It’s both expensive and time-consuming to take a drug through the FDA approval process. For animal drugs, this can take up to 10 years and cost up to $100 million.  But it is a process that protects consumers and their animals – by ensuring that the approved drug is both safe and effective at the labeled dose.

FDA permits a limited amount of necessary compounding from bulk ingredients in order to make sure medical needs can be met when there is no approved drug.  But these compounding pharmacies have taken the proverbial inch and run for murderous miles.  Despite their attempts to muddy the waters with lawsuits and rhetoric, the law is clear: FDA and three federal appeals courts have ruled that compounding animal drugs from bulk substances is illegal. Period.

Illegally compounded animal drugs have caused harm to more than just horses. One university veterinary hospital has reported that dogs and cats are brought in for medical care because their medicines aren’t working, only to find they were being treated with illegally compounded drugs.  The literature is full of reports showing these compounded drugs contain far more or far less than the amount of advertised active ingredient.  This is not acceptable.

As a former FDA Associate Commissioner (and a current dog owner), I know the agency has rigorous enforcement authority.  Pharmacies that engage in illegal manufacturing cannot be allowed to ignore the law and put animal health at risk in the name of selling a cheaper product. 

For several approved animal drugs, FDA has sent warning letters to these pharmacies, but often they were simply ignored and the illegal practices continued.  Unfortunately there has been little to no follow up by the agency. The FDA must do more and commit to strong and sustained enforcement to protect animal health.

What can you do? It’s frightening to think a drug given to your pet might not carry the guarantee of safety and effectiveness that comes with FDA approval.  The first step is to talk to your veterinarian about best treatment options for your pet.  Ask if the drug being prescribed is FDA-approved.  If there’s no approved drug and compounding is necessary, make sure the pharmacist preparing the compound has the credentials and license to do it safely and legally. Why that might sound obvious it is the only – and best – way to ensure the prescribed drug is what is best for your pet. If you have concerns about a pharmacy, check with your state Board of Pharmacy.  At the same time, FDA must do its job of protecting our pets and animals by more regularly and aggressively enforcing the law and regulations.    

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The Dangers of Mixing Libertarianism and Access to Experimental Medicines

07/14/2014 07:12 AM |

Per pending state legislation and a patient's riights to experimental medicines -- pure libertarianism isn't in the best interests of the public health.

Here is my commentary in the most recent edition of BioCentury.

Net/Net -- let's not do the wrong thing by trying to do the right thing.  Read More & Comment...

Cracking the Social Media Code

07/11/2014 07:51 AM |

From the pages of the Burrill Report …

Cracking the Social Media Code

The Burrill Report

The U.S. Food and Drug Administration recently issued two long-awaited draft guidances for drug and device makers' use of social media. The first concerns risk and benefit information, and the second addresses correcting misinformation published by others on the web. We spoke to Peter Pitts, president of the Center for Medicine in the Public Interest, about the issues of concern to the agency, why the industry has been slow to embrace social media, and how these new ways to communicate with patients are accelerating broader changes in the healthcare landscape.

  Read More & Comment...

AHIP Is A Four Letter Word For Lying

07/10/2014 01:11 PM |

The incessant mistatement of facts about the value of medical innovation continues to drip out of AHIP like an incontinent drunk.   I imagine that AHIP's new hired gun Brendan Buck (who has ducked my request to have anyone from AHIP debate me, Scott Gottlieb and a cancer survivor) thinks that repeating a twitter hashtag #timeforaffordability will somehow hynoptise people into believing that health plans would just love, love, love to not jack up the cost of lifesaving drugs (generics and innovator) by 250 percent and not have to limit access to therapies by forcing people to 'fail' (i.e.  get sicker and closer to death) but they can't because all these drugs are so gosh darn expensive.  

Let's ignore the fact that health plans have calculated, down to the penny, that they make more money discouraging people with chronic conditions from using new medicines or enrolling in their plans than they do in performing the mission they claim they pursue: maintaining health and preventing disease.   The claims about drug costs skyrocketing are lies.  Don't take my warped word for it.. Here's the headline from a news release put out by the IMS Institute for Health Informatics..

IMS Health Study: Cancer Drug Innovation Surges As Cost Growth Moderates..

From the study:  U.S. market for oncology drugs has grown at a 3.5 percent CAGR over the past five years, reaching $37 billion last year.  

Total revenues of US health plans in 2013 are estimated to be $432 billion.   In 2008, total revenues were $346 billion.     That's nearly 6 percent a year increase.

Prescription drugs are 15 percent of total health care expenditures paid for by health plans.   They are 13 percent of revenue.   In 2008, Rx was $46 billion.  In 2013 Rx costs were about $56 billion.   That's a 4.3 percent increase.

I know how you are feeling after reading that..  my heart weeps for AHIP too...

Meanwhile, back on planet Earth,  HIV organizations and the National Heath Law Program are suing four health plans for discriminating against people with HIV.   From Brianna Ehley's article in The Fiscal Times:

Obamacare Insurers Hit High-Cost Patients with High Drug Prices

Some insurance companies are finding ways to get around one of Obamacare’s most popular provisions that requires everyone to be covered equally—regardless of any pre-existing condition.

The anti-discrimination rule was meant to guard against insurers who historically charged higher premiums to sick people. But some insurers are still charging certain patients more by passing the extra costs on in the form of higher drug prices.

Meanwhile, the results of a 3 year study show what dozens of others have demonstrated.  Use of new drugs reduce other health care costs.. by a lot.

Changing Physician Incentives for Affordable, Quality Cancer Care: Results of an Episode Payment Model

I'll have more on this study later as well as the befuddlement of the authors who can't believe the results clash with the AHIP propaganda...

AHIP's hashtag should be #AHIP4letterwordforlie. 


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FDA and the First Amendment in the Age of Social Media and Value-Based Reimbursement. What's a regulator to do?

07/09/2014 07:21 AM |

A fascinating, important, and timely analysis from forbes.com.

The First Amendment, In Your Medicine Cabinet

No American in 2014 who watches television, reads a magazine, goes online or visits a doctor’s office can escape the ever-present promotion of prescription drugs. Pharmaceutical promotion, both directly to doctors and to patients, has been the backbone of prescription drug sales for decades, with sales driving everything from drug access to stock prices to research and development.  So what happens when the third largest industry in the United States changes the way it promotes products? We might find out.

Scott Liebman, head of the FDA Regulatory and Compliance practice at Loeb & Loeb LLP explains, “A confluence of events has primed the life sciences industry for a paradigm shift. First Amendment challenges to restrictions on off-label communications, evolving transparency in pricing and payments, the Affordable Care Act and other key regulatory developments are coming together in a way that could fundamentally change the sales of drugs, devices, and biologics in this country.”

The Promotion Paradigm: “Ask Your Doctor About…”

The United States is one of only two nations in the world that allows direct-to-consumer advertising of regulated medical products. It is no coincidence that we also rank as the world leader in pharma research and the world’s largest market for pharmaceuticals.  “In order to protect consumer safety while preserving consumer choice, regulators have developed numerous and rigid standards for promotional communications, especially those related to the marketing or advertisement of drugs off-label, in other words outside of their FDA-approved indication,” says Liebman.

At present, any promotional statements about a prescription product that are inconsistent with the prescribing information in the label are prohibited according to the Food, Drug and Cosmetic Act. Liebman further explains, “Any promotional statement must be accurate, complete, not misleading and balanced with information related to both benefits and risks.” Along with these regulations comes a highly active enforcement system that generates billions of dollars in revenue at the federal and state levels through settlements and penalties.

In reality, many drugs may be effective in treating disease states or patient populations outside their FDA-approved indications, creating the potential for billions of dollars in new sales. The burdensome regulation placed on manufacturer’s speech is not, however, intended to stop doctors from prescribing drugs for any use they believe to be safe and effective. According to a 2006 Stanford study, an estimated 21% of all written prescriptions are for non-primary label use. Dr. Randall Stafford says in his 2008 New England Journal of Medicine article that, “Although off-label prescribing — the prescription of a medication in a manner different from that approved by the FDA — is legal and common, it is often done in the absence of adequate supporting data. Off-label uses have not been formally evaluated, and evidence provided for one clinical situation may not apply to others.” If that is true, however, how are doctors predicating their off-label prescribing decisions?

