With Supporters Like Those Accelerated Approval Doesn't Need Enemies

11/21/2011 08:45 PM |

There has been a lot of coverage about the Food and Drug Administration's decision to revoke approval for the use of Avastin in metastatic breast cancer.  Some commentators – who have at most a third hand understanding of the FDA’s handling of Avastin and how it squares or doesn’t with other cancer drugs granted accelerated approval – have lauded the withdrawal as good for innovation.  Most of it takes at face value FDA Commissioner's Hamburg 69 page decision in which she claims that the 'objective' evidence of benefit did not exist to support approval relative to the serious side effects of the drug. 

In particular, people who should know better let the FDA's spin affect their judgment.  For example, Avik Roy who writes for Forbes and is a fellow at The Manhattan Institute who in turn salutes another MI fellow for his support of the Avastin withdrawal:


"Paul Howard is the guy who gets it right:

        If you think (as I do) that the FDA should be expanding the accelerated approval pathway and allow more drugs to get to market based on promising         early studies. rather than waiting for large Phase III clinical trials that can take years to complete, you can argue that this outcome actually strengthens AA. Critics have charged that AA is sop to industry, and that companies never do the follow up studies to support AA. Avastin proves them wrong.

This is exactly the point. If you want the FDA to approve more innovative, new drugs based on promising but early clinical results, you have to give the FDA a way to revoke those approvals later on, should larger trials prove that those drugs aren't as safe or effective as they first seemed. This is why the FDA should be congratulated for the way it has handled the Avastin breast cancer saga, and why I hope we will see the FDA handle more cases like this one, not less."


http://www.medicalprogresstoday.com/2011/11/fda-did-the-right-thing-in-pulling-avastin-for-breast-cancer.php

Both of them have no clue.  

In fact the decision is less about Avastin and says more about the deep resistance at the Office of Oncology Drug Products to accelerated approval.  And those who support the reversal as some victory for medical innovation and accelerated approval do not understand either the scientific challenges of establishing clinical benefit in first line MBC care and, given how hard it is to demonstrate any clinical benefit in end stage patients, how significant the addition of Avastin to current therapies really is.   I am disappointed that observers treat the decision with the same sort of seat of the pants analysis reserved for Yankee post-game shows.

Dr. Hamburg's sympathy and support clearly lies with patients and the accelerated approval process.  However her explanation of the reason for the withdrawal of the approval reflects a combination of evasiveness and duplicity on the part of FDA staff in the Office of Cancer Drugs that has dogged the accelerated approval of Avastin from the start. 

Dr. Hamburg seeks to refute the claim that the FDA never switched the outcome measure of additional studies Genentech conducted to support ongoing approval of Avastin for MBC.   She claims (and I will guess this was written for her) that progression free survival (how long people lived without tumors growing) was always the standard and that the OODP did not demand to see an increase in overall survival  (how long people with and without Avastin treated before they died of any cause) which is a harder goal to meet.  In fact, her decision memo shows that the FDA never came straight out to say PFS of any given length would be the basis for approval.  Rather, FDA used the words "probably" or "might" and talks about the "potential" of using  PFS for approval as long as the "magnitude" of the benefit was significant given the risks of the drug.  Did FDA ever define what "magnitude" was sufficient?  Never.  Rather, as Dr. Padzur who runs OODP, told Genentech he would determine what the right "magnitude" would be when he saw the results. 

In otherwords FDA said that improvement in PFS is not adequate unless a large enough magnitude that it will decide after the fact and by the way if it doesn’t think it is big enough then a cancer drug must show a statistically significant improvement in OS to support approval.   And Dr. Hamburg calls this objective evidence? 

Additionally, Dr. Hamburg claims that the magnitude of clinical benefit has nothing to do with achieving a statistically significant benefit.  (Those words might and should be used by companies going forward as they design clinical trials.)  All well and good.  Yet the FDA ultimately revoked approval because Avastin did not show a statistically significant increase in overall median survival.   So does statistical significance  matter or not?  Apparently it does when you want to undercut approval for use of a product you opposed at the outset.  Similarly, when Dr. Hamburg claims that Genentech could never identify a subset of patients that might be more likely to benefit from Avastin in MBC she fails to point out that the FDA never asked for such data, nor did it state that it would extend approval based on response in a small group of patients.  In any event, the FDA decided that post-hoc analysis to identify super-response of a statistically significant amount is not evidence of magnitude.  

Her opinion ignores the fact that several other first line treatments for MBC were approved using PFS as an endpoint with half as much clinical benefit.   Let me put in terms that supporters of the decision can understand and let me put it in bold:  Specifically in the first-line treatment of MBC setting, two other drugs have received full approval using progression free survival or time to progression (TTP) effects of a much low magnitude than was used to grant Avastin accelerated approval.  Several second and third line drugs also were given full approval with well below the median gains in PFS of Avastin.  In all but two cases, full approval was granted without a statistical significant improvement in OS.