Off-Label Communications: The FDA Loses Ground In Court

Doctors have access to off-label information from the manufacturers themselves through a legal carve out for scientific communications made in response to an unsolicited request. If a representative provides off-label information without receiving an unsolicited request, however, the communication can be deemed illegal. In 2009, Allergan sued the FDA asserting that the FDA’s prohibition on the dissemination of off-label information violated the company’s First Amendment right of free speech.

At that time, Allergan had allegedly been promoting Botox® for the treatment of migraine and other indications that were not yet approved. The three resulting whistle-blower suits left Allergan facing enormous civil and criminal penalties, so in 2010 it negotiated a $600 million settlement to resolve its liabilities and entered into a Corporate Integrity Agreement that required the withdrawal of its First Amendment complaint.

A mere six weeks later, Botox® received FDA approval for prevention of headaches in adult patients with chronic migraine.

Allergan’s withdrawal left the industry without appropriate jurisprudence to guide decision making about off-label communications. That changed in 2012 when the US Circuit Court for New York decided US v. Caronia, determining that a sales representative for a pharmaceutical manufacturer had the constitutional right to discuss products for off-label uses. The Caronia case raised questions regarding the authority of the FDA, and to date, the FDA has not appealed.  “Although only valid in the Second Circuit, the Caronia case opened the door for additional challenges,” says Liebman.

Since the Caronia case, the FDA revised and reissued a draft Guidance document related to the distribution of scientific and medical publications on unapproved new uses for drugs. Echoing Allergan’s 2009 complaint, the Washington Legal Foundation, a prominent public interest law and policy center, has submitted a comment challenging the Constitutionality of this draft Guidance.

How Much Does That Cost?

Several sections of the Affordable Care Act (ACA) address the cost of healthcare services, including prescription drugs. On the highest level, the ACA intends to shift from a fee-for-service model to a value-based outcomes model. In addition, the law mandates the disclosure of vast amounts of pricing and outcome information. The ACA drew attention to the issue of transparency around the pricing and usage of drugs, such as the costs associated with promotion of regulated products. Further, the FDA recently requested comments regarding use of comparative price information in direct-to-consumer and professional prescription drug advertisements.

“Because of new reporting requirements, a shift toward insurers reimbursing for value to the patient and the ability to make information publicly available online, consumers have an unprecedented amount of information available to make healthcare decisions,” explains Liebman.

The New Consumer

Today’s patient has far better tools to become informed about the prescription drugs available to them. The proliferation of information publically available on the internet has left the FDA racing to issue guidance for the monitoring of interactive media and flooding federal websites with new data sets every month.  This same information is available to health care providers. Patients and physicians alike now have access to everything from peer reviewed journal articles to patient blogs. The industry is seeing the information gap close, creating a new patient-consumer who is able to make complex decisions that balance health and economic considerations. If a $50 injection can be used off-label to treat a patient’s condition with comparable safety and effectiveness to a $500 injection used on-label, wouldn’t price information be of great value in making the decision about which drug to use? More and more, patients have access to that type of information.

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NBCDs -- Not so proud as a peacock

07/07/2014 11:27 AM |

Let’s talk about Non-Biologic Complex Drugs (NBCD). If you look at the FDA’s recent actions relative to raising the issue of quality and performance of generic products and working with outside partners to seriously investigate the problem, you’d think that NBCDs are an obvious top of mind agenda item for the agency to consider and act on via Guidance. But, as with many difficult regulatory questions, predictability comes at the expense of ambiguity – and regulators have a penchant for embracing ambiguity.

When it comes to NBCDs (as with so many other issues), predictability is power in pursuit of the public health.

Friend and colleague Scott Gottlieb pulls no punches in his Forbes column on the FDA’s approach (or lack thereof) to NBCDs.

(For more on the issue see “FDA’s Conditional Response to NBCDs”)

Commentary: FDA's Looming Decision On A Generic To Teva's Copaxone Reveals Drug Approval Woes

Scott Gottlieb

A year ago, the Food and Drug Administration quietly posted a public notice that it wanted to hire an independent lab to test a generic drug that it had already approved. FDA wanted to make sure the drug was safe and effective.

The issue concerned a copy formulation of a complex, intravenous medicine used to replenish kidney-dialysis patients’ stores of iron. FDA had approved this “generic” version of the drug in March 2011 because it believed that laboratory data showed that the replica version of the drug was the exact same as the original branded medicine it was copied from. In announcing the request for independent testing of the generic version, FDA was indirectly saying it might have been wrong.

FDA was going back to get more evidence – including data looking at how the drug was behaving in patients – to make sure that its original decision was sound. Additional evidence was needed because this type of drug represents a new chapter in FDA drug approvals. By law, generic drugs are supposed to contain identical copies of the active ingredient of the original branded medicine that they are copied from. With almost all generic drugs, making identical copies has been relatively easy because the original medicine was a small molecule, which has a simple molecular structure. In contrast, complex drugs involve large molecules and are difficult to copy. In fact, their physical and chemical properties may not be fully understood. Even so, FDA has begun to approve generic copies of complex drugs.

Since approving the generic IV iron medicine in March 2011, FDA has approved several other generic complex drugs, including a generic version of a drug that fights several types of cancer, called Doxil. None have been smooth affairs. At the time it approved that cancer drug Doxil, for example, FDA said it had developed a “novel bioequivalence method” to judge the copy drug same as its branded alternative. Like the case with IV Iron, FDA sought a “post-market” study in 2013 and another one in 2014 to make sure its original approval of Doxil was scientifically sound.

Now, on the anticipated eve of one of the most significant generic drug approval decisions in recent years—involving another complex drug—the lesson from the generic IV iron episode bears reminding. FDA is widely known to be considering the approval of a generic version of Teva Pharmaceutical’s (NYSE:TEVA) blockbuster drug for multiple sclerosis, Copaxone. The patents covering Copaxone for its 20mg/ml strength expired on May 24th. After patent expiration, FDA could approve generic copies of the drug at any time. But some of the same challenges that caused the agency to struggle with and sometimes stumble over its similar previous decisions still linger, and will color FDA’s decision concerning Copaxone.

When it comes to evaluating copies of these complex drugs, the fact is FDA doesn’t have very good tools and policies. These drugs slip between FDA’s other generic drug constructs. They are less complex than biological drugs, which have their own separate law governing how the agency should review and approve copy versions. (Unlike with the generic drug law, the approval of copy versions of biologicals generally must be supported by evidence from human studies.) But non-biological complex drugs are far trickier than generic versions of the normal, small molecule pill drugs that FDA is accustomed to evaluating. It’s that framework for these small molecule drugs that FDA has been trying to apply to these complex drugs.

These challenges illustrate a need to reconsider how FDA approves copy versions of complex drugs. Perhaps different approval standards should be used. Current law already contains an appropriate alternative to the generic drug law in the pathway used for the review and approval of copies of biological drugs, which gives FDA more latitude when it comes to the data it can use as a the basis for these approvals. Some of these principles could be applied to a new category that addresses the complex drugs. Or Congress could re-write certain aspects of the generic drug law, tailoring generic drug principles to the unique challenges of copying complex drugs.

FDA also needs to change its practices when it comes to these complex drugs, to more clearly establish reliable principles for how generic copies of these medicines can be safely brought to market once brand-name patents have expired. It needs to develop these scientific principles in a more transparent and inclusive process that leverages the expertise that FDA doesn’t readily posses to discern these laws of drug science. More on these policy challenges, and their potential resolutions later.

The complex drugs fall in a regulatory gap. FDA has tried to retrofit the “Hatch Waxman” generic drug law and policies that govern approval of small molecule drugs to these complex drugs, with sometimes troubling results. Regardless of the decision FDA makes with Copaxone, it remains clear that Congress and FDA alike need to re-examine the regulatory process when it comes to these intricate drugs.

The problem is that FDA has refused to define these complex drugs as distinct from normal, small molecule medicines. That has forced the agency to rely on less information in approving these complex copies than it probably would like. The agency’s desire to try and squeeze these complex drugs through its existing generic law approval pathway may have as much to do with political expediency as with good science. FDA is probably well aware that getting Congress to define a distinct category for these medicines, and give FDA proper tools, could be a heavy political lift. So FDA is doing what it often does: trying to massage its existing authorities and regulatory practices to fit novel challenges. But at what cost?