Dr. Hamburg offers some hints about how to show clinical benefit going forward: patient outcome data will count and designing trials to show which people might gain most from medicines will as well.  Her brief discussion about how groups that support continued use of Avastin in MBC could appear to biased because they receive unrestricted support from Genentech is a very low blow and hypocritical because the FDA is seeking to loosen its own conflict of interest rules to get more qualified experts on it's advisory committees. 

But in general Dr. Hamburg justifies the creation of higher threshold for the use of surrogate endpoints, a threshold that is arbitrary and without any empirical justification, in order to force all drugs to demonstrate OS.  All this suggests that allowing FDA to retain discretion over what is enough benefit will generate more uncertainty and ends accelerated approval as a real alternative.    The Avastin decision says less about the science of the FDA and more about how regulatory uncertainty (as a result of bias or lack of knowledge) can undermine innovation.   How can the so-called supporters of accelerated approval endorse Hamburg’s endorsement of this bait and switch?
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The Internationale

11/21/2011 08:45 AM |

I’ve just returned from the Third International Conference for Improving Use of Medicines (ICIUM).  The meeting was held in Antalya, Turkey – not that there was any Thanksgiving-related iconography.

The first thing to remember is that in the world of NGO healthcare policy, “international” means “non-Western.”

There were quite a lot of government officials from Africa, Asia, the Middle East, and a dusting of officials from the US (mostly USAID) and the EU.

The third ICIUM, for the first time, included members of the innovator pharmaceutical industry.  They were not asked to wear yellow stars. Noticeable by their absence were any generics manufacturers. 

Not surprisingly, most of the ICIUM participants fall into the category of old familiar faces, although there were some noticeable by their absence – like Jamie Love.  Well, absence makes the heart grow fonder.

It was an acronym-heavy event, with the most commonly used abbreviation being “RUM” for “Rational Use of Medicine.” (And remember, you can’t spell “rational” without R-A-T-I-O-N.) The other acronym of note was LMIC (“Lower/Middle Income Countries) also referred to as “indexed countries” (IC).

Every day brought a slew of interesting commentary.  For those of you unable to make the voyage, some selected tidbits:

Kathleen Anne Holloway (WHO) raised the issue of the deleterious impact of competition among NGOs (as well as the WHO) for project funding.  She was blunt about the negative consequences of “competition for prestige, attention, and priorities.” Those negative consequences, it turns out, result in less funding for some WHO projects.  Not that the majority of the audience gives marketplace competition any credence – although it’s surprising such incredulity also seems to extend to the marketplace of ideas.

Klaus Leisinger (Novartis Foundation for Sustainable Development) spoke about the need for everyone engaged in the international debate over the improved use of medicines to stop stereotyping each other.  (Amen. It’s about time we fought to put the “civil” back in “civil society.”) He then called for the creation of a “grand coalition” think tank to address the opportunities that working together might offer.  Klaus – sign me up.

Richard Laing (WHO), after praising GSK CEO Andrew Witty for his company’s devotion to corporate social responsibility, offered that “There is often an unfortunate disconnect between pharma HQs and their marketing departments when it comes to the issue of access to medicines.” Is a word to the wise sufficient?

(Remember -- A Word to the Wise was a 1770 play by the Irish writer Hugh Kelly. His first work was the 1767 hit False Delicacy.)

Dr. Laing also acknowledged the absence of both national and global generics companies from the ICIUM event -- a rather gaping hole that needs to be filled next time around. This issue came up again and again as panelists pointed out (again and again) that in many markets the prices of both branded and non-branded generics are actually higher than (off-patent) innovator medicines.

The role of generics cannot be overlooked considering that something on the order of 98-99% of all medicines on the WHO’s Essential Drug List were either never patented of their patents have long since expired in the IC countries. That being the case, there must be other reasons (beyond the traditional whipping boy of intellectual property rights) to explain why millions of people do not enjoy regular and reliable access to life-saving medicines.

Eva Ombaka (identified only as “formerly of the Tanzanian Ecumenical Pharmaceutical Network”) suggested that pharmaceutical companies should redirect their spending on “inappropriate marketing” to the public health dissemination of “access to medicine information.”

Note to Big Pharma – please refocus all “inappropriate marketing” line items to this effort.

Batool Jaffer Suleiman (Oman Ministry of Health) said that, when it comes to promoting RUM programs, government should “be seen as a support rather than the police.” Indeed.  But support for whom and for what? Price or patients? She also shared that her office publishes a regular RUM newsletter called “Pharmaco-Logical.” Who said Omanis don’t have a sense of humor?

Jing Sun (China National Health Development Research Center, Ministry of Health, China) offered an excellent presentation on her nation’s nascent healthcare reform efforts. Her complete presentation will shortly be available on the ICIUM website, http://www.inrud.org/ICIUM/ICIUM-2011.cfm.