These non-biological complex formulations are different than small molecule drugs. As a result, they don’t fit the standard paradigm on which copy (generic) versions of branded drugs are typically reviewed and approved by FDA.

To approve a generic drug, the generic drug law and subsequent regulations discourage FDA from asking for data other than bioequivalence data. As a result, these generic drug approvals typically rely on “pharmacokinetics” data that shows that the copy drug gets into the blood in the same predictable fashion as its brand-name alternative. But for complex intravenous drugs, the behavior of the medicine often depends on aspects of the mixture that are hard to copy and even harder for FDA to fully characterize (i.e., understand the physical and chemical properties). Like the IV iron formulations, Copaxone is a complex drug – perhaps more complex than any drug of this type, where FDA has been asked to review copies. When it comes to these drugs, looking at bioequivalence data alone can be insufficient to tell how the drug will behave once it’s administered to the patient.

So sometimes the agency cheats a little. At times it has looked at human testing data after the fact, to make sure it didn’t err (as was the case with the generic IV iron medicines). Other times, FDA tries to expand the scope of what it can include in a generic application. This was the case when it came to the approval of generic versions of the blood-clot prevention drug, Lovenox. In that example, FDA looked at human data to make sure the two drugs didn’t cause different reactions from the body’s immune system. (FDA was accused of exceeding its authority under the generic drug law and was sued for this, but ultimately prevailed in court because the courts give great deference to FDA. Interestingly, Europe regulates generic Lovenox as a biological product, which means that evidence from human studies is required)

Copaxone is an especially hard case, because the drug’s benefits are thought to turn on the complexity of the mixture, which isn’t well understood.

The drug exits as a complex mix of long and short chains of carbohydrates. It is believed that the precise proportion of these long and short chains in the solution is tied to the drug’s therapeutic attributes. But making sure that a copy batch of the drug can reproduce the same quantity of long and short chain carbohydrates, in the same proportion, isn’t straightforward. And the generic drug law effectively bars FDA from looking at evidence from human studies to see if the copy is working as well as the brand-name alternative. For the most part, all FDA can do is examine data comparing the two solutions, and how they get into the blood (bioequivalence data). But FDA can’t look at how the generic version affects outcomes in patients.

So in the case of Copaxone, for example, FDA is widely believed to be considering gene expression data that shows how the drug turns on and off the function of certain genes. The genes FDA is looking at are thought to be involved in regulating how the drug modulates the immune system in multiple sclerosis. If FDA is relying on this sort of gene expression, it would be largely because FDA needs to find some potential surrogate marker in lieu of full comparative clinical endpoint studies, which FDA can’t ask for under the generic drug approval process. But here again, FDA would be creating brand new scientific criteria by establishing that the gene expression data can stand in for clinical outcomes data. These aren’t just review criteria that FDA is establishing in the context of its struggle with this particular application, and its desire to find a way to prove “sameness” based on laboratory testing data (so that it can approve the generic Capaxone). By relying on the gene expression data, FDA is establishing what should be immutable laws of drug science. Using the twists and turns of a meandering and secretive generic drug review is not the right place to be establishing these sorts of generalizable scientific principles.

To these ends, the challenge isn’t just the generic drug law, which doesn’t allow FDA to look at much more than bioequivalence data. The setback is what FDA has done in response to these limitations, to try and retrofit its existing policies on complex drugs where the generic drug principles are sometimes poorly suited. And FDA has entered this new chapter in generic drug approvals largely under the radar. Congress and the public generally are not aware of the new direction FDA is taking.

Instead of acknowledging that it needs a broader scope of data to ensure “sameness” (the statutory standard for a generic drug approval) between the original and the copy drug, FDA has typically divined new science in these circumstances – coming up with novel principles of drug science to determine how two drugs can be declared the same by comparing laboratory data that FDA often establishes on its own novel principles. Such is the case with the gene expression data that FDA is examining in the case of Copaxone. FDA will typically announce these new principles after the fact, often at the time of approval of the generic drug.

Problem is FDA doesn’t do this sort of science well. Establishing new principles on which sameness can be determined between complex formulations of drugs is something that requires expertise in these fields. FDA is in the business of evaluating data against known standards, not establishing those standards de novo. The enterprise of establishing standards upon which two highly complex drugs can be judged the same requires a great deal of expertise in discrete areas of science. This sort of expertise doesn’t exist in one place, and certainly isn’t the province of FDA. That’s not a knock on FDA, or its scientists. This sort of work just isn’t the business that Congress has tasked the agency with doing. FDA is not staffed or resourced to take on the task of developing novel principles of biology and discovering the standards for measuring how drugs affect biological systems.

As a result, FDA has often established principles that are at times embarrassingly incomplete, and sometimes spectacularly wrong. The re-adjudication of the generic IV iron approvals is one example. The problems FDA had in 2008 assuring safety and effectiveness of generic, copy versions of intravenous heparin is another example. FDA had to recently walk back guidance it put out on how to copy a popular eye drop that was another complex formulation. In each case FDA had established some principles upon which the agency thought it could reliably determine that two complex drugs were the same. In each case, FDA was wrong.

When it comes to certain complex drug formulations, Congress may need to update the law to give FDA broader discretion to use a larger complement of information to make sure that a copy version of a drug is the same as its branded counterpart (while still enabling the copy to be approved as a generic, fully substitutable medicine). If FDA had such latitude, it could actually speed generic entry of these complex drugs. Right now, each approval has been a long and tortuous process that often extends well past the expiry of legitimate patents. Congress, for example, crafted specific legislation when it came to copies of biological drugs. It recognized that the generic drug law did not adequately address how to develop and approve copy versions of these highly complex drugs. Right now, the non-biological complex intravenous drugs fall within a gap between the existing small molecule (pill form) medicines and the highly complex biological medicines. Neither approval pathway seems to address copy versions of non-biological complex medicines well.

But there’s another problem. This one is of FDA’s own making. In cases where FDA believes that the existing generic drug framework already gives it ample discretion, FDA needs to adopt a more transparent and inclusive process for developing the scientific principles upon which it makes these judgments. This sort of process ends up establishing final principles of drug science. Rather than these principles being divined through regulatory fiat, they need to be established in an open scientific process that readily draws on all of the available expertise in adjudicating these principles. FDA workshops and advisory panels could provide a forum for these discussions, should FDA choose to use them.

Moreover, FDA needs to generalize these principles in guidance, preferably well in advance of patent expirations that create the opportunity for generic entry. These standards, once established, often end up affecting many different kinds of generic drug approvals. By establishing them in an open process, FDA would make this important knowledge generally available, and would lower the barrier to market entry by generic firms of different levels of technical sophistication. It should be emphasized that FDA’s current lack of transparency makes it hard for many generic-drug companies to get on the playing field. The big companies, that have more access to FDA’s thinking, end up being advantaged over smaller generic players that don’t have this proximity. Transparency could promote generic competition.

In the case of the IV iron drugs, even after approving generic copies of these medicines, FDA went back in 2013 and commissioned research to develop a methodology for how it could determine sameness between a brand name and generic formulation of IV iron. It begs the question, what criteria were FDA using all along when it approved generic copies of these drugs? The scientist who received that award issued a press release referring to her work as “uncharted territory”.

The consideration of a generic version of Copaxone is being closely watched as, among other things, another indication of how permissive FDA has become in approving these generic complex formulations. In the past, the answer seemed to be as permissive as FDA needed to be in contorting rules of law and science to advance these approvals. It shouldn’t be that way. Congress should be tapped to give FDA the latitude to look at the science necessary to make comfortable and reliable determinations. The broader scientific community should be leveraged, through open dialogue, to give FDA the princi   Read More & Comment...

Strategic Thinking for a Strategic Sector

07/03/2014 06:29 AM |

A new European Commission working paper positions the pharmaceutical industry at the heart of the region’s economic growth prospects. 

Pharmaceutical Industry: A Strategic Sector for the European Economy (available here) marks a significant turning point towards an integrated life sciences strategy for Europe. The working paper takes stock of the sector’s current situation, focusing on developments made over the last years as the first step in preparation for a new strategic agenda.

The paper highlights several points for strategic focus including: 

• The presence of a viable pharmaceutical industry contributes to the health and the quality of life of citizens by providing remedies to an increasing number of patients, through a more timely, widespread and equal access to pharmaceuticals.
• Intellectual property rights related to pharmaceuticals have gained prominence in debates about intellectual property rights policy. They have been at the forefront in discussions about the impact of intellectual property rights in terms of the access to medicines, particularly in developing countries. In the light of these divergent views, European companies are often faced with significantly lower levels of intellectual property protection in third countries, particularly in emerging economies. The challenges range from a lack of or non-enforcement of patents to the disclosure or reliance on data submitted by the original manufacturer for obtaining a marketing authorization by regulatory authorities, thus depriving companies of the economic benefits of their investments.
• Assessing pharmaceutical expenditure also requires taking into account the effects on other health-related costs (like hospitalization, sick leave, pensions, etc.) as well as the overall implications for industrial competitiveness and external trade.

The paper suggests a comprehensive approach to streamlining the policy formulation processes impacting the pharmaceutical industry at European and Member States level. Against this backdrop, the European Commission will organize an event bringing together relevant EU and national public and private stakeholders: decision-makers from public bodies in charge of industrial competitiveness, health, pricing and reimbursement, research and innovation at Member States level, and their Commission counterparts, patients, healthcare professionals, trade unions and industry representatives. 

The strengthening of the competitiveness of the European pharmaceutical industry requires actual implementation of innovation policies at EU and Member States level in order to create incentives and rewards for a sustainable, competitive pharmaceutical sector that addresses public heath needs.

On the intellectual property rights front, more than half of EU industries are considered IPR-intensive, providing for 35% of European jobs and 39% of total economic activity. It is crucial to ensure a strong and effective framework for IP protection and enforcement if we are to preserve the ability of EU industries to adequately grow and export. This also implies raising awareness as to the critical need for IP.  

In related news, the new EU Action Plan of DG MARKT addresses infringements of intellectual property rights in the EU, strengthens the enforcement policy framework against commercial scale IP infringements, by defining a set of 10 innovative actions and tools. This action plan notably embodies the "follow the money” approach, which deprives infringers of their revenues. 

The revised Strategy of DG TRADE for the protection and enforcement of IPRs in third countries rightly accounts for the current challenges which right-holders are faced with when trying to protect or enforce their intellectual property rights abroad. Addressing specifically the challenges of access to medicines worldwide, this new strategy recalls there are "many factors affecting access but mostly unrelated to IPRs". The Commission highlights the need to come up with a broad response to this complex and multifaceted problem, to ensure affordable access to medicines without undermining the incentives needed for continued pharmaceutical research.

The Commission documents are must-reads for all health and finance ministries from Pretoria to Beijing, to Delhi and elsewhere as they debate and consider the future roles of both IPR and strategic collegiality in the realm of pharmaceuticals and the public health.

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Regulatory Science Ho!

07/02/2014 06:25 AM |

I don't care what anyone says -- the FDA has its priorities straight.

(At least on paper.)

As reported in BioCentury, FDA has released a draft four-year plan for 2014-2018 that reiterates its emphasis on advancing regulatory science. The agency said it plans to increase the use and capacity of regulatory science -- which it defines as the science of developing tools, standards and approaches to assess the safety, efficacy, quality, toxicity, public health impact or performance of a food or medical product -- to inform standards development, analysis and decision-making and to effectively evaluate products.

In the agency's strategic priorities for 2011-2015, the advancement of regulatory science was listed as the top priority for the agency as a whole. FDA has since published a strategic plan for regulatory science, which details eight priority areas and calls on the agency to collaborate with stakeholders to develop and refine clinical trial designs.

Other priorities include addressing globalization; advancing safety and quality by reducing risks in the manufacturing, production and distribution processes; strengthening detection and surveillance of problems; and improving response to identified and emerging problems. The agency said it intends to increase the exchange of information with foreign sources by assembling global coalitions of regulators. Earlier this year, the agency launched an initiative to exchange information with EMA and the European Commission on foreign inspections, building on a three-year pilot launched in 2012. Comments are due July 31.

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Abuse Deterrent Opioids: Don't Fix the Blame, Fix the Problem

06/30/2014 07:17 AM |

How important is the issue of opioids? Well, important enough that it was the very first panel offered at the 2014 BIO Convention’s regulatory affairs track. And it didn’t disappoint.

Moderated by yours truly, I was joined by three experts (Douglas Throckmorton, MD, Deputy Director of Regulatory Programs, FDA’s Center for Drug Evaluation and Research, Richard C. Dart, MD, PhD, Director of the Rocky Mountain Poison and Drug Center, and J. David Haddox, DDS, MD, Vice President of Health Policy for Purdue Pharma, L.P.) and a room full of engaged and inquisitive attendees. The session began with a question – Who lost opioids?

I reminded the audience of the old public relations maxim that, “Everything you read in the newspaper is true – except for those things you know about personally.” And today that means the preeminence of social media. Google “opioid abuse deterrence” and you’ll find a lot of hits from lawyers and elected officials in the mainstream media -- but you have to know where to look (or who to ask) to access expert thinking from the FDA.

There’s certainly no dearth of verbiage and suggested solutions from the law enforcement community. Alas, those fixes rely on the general philosophy that the only good opioid is a recalled opioid. And that results in strategies that require strict prescribing limitations, and severely limited access. Punishing the legitimate pain patient, all the panelists agreed, is the wrong way to go.

Then there’s the legislative solution – but what this really means is allowing politics to drive the agenda. The posturing and hyperbole that has surrounded the issue of opioids pain medicines hasn’t resulted in a single workable solution. And the premature promptitude of many attorneys general and chief executives such as Massachusetts Governor Deval Patrick has led to numerous headlines but, in the end, nothing but fruitless lawsuits.

As Mark Twain quipped, “For every complex problem there is usually a simple answer – and it is usually wrong.” What those seeking to solve the problem with one-shot solutions have ignored is that pain in America is a medical problem of enormous proportion.

100 million Americans are now living with chronic pain. That’s a third of the U.S. population. Ten million of those have pain so severe that the pain disables them. Pain costs the US economy about $600 billion dollars a year in lost productivity and healthcare cost. And lawsuits, recalls, and police actions won’t change those dire statistics.

But just as opioids aren’t the problem, neither are they a panacea. Yet payers often implement barriers to the use of branded, on-label non-opioid pain medicines, relegating these treatments to second line options. 52% of patients diagnosed with osteoarthritis receive an opioid pain medicine as first line treatment, as do 43% of patients diagnosed with fibromyalgia, and 42% of patients with diabetic peripheral neuropathy.

Aren’t abuse deterrent opioids the magic bullet we’ve all been looking for? Not really. First of all, what does “abuse deterrence” even mean? As FDA Commissioner Peggy Hamburg testified to Congress, “It doesn’t do any good to label something as abuse deterrent if it isn’t actually abuse deterrent, and right now, unfortunately, the technology is poor.” Abuse deterrence is a goal. And at present, it’s an elusive one.

Abuse deterrence also raises some very important and difficult regulatory questions for the FDA. What type of 21^st regulatory science will be required to review abuse deterrent applications? How will the agency approach the approval of non-abuse deterrent generics? What about more sophisticated pharmacovigilance programs? And, last but not least, how can the FDA better protect the public health while simultaneously preserving innovative development programs?

Dr. Throckmorton’s presentation noted that both FDA and other government epidemiologists are working to improve the surveillance databases and tools used to assess impact of abuse deterrent formulations in US market. He specifically mentioned the  “DAWN” (Drug Abuse Warning Network) database replacement, measuring appropriate access to opioids by pain patients. The development and broad adoption of successful abuse-deterrent formulation remains an important priority for FDA. But we’re in the early days of the science, with much important work to be done.

But what else can be done?

As former Canadian Prime Minister Pierre Trudeau once said, “There's no place for the state in the bedrooms of the nation.” But what’s the appropriate place for the state in our nation’s pharmacies and medicine chests – particularly for opioids? As CDER Deputy Director (and the FDA’s point-man on opioids) Dr. Douglas Throckmorton said, “We are challenged with determining how to best balance the need to ensure continued access to patients who need these medications while addressing concerns about abuse and misuse.”

While scene-stealing members of Congress, some governors, and a gaggle of state attorneys general are trying to run roughshod over science-based regulation to great attention from the media, the FDA has been quietly doing the right thing without anybody noticing. In the immortal words of Don Draper, “If you don't like what is being said, then change the conversation.

The FDA must play a lead role in facilitating physician education, not only through labeling language but physician education. The FDA has, of late, repeatedly discussed enhancing continuing medical education (CME) and working to develop (with a broad constituency) validated tools for physicians to use in determining which patients may be more prone to slide into abuse so they can choose their therapeutic recommendations more precisely.

In the words of FDA Commissioner Hamburg, “It all comes back to provider education.” Amen.

Provider education – the Hamburg Manifesto.

That’s not regulatory mission creep; it’s the appropriate application of the agency’s Safe Use of Drugs initiative. The way you make a drug “safer” is to ensure that it is used by the right patient in the proper manner.

Abuse deterrence is a worthy goal and will evolve when all the players work together in a more regular and synchronistic fashion. Fortunately, all panelists agreed this was the reality.

As the Japanese proverb goes, “Don’t fix the blame, fix the problem.”

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MASS confusion

06/27/2014 08:55 AM |

The Massachusetts Senate has passed legislation to allow pharmacists to substitute a biosimilar for a biological medicine when the United States Food and Drug Administration has determined that the two biological products are interchangeable and the prescriber has not instructed otherwise.

Following a substitution, the bill requires pharmacists to notify the prescribing practitioner and the patient. The bill will now go to the Governor for his signature.

Sounds good, right? Physician notification. But the bill was obviously drafted before the FDA expanded the types of biosimilars it will consider. Once upon a time there were two categories: biosimilar and interchangeable. But today there are four: not similar, similar, highly similar or highly similar with a fingerprint-like similarity -- depending on the type, nature and extent of any structural and functional differences revealed.

The reality is that “interchangable” is a thing of the past – even before it was a thing of the present.

In keeping with the spirit of the Massachusetts legislation (as well as that in many other states), the nomenclature should be reconsidered to reflect the realities of the evolving regulatory science.

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The Patient Voice Speaks! (And not in anecedotes)

06/26/2014 01:18 PM |

When it comes to the patient voice (or any voice), the plural of anecdote isn't data. But the plural of data is science.

First-Ever Patient-Initiated “Guidance for Industry” for Duchenne Muscular Dystrophy Submitted to FDA

Parent Project Muscular Dystrophy-led guidance seeks to address unmet clinical needs of individuals with Duchenne muscular dystrophy and accelerate development of safe and effective therapies

Washington, DC–June 25, 2014 -- Parent Project Muscular Dystrophy (PPMD) and a broad coalition of stakeholders today submitted the first-ever patient advocacy-initiated draft guidance for a rare disease to the U.S. Food and Drug Administration (FDA) to help accelerate development and review of potential therapies for Duchenne muscular dystrophy (Duchenne).

“This landmark guidance represents a major milestone for the Duchenne community and may open the way for other rare disease groups to incorporate the patient perspective in a well-documented and quantifiable way, moving beyond any one family’s experience,” said PPMD President Pat Furlong. “By working closely with the FDA to provide industry and other clinical trial sponsors with clearer guidance from the patient perspective, we will increase the likelihood that clinical trials will be designed to better match the unique needs of Duchenne patients. It is our profound hope that this, in turn, will lead to the approval of much needed treatments for all people living with Duchenne muscular dystrophy.”

Duchene, the most common lethal genetic disorder diagnosed in childhood, is a progressive and degenerative condition with no cure or disease-modifying treatments available in the United States.

Clinical trials for rare diseases like Duchenne are difficult to design and implement because of challenges such as small study populations, incomplete and evolving understanding of rare diseases, and effective ways to measure clinical impact of therapies being studied. Last year, FDA collaborated with PPMD and its scientific advisors to convene a policy forum that informed the process for developing the Duchenne community’s suggested guidance.

“The U.S. Food and Drug Administration is appreciative of the input of Duchenne patients and patient advocates. Their input will enhance the essential data-driven process and evaluation of new therapies,” said Janet Woodcock, M.D., Director of the Center for Drug Evaluation and Research at the U.S. Food and Drug Administration.

About The Suggested Guidance

More than 80 representatives of the Duchenne community - including parents and patients, medical experts, academics, and biopharmaceutical industry representatives -- participated in seven working groups that met over the past six months to draft the guidance.

The cornerstone of the guidance encourages the FDA and trial sponsors to engage patients and their families at all stages of trial development and to take into account what they consider acceptable risk in clinical trials. A recent PPMD study published in the journal Clinical Therapeutics* shows that parents of children with Duchenne will accept substantial risk when balanced with noncurative slowing or stopping of the progression of muscle weakness, even with no improvement in life expectancy. The results came from the first-ever scientific survey of benefit/risk perspectives that PPMD conducted last year involving 120 Duchenne parents.

“As the FDA evaluates new drug applications for Duchenne therapies, it is imperative to take into consideration the value that parent decision makers place on even moderate benefits to function and mobility, and their tolerance for considerable risk and uncertainty,” said Furlong. “Parents and caregivers of Duchenne children know firsthand that every day without treatment is another day closer to their child losing essential activities of daily living such as walking, feeding oneself, and eventually, breathing. When your child is living with Duchenne, you find yourself willing to take significant risk for even the hope of modest benefit. Parents can make these decisions thoughtfully and the FDA must recognize that. They cannot protect us from what we think is important in the drugs we need now.”

Each section of the guidance includes extensive published or in-press peer-reviewed articles and focuses on six areas aimed at overcoming the challenges in trial design and implementation:

* Benefit/Risk Assessment – providing a community-centered approach for the benefit-risk framework fundamental to the regulatory process and reflecting the community’s tolerance of potential risks or uncertainty of benefit associated with new treatment options.

* Diagnosis – referring sponsors to guidance produced by the American Academy of Pediatrics (AAP) on a diagnostic algorithm, as well as, providing context on diagnostic delay and importance of genetic analysis using modern technologies, including access to genetic testing.

* Natural History – accurately characterizing the clinical course of Duchenne to reflect the timing of the loss of certain abilities based on current medical management practices, including how Duchenne affects cardiac and pulmonary function.

* Clinical Trial Designs, Outcome Measures and Considerations – ensuring that trials – to the degree possible – are inclusive of Duchenne patients of all ages and disease stages.

* Muscle Biopsy-Based Biomarkers – addressing key considerations when performing muscle biopsies, including the ethical imperative to perform them only when needed and precautions to assure usable specimens; sponsors are also referred to an international effort to standardize methodologies and emerging technologies.

* Non-Muscle Biopsy-Based Biomarkers – exploring the ability to bring non-invasive imaging techniques to replace biopsy (e.g., MRI/MRS skeletal muscle imaging) and eventually reach the goal of being a surrogate endpoint for treatment trials.

PPMD-Led Efforts

The suggested FDA guidance represents the culmination of PPMD’s 20 year history of improving care and developing urgently needed therapies for Duchenne. PPMD led the effort to pass the MD-CARE Act, which created the Senator Paul Wellstone Muscular Dystrophy Cooperative Research Centers. The draft guidance builds on PPMD’s effort to shape federal policy that reflects the needs of families living with Duchenne, including the release of “Putting Patients First” which calls on the FDA to act more flexibly when reviewing applications for Duchenne therapies. PPMD also ensured that the FDA Safety & Innovation Act of 2012 (FDASIA) responded to the needs of the community; recently published a groundbreaking benefit/risk study which documented the willingness of families to live with risk; and held a national PPMD-FDA Duchenne Policy Forum where the community made its needs and preferences in drug development known to the Agency.

*[EDITOR’S NOTE – Peay H.L. et al: A community-engaged approach to quantifying caregiver preferences for the benefits and risks of emerging therapies for Duchenne muscular dystrophy; Clinical Therapeutics, Vol. 36, No. 5, 2014; available for access: http://www.clinicaltherapeutics.com/article/S0149-2918(14)00209-4/abstract.]

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The Cost of Quality

06/25/2014 10:53 AM |

The New York Times has written quite a lot lately on the cost of drugs – without a word on either the value of new medicines or the cost of investing in innovation. On the up side, the Gray Lady has finally discovered the cost of poor medicines quality.

For years, Dr. Harry Lever, a cardiologist at the Cleveland Clinic, has been warning nearly anyone who would listen of his growing suspicions about generic versions of a widely used heart drug, Toprol XL.

Patient after patient, he said, would visit his office complaining of chest pains or other symptoms after switching from the brand-name version, made by AstraZeneca, to a generic product, often one made in India. When he switched them back to the brand — or to another generic — the symptoms disappeared, he said. Dr. Lever wrote a letter outlining his concerns to the Food and Drug Administration in 2012, and this year, he traveled to Washington to try to get the attention of Congress.

Dr. Lever could not prove that the generic drugs were to blame. “You see enough people and you get a feel, but it’s anecdotes,” he said in an interview Monday. “It’s not science.”

This is in keeping with a March Reuter’s story on the same topic:

Some U.S. doctors are becoming concerned about the quality of generic drugs supplied by Indian manufacturers following a flurry of recalls and import bans by the Food and Drug Administration.”

"I'm just beginning to realize the gravity of the problem," said Dr. Steven Nissen, head of cardiology at the Cleveland Clinic. "It's terrible and it is starting to get a lot of traction among physicians."

Hopefully the Times story will provide further traction because, as Dr. Lever said (in the Reuter’s story),

We are losing control over what people are swallowing," said Dr. Harry Lever, a cardiologist at the Cleveland Clinic who is trying raise awareness of the matter among U.S. lawmakers. "Now, when a patient comes in who is not doing well, the first thing I do is look at their drugs and find out who makes it."

It’s too simplistic to call these “quality” problems. There’s a range from sub-standard API and manufacturing issues, to excipient changes and, most importantly, bioequivalence and bioavailability standards.

Bioequivalence does not always equal therapeutic equivalence – and that’s as true for Toprol XL as it is for Wellbutrin. According to the Times story, Two large Indian manufacturers, Wockhardt and Dr. Reddy’s Laboratories, have announced recalls over the last two months totaling more than 100,000 bottles of Toprol XL because their products were not dissolving properly — therefore probably not working as they should. The drug is a beta blocker that treats high blood pressure and heart ailments. Not good.

FDA’s recent draft guidances on bioequivalence for both generic and innovator products, as well as the move towards independent labeling for generic products are additional steps the agency has recently taken to address the issue of drug quality beyond safety and efficacy. And the implications for biosimilars is obvious

(Something else to consider is for the FDA to report BE and BA and PK data in generic labels.)

Small is the new Big means we must think differently about pharmacovigilance. While we must continue to capture adverse event data, we must also strive to capture Substandard Pharmaceutical Events (SPEs). SPEs occur when a product does not perform as expected—perhaps because of API or excipient issues. SPEs can arise because of an issue related to therapeutic interchangeability. When it comes to 21st-century pharmacovigilance, we have to both broaden and narrow our views about bioequivalence to the patient level.

Where's the Times editorial on that?

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BIO Bound

06/22/2014 09:32 AM |

My bags are packed. I’m ready to go.

As many of us head out to San Diego for BIO, it’s important to put the gathering in the proper perspective. It’s not just about business. It’s not just about networking. It’s about advancing the public health. It’s about protecting and advancing innovation.

Attached is a letter that Pfizer honcho Ian Read just sent to Representative Fred Upton. Mr. Upton, as you are likely aware, is the Chairman of the House Committee on Energy & Commerce and has been leading a series of hearings on 21st Century Cures.

Ian also attached a more complete thought piece on a series of innovation priorities. Innovation? Read all about.

While at BIO I’ll be participating in two panels.

The first: Will Government and Payor Policies Encourage Innovation and Create Incentives for the Continued Development of Abuse Deterrent Formulations and Improvements to Existing Technologies in the Regulatory Review and Approval Track?

Panelists

Peter Pitts, Moderator, President and co-founder, Center for Medicine in the Public Interest

Douglas Throckmorton, MD, Deputy Director of Regulatory Programs, FDA’s Center for Drug Evaluation and Research

Richard C. Dart, MD, PhD, Director of the Rocky Mountain Poison and Drug Center

J. David Haddox, DDS, MD, Vice President of Health Policy for Purdue Pharma, L.P.

WHERE: San Diego Convention Center Room 31 B

WHEN:   Tuesday, June 24 2014, 9:00 am –10:00 am

The second: Thriving Again in 2014: Preparing for Success, Not Just Survival at FDA Advisory Committee Meetings

Panelists

David Schull, president of Russo Partners

Penny Daniels, strategic communications consultant at 3D Communications

Craig Audet, Ph.D., senior vice president, operations and head of global regulatory affairs with Arena Pharmaceuticals, Inc.

Peter Pitts, president and co-founder of the Center for Medicine in the Public Interest and former FDA associate commissioner of external affairs

Silvia Taylor, senior vice president, investor relations, public relations, and corporate communications at Sucampo Pharmaceuticals, Inc.

WHERE: San Diego Convention Center Room 31B

WHEN:   Tuesday, June 24 2014, 3:00PM – 4:00PM

In addition, the Center for Medicine in the Public Interest will have a booth. It’s #5642. And we’ll be talking about innovation. 

Hope to see you there.

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Biosimilar Naming: Blackwhite and read all over

06/20/2014 09:57 AM |

Urban legend attributes the following quote to Albert Shanker, the very outspoken past president of the American Federation of Teachers:

“When school children start paying union dues, that’s when I’ll start representing the interests of children.”

As always, it’s a question of priorities – and whose priorities. Today that same issue has arisen in the debate over biosimilar nomenclature.

The issue for drug compendia stakeholders (among other things) is interoperability.

According to Inside Health Policy:

“While some say an easy solution is to simply add a suffix to distinguish a biosimilar from the innovator product, the compendia group told FDA any change is a change, and regardless of the simplicity of the change, the associated coding would also have to shift. First data bank and two other databanks are sold to stakeholders who assemble them and put overlays on them and then the data are used for different purposes, including for reimbursement.”

Yes, well unfortunately change is not always easy. But as management guru W. Edwards Deming warned, “Change is not required. Survival is not mandatory.”

Assigning differential naming to biosimilar products will certainly prove challenging to the various constituents of the drug compendia community – but it will be crucial for pharmacovigilance. In the real world, how can we not have separate names when there are going to be four categories of products?

Based on comparative analytical data, FDA will characterize its assessment of biosimilarity into one of four levels -- not similar, similar, highly similar or highly similar with a fingerprint-like similarity -- depending on the type, nature and extent of any structural and functional differences revealed.

Additional pharmacologic studies would be required to show that the identified difference is "within an acceptable range to consider the proposed biosimilar product to be highly similar to the reference product." FDA said only products in the top two tiers would meet the statutory requirement for analytical similarity under the Biologics Price Competition and Innovation Act of 2009. Products in the top two tiers would then only require "targeted and selective animal and/or clinical studies to resolve residual uncertainties" to demonstrate biosimilarity. In addition, these data could be used to extrapolate clinical data for additional indications.

Giving credit where credit is due, the good people at the USP understand that interoperability is important, but that naming is more of a philosohpical issue. That's why they support differentiation via discrete numerical suffix.

Per Inside Health Policy:

The drug compendia stakeholders told a group of 13 FDA drug policy experts, including drug center chief Janet Woodcock, that changing the traditional naming process would require that each piece of the compendia process be individually rebuilt in order to ensure patient safety and restore functionality to the system. Doing so, while possible, would be difficult and could lead to confusion, errors and misunderstanding, creating a "very real risk to patients," according to slides presented at the May 2 meeting and a June 6 follow-up letter, obtained by Inside Health Policy.

The argument that differential naming is bad for patient safety is pure Orwellian Newspeak -- specifically “blackwhite,” The ability to accept whatever "truth" the party puts out, no matter how absurd it may be.

When it comes to biosimilar nomenclature, it’s urgent that we keep our priorities straight. And that means keeping patient safety, not interoperability challenges, at the top of the agenda.

Fortunately, White Oak trumps blackwhite.

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NoFocus from FDA on social media -- and it's about time!

06/17/2014 11:50 PM |

Per FDASIA: By July 9, 2014, FDA must issue guidance describing FDA policy regarding Internet promotion, including social media, of medical products regulated by FDA.

Well, ahead of schedule we now have two draft guidances:

Guidance for Industry Internet/Social Media Platforms with Character Space Limitations — Presenting Risk and Benefit Information for Prescription Drugs and Medical Devices

And:

Guidance for Industry Internet/Social Media Platforms: Correcting Independent Third-Party Misinformation About Prescription Drugs and Medical Devices

First let’s discuss “Social Media Platforms with Character Space Limitations.

Perhaps the biggest leap forward for the agency is that is beginning to differentiate between social media platforms, recognizing that different rules must apply for different types of platforms. Obviously, when it comes to platforms such as Twitter the main issue is character limitations. The agency also points out that the same is true for advertising venues such as banner ads on Google (shades of the FDA’s first batch of warning letters from 2009).

So, to the FDA’s credit, it only took the agency about five years to develop draft guidance. Not a badge of honor.

Still, there are some interesting things to be gleaned from the draft guidance. The agency writes:

Risk information should be comparable in content and prominence to benefit claims within the product promotion (i.e., a balanced presentation). Achieving a balanced presentation requires firms to carefully consider the desired benefit claims and risk profiles for their products when choosing a promotional platform.

That’s good advice – choose the platform that best suits any given communications need. But, it’s not really any communications need – it’s any promotional program. That’s important because promotional speech is regulated speech. And that’s not just regulatory rhetoric. And this begs a crucial question not covered in the draft guidance – What it the intent of the communications?

Don’t wait for the FDA to offer guidance on that. They will not and should not. That’s a question only the communicator can answer. And it needs to be done honestly and early in the communications development process.

The agency writes:

FDA acknowledges that Internet/social media platforms associated with character space limitations may pose challenges for firms in providing a balanced presentation of both risks and benefits of medical products, as discussed above … The firm should also provide a mechanism to allow direct access to a more complete discussion of the risks associated with its product.

In a likely unintended nod to self-deprecation, the agency offers potential examples of how this could be done for the fictitious product NoFocus.

The agency writes:

A firm is considering promotion of its prescription drug NoFocus on Twitter …  NoFocus is indicated for mild to moderate memory loss.

The draft guidance suggests that the tweet contain the following 40 characters:

NoFocus for mild to moderate memory loss

The agency writes:

The benefit information for NoFocus that is communicated within the first 40 character spaces of this tweet is accurate and non-misleading and includesmaterial facts about the indication and limitations to the use of NoFocus.

So, the agency is also suggesting that these 40 characters be the first 40.

The agency then proceeds to discuss paid search advertising for the fictitious product Headhurtz. (This is likely the product in development for legal and regulatory review departments at pharmaceutical and medical device companies.)

The agency suggests that information on limitations and appropriate use as well as a link to the product website be included. Specifically:

Headhurtz [www.headhurtz.com] For severe headache from traumatic brain injury

It’s not Brief Summary, it’s Tweet Summary.

The agency’s most important advice appears on Page 12 of the draft guidance:

In communicating risk information on Internet/social media platforms with character space limitations, firms should consider the following points:

1. Risk information should be presented together with benefit information within each individual character-space-limited communication (e.g., each individual message or tweet).

2. The content of risk information presented within each individual character - space-limited communication should, at a minimum, include the most serious risks associated with the product.

3. A mechanism, such as a hyperlink, should also be provided within each individual character-space-limited communication to allow direct access to a more complete discussion of risk information about the product … the Agency recommends that a direct hyperlink to a landing page that is devoted exclusively to comprehensive risk information about the product be initially included within the original character-space-limited communication.

Not rocket science, but urgently important to remember when considering both the design and appropriateness of a limited-character platform. Also, the use of hyperlinks is crucial – and will be even more so as we move on to a discussion of the second of the agency’s newly minted draft guidances. (Note – the agency makes it clear that a link’s name should also be considered. Specifically, it shouldn’t be a claim (i.e., www.bestcancercuredrug.com).

Per the new “Tweet Summary,” the agency writes:

Since benefit information was provided within the tweet (example 1A), the firm should communicate, at a minimum, the most serious risks associated with NoFocus within the same tweet. The firm should also include within the same tweet a direct hyperlink to a more complete discussion of risk information about NoFocus. Additionally, the prominence of risk information should be comparable to the benefit information contained within the tweet, taking into consideration any formatting capabilities that may be available. The firm considers including the following benefit and risk information within the tweet:

NoFocus for mild to moderate memory loss; may cause seizures in patients with a seizure disorder www.nofocus.com/risk

And, as a further build:

… the firm should also communicate the brand and established names within the tweet. The firm considers including the following product information, together with benefit and risk information about NoFocus, within the tweet:

NoFocus (rememberine HCl) for mild to moderate memory loss-May cause seizures in patients with a seizure disorder www.nofocus.com/risk

As it turns out, the Tweet Summary takes up quite a bit of the available characters – and this is for a non-Black Box product. For those of you keeping count, it’s now up to 134 characters – leaving only six characters for Hi Mom.

Later on Pages 12-13 the agency spells out how verbiage and hyperlinks can be compliantly used for promotional speech such as sponsored Google links. Its well a well thought out and developed template. And it’s more restrictive – as it should be. After all, there are rules for advertising. Five years in the making. Headhurtz indeed!

Now let’s move on to a far more important public health issue: Correcting Independent Third-Party Misinformation About Prescription Drugs and Medical Devices.

For those of you not currently on NoFocus therapy, you will remember the 2009 Part 15 hearing on social media – the “SuperBowl of FDA Part 15 hearings.” One of the key questions the agency wanted to discuss was how to correct erroneous product information. All they got were blank stares and request for FDA guidance. Five years later – voila!

The agency writes:

This draft guidance is intended to describe FDA’s current thinking about how manufacturers, packers, and distributors (firms) of prescription human and animal drugs (drugs) and medical devices for human use (devices) should respond, if they choose to respond, to misinformation related to a firm’s own FDA-approved or -cleared products when that information is created or disseminated by independent third parties on the Internet or through social media or other technological venues (Internet/social media), regardless of whether that misinformation appears on a firm’s own forum or an independent third-party forum or website.

Key take-away is that the decision to correct errors is purely voluntary. (But, then again, technically so are all product recalls.) Where that becomes more complicated is how companies may choose to cherry-pick where they interceded for corrective purposes. This is not an issue addressed by the FDA in this draft guidance.  One thing this all means is more work for legal and regulatory review.

This draft guidance is all about user-generated content. The agency writes:

The Internet and Internet-based technologies have made it easier for third parties who are independent of firms to disseminate information about drugs and devices. Information created by third parties (which for purposes of this guidance is user-generated content (UGC)) might appear on an interactive portion of a firm controlled website or other interactive Internet/social media platform, or information might appear on a website or other Internet/social media platform that is independent of, or not under the control or influence of, a firm.

Many Internet/social media platforms allow for real-time and continuous communications and interactions (e.g., blogs, microblogs, social networks, online communities, and live podcasts) while other platforms do not provide a means for interactive content to be posted. Whether a forum is interactive may affect the means by which a firm is able to respond to information.

And, the agency stipulates, “UGC might not always be accurate and may be dangerous or harmful to the public health.” Well, yes. What’s a manufacturer to do?

Five years later, some helpful advice from the good people at White Oak.

Specifically:

If a firm voluntarily corrects misinformation in a truthful and non-misleading manner and as described in this draft guidance, FDA does not intend to object if the corrective information voluntarily provided by the firm does not satisfy otherwise applicable regulatory requirements regarding labeling or advertising, if any.

From a regulatory perspective, that’s a lot of wiggle room and should provide significant food for thought in erring on the side of more rather than fewer voluntary corrective actions.

But:

If a firm chooses to respond to misinformation about its products using non-truthful or misleading information or in a manner other than that recommended in this draft guidance, however, FDA may object if the information provided by the firm does not comply with applicable regulatory requirements related to labeling or advertising, if any.

Certainly. But what this also harkens back to is the agency’s previous guidance where it warns against using company-generated (sponsored) UGC relative to other companies’ products. That 12/11 guidance warns:

If a firm chooses to respond to public unsolicited requests for off-label information, the firm should respond only when the request pertains specifically to its own named product (and is not solely about a competitor's product).

Forewarned is Forearmed. Don’t get to cute.

This draft guidance isn’t about sponsored communications. The agency writes:

This draft guidance does not apply when a firm is responsible for the product communication that contains misinformation. A firm is responsible for communications that are owned, controlled, created, or influenced, or affirmatively adopted or endorsed, by, or on behalf of, the firm.

A firm is thus responsible for communications on the Internet and Internet-based platforms, such as social media, made by its employees or any agents acting on behalf of the firm to promote the firm’s product, and these communications must comply with any applicable regulatory requirements.

Specifically:

… this draft guidance applies when a firm is not responsible for a product-related communication that appears on the firm’s own forum, an independent third- party website, or through social media, and the firm chooses to correct misinformation about its own product contained in that communication. In such cases, we recommend that the firm do so as described in this draft guidance.

More detail is provided here relative to the nuance of “control” and “sponsorship (pages 7-8) and are worth reading.

Here are the agency’s eight ground-rules for “appropriate corrective information;”

* Be relevant and responsive to the misinformation;

* Be limited and tailored to the misinformation;

* Be non-promotional in nature, tone, and presentation;

* Be accurate;

* Be consistent with the FDA-required labeling for the product;

* Be supported by sufficient evidence, including substantial evidence, when appropriate, for prescription drugs;

* Either be posted in conjunction with the misinformation in the same area or forum (if posted directly to the forum by the firm), or should reference the misinformation and be intended to be posted in conjunction with the misinformation (if provided to the forum operator or author);

* Disclose that the person providing the corrective information is affiliated with the firm that manufactures, packs, or distributes the product.

Truthful. Accurate. Transparent. Three good rules of thumb. But what about “timeliness?” No advice from the agency on this one – but something crucial for manufacturers to consider since the goal here is to protect the public health.

Again, the agency offers important nuance on how to correct. For example, don’t just correct one mistake when multiples ones appear. The draft guidance also offers absolutely critical commentary relative to the depth and breadth of responsibility when correcting one piece non-sponsored UGC, “The firm is not expected to correct misinformation that appears on other webpages of the website.”

Those sweet sixteen words address a world regulatory angst.

Further:

Once a firm undertakes the correction of misinformation, FDA does not expect the firm to continue to monitor the website or communication that previously included UGC containing misinformation.

This does, however, point to the need for individual companies to develop their own policies in this regard. More work for legal/regulatory review teams!

And, for those of you who are thinking a little too hard, consider this important caveat:

… if a firm chooses to correct only misinformation that portrays its product in a negative light in a third-party communication but does not address misinformation that overstates the benefits of its product in that same clearly defined portion of the communication, the firm’s actions do not meet the recommendations in this draft guidance.

Voluntary corrective action isn’t just about “bad” information.

And, importantly:

FDA recognizes that a firm cannot control whether an independent third party refuses to correct the misinformation, or corrects only a portion of the misinformation even though the firm provided complete corrective information, or declines to include the respective required labeling, or declines to remove misinformation, or does not correct all the misinformation in one clearly defined part (if the firm sought to correct more than one piece of misinformation). Accordingly, FDA will not hold a firm accountable for an independent third party’s subsequent actions or lack thereof.

The perfect shall not impede the public good.

And, lastly:

FDA does not expect firms to submit corrections to the Agency when correcting misinformation pursuant to this draft guidance; however, FDA recommends that firms keep records to assist in responding to questions that may come from the Agency. The records should include, for example, the content of the misinformation, where it appeared, the date it appeared or was located, the corrective information that was provided, and the date the corrective information was provided.

Good guidance has been provided. Now it’s time for industry to do the right thing.

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US Health System: Most Valuable and Best Performing

06/17/2014 02:41 PM |

Every year the Commonwealth Fund comes out with a study ranking health care systems and every year the study claims to show that the US health system is, as the headline in Atlantic.com states: 

U.S. Healthcare: Most Expensive and Worst Performing
In a new international ranking, the United Kingdom ranks first, while the U.S. performs poorly across almost all health metrics.

This study -- or rather a version of it conducted by the World Health Organization --  has been thoroughly shredded by Scott Atlas in his Commentary article: The Worst Study Ever?  

As Atlas points out: "researchers divided aspects of health care into subjective categories and tailored the definitions to suit their political aims. They allowed fundamental flaws in methodology, large margins of error in data, and overt bias in data analysis, and then offered conclusions despite enormous gaps in the data they did have."

All to make the case for single payer health systems.  

In this case, the Commonwealth Fund measures everything except the quality of care.  It measures lots of process measures that are easily skewed by bias.  So for instance, in measuring "efficiency"  CW ranks countries based on percentage of GDP spent on health and percent of health care spent on administrative services.  Of course the US is destined to be the worst.

Next,  it ranks countries on access.  Again the US is trashed.   And the UK is number 1.   Don't laugh.  CW used "having access to basic medical care the same or next day."   Apparently wait times for cancer care, hip replacements, by-pass surgeries, etc. don't count.  Indeed,  CW ignores the explosion in outpatient same day surgery and walk-in clinics in the US.  

The US is also slammed for unfairness.  CW claims -- surprise! -- that the UK does the best on providing the same great care to everyone rich and poor.   Apparently, despite the exhaustive research CW did, the group failed to come across the Marmot report calling health inequality in the UK a ticking time bomb.   Here's the link in case CW wants to update it's study:  

Meanwhile,  CW ignores the following (courtesy of Scott Atlas again!):

"American cancer patients, both men and women, have superior survival rates for all major cancers.  Removing “lead-time bias,” where simply detecting cancer earlier might falsely demonstrate longer survival, death rates from prostate and breast cancer from the early 1980’s to 2005 declined much faster in the US than in the 15 other OECD nations studied (Australia, Austria, Canada, Finland, France, Germany, Greece, Italy, Japan, the Netherlands, Norway, Spain, Sweden, Switzerland, and UK)."

What about heart disease?

"A comparison of the US to ten Western European nations (Austria, Denmark, France, Germany, Greece, Italy, Netherlands, Spain, Sweden, and Switzerland) showed that 60.7 percent of Americans diagnosed with heart disease were actually receiving medication for it, while only 54.5 percent of Western Europeans were treated (a statistically significant difference)."

Also...

"Another comparison study showed that fewer Americans than UK residents die (per capita) from heart attack despite the far higher burden of risk factors in Americans for these fatal events. In fact, the heart disease mortality rate in England was 36 percent higher than that in the US. These superior outcomes from US medical care are particularly impressive, considering that American patients have far more risk factors (diabetes, obesity, chronic kidney disease) that worsen outcomes and death rates after heart attack and after heart surgery.

The US shows a far greater reduction in death rates from stroke, the third leading cause of death and the leading cause of disability in adults in the US and most Western European nations, than almost all Western European nations and the European Union overall."


So why did CW ignore outcomes like mortality and survival and focus on income inequality and how universal a health care system was.

You have to take into account CW's frame of reference.  If someone told you time again that the VA health system is a model of excellence, would you take their study on health care performance seriously? 

And boy does Commonwealth love the VA.

Here's CW president Stephen Shoenbaum gushing over the VA in an interview with Managed Care magazine: 

MC What parts of the health care system are working?

SCHOENBAUM: There are some examples of excellence within the U.S. health system. If we pick any given area, such as quality or driving down costs, we find examples of excellence. Some large systems are doing very interesting things. Kaiser Permanente and the Veterans Administration are managed systems that are trying to improve performance and reduce costs by using a primary care-based system and using information technology creatively. Another example is Geisinger Health System in Pennsylvania.

And here's a CW study of the VA, which it claims is a high performing health system.  I take that to mean it meets the standards CW set in the report dumping on US health care.  The study celebrates how the Memphis and Lincoln, Nebraska VA systems shortened wait times, reduced emergecny room vistis and reduced blood sugar levels in some patients.  

Hmm.. Memphis VA.. where have I heard that before..


VA Hospital Axed Veteran Programs While Approving $1 Million In Bonuses

The Memphis Veteran Administration (VA) Medical Center approved over $1 million in bonuses months before closing a therapeutic aquatic pool citing a lack of funds.

The Memphis VA Medical Center handed out $1,005,644 in bonuses for its approximately 2,000 employees in fiscal year 2010, according to data provided to The Daily Caller by Sandra Glover, the communications officer for Veteran Integrated Services Network (VISN) 9, which includes the Memphis VA Medical Center.."

And this:

Memphis Veterans Affairs Medical Center Flagged in Audit


The CW study is an exercise in confirmation bias, which is the " tendency to search for or interpret information in a way that confirms one's preconceptions, leading to statistical errors. Confirmation bias is a type of cognitive bias and represents an error of inductive inference toward confirmation of the hypothesis under study."

It was designed to reinforce the meme that goverment run health systems are better, fairer and cheaper.   This blog was a modest effort to speak truth to bias. 

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