She noted that China currently spends 5.14% of GDP on healthcare and (of that 5.14%) 44.5% is spent on pharmaceuticals (about 2.5% of total GDP). When you compare this to the roughly 17% of GDP spent on healthcare by most western nations (with roughly 12% directed towards medicines), there should be some questions asked. And the first one should be; is the higher Chinese percent spend on pharmaceuticals a good thing or a bad thing?

Time and again, speakers from the LMICs noted that their spending on pharmaceuticals was regularly in the 30-40 percent range of their annual healthcare expenditures (i.e., Jordan with 10% of GDP spent on healthcare and 34% of that amount on medicines).  Considering that product costs for index nations are significantly lower than western prices, perhaps the higher LMIC spend on pharmaceuticals is because medicines are something these nations can offer their populations – making up for a dearth of spending on the medical professionals and hospitals they do not have – but which represent the lion’s share of western healthcare spending.

In this respect, the high percentage of spending on modern medicines is akin to the LMIC telecom leap-frogging that has created a much higher penetration of mobile phones per capita than in the West. Something to think about.

Another question to ponder is to what extent government interventions may account for higher medicine prices in LMICs. Many governments implement aggressive protectionist policies that allow local generics companies to charge higher prices for products that are off patent – paying too much for older medicines that should be available to patients at commodity prices.

Saul Walker (Department for International Development, United Kingdom) bemoaned the unfortunate and counterproductive tension between “sustainability and innovation.” He also pointed out, with great honesty, that “government is not a unified entity” when it comes to developing and implementing healthcare policy.  (He was directing his comments at the LMICs – but it’s equally true across the board and around the globe.) He also mentioned “Big P and Small P” battles being fought both within governments and NGOs.  And the P (in case you haven’t guessed) stands for “politics.” Perhaps a panel at the next ICIUM can focus on a new definition of “P value for public health.”

(And, while we’re on the subject of ICIUM IV, there should be a subject track on safety. There was almost no discussion of bioequivalence, GMPs, narrow therapeutic indexing, therapeutic switching, or biosimilars.)

Jonathan Quick (Management Sciences for Health, USA) asked if universal health care was “the golden ring or a Trojan horse?”  His answer seemed to be “yes,” concluding that “failure to fully maximize needed expertise” is a major reason that universal healthcare systems are failing. One might also add “failure to understand the realities of market-based economies.” Socialism, as they say, works great until you run out of other people’s money. 

Maryam Bigdeli (WHO) made the excellent point that, “Many of today’s problems are because of yesterday’s solutions.” Or as Abraham Lincoln said, “You cannot escape the responsibility of tomorrow by evading it today.”

Danya Qato (Brown University), offering one of the few US-centric presentations, made the excellent point that when it comes to medicines (specifically) and healthcare (more broadly) the barrier isn’t just cost. (Shocking, right?) Her US-based research among a largely Medicare-eligible population demonstrates that racial, social, and geographic disparities play a major role and that “access does not equate to use.” Reality.  What a concept.

The other US-based presentation was by Elissa Ladd (MGH Institute of Health Professions). Her talk was on the detailing practices of Big Pharma towards the growing population of nurse-prescribers. (According to Ms. Ladd, there are 150,000 nurse-prescribers in the US, compared with only 100,000 physicians in general practice.)  You’ve heard the argument before – pharmaceutical detailing is “bad” because it helps to “sell” products for profit! 

She provided no evidence (anecdotal or otherwise) that the information pharmaceutical detailers provide to nurse-prescribers is in any way slanted or anything other than factual and 100% FDA-compliant. Her organization undertook some “educational” efforts that resulted in nurse-prescribers questioning the reliability of pharma-provided information.  She positioned this as “success.” But – is having nurse-prescribers (or, for that matter, any prescriber) discount important medical information really a move in the right direction?

And then there’s the Access to Medicine Index (ATMi). The ATMi is an attempt to measure and compare the corporate social responsibility of both innovator (20) and generics (7) companies based on a number of different (and often quixotic) indicators. According the Access to Medicine Foundation, the index “aims to help poor people in developing countries gain access to medicine by encouraging the pharmaceutical industry to improve its commitments and practices related to this issue.” Since it’s a comparison, the theory is that competition amongst companies will drive desirous “socially responsible” behaviors.

A noble goal – but the devil is in the details. Consider subjectivity.  For example (and most notably) the index’s four strategic pillars are “commitments, transparency, performance, and innovation.”  And its “technical” benchmarks include such vague categories as General Access to Medicines Management, Public Policy and Market Influence, and Capability Advancement in Product Development and Distribution.

As Goran Tomson (Karolinska Institute) pointed out, the index’s methodology cannot be reproduced, hence it cannot be considered statistically valid -- unless you choose to abide the Marxist (Karl not Groucho) maxim that “a special environment creates a special class.”

There are also troubling issues relative to the ATMi’s metrics for success.  As the index’s methodological designer, Afshin Mehrpouya (HEC, Paris), opined, the only current measurements are “web hits and media coverage.” Not very exciting, plausible, or helpful from a health policy analysis perspective.

Another ATMi metric is the opinion of patient groups.  When asked why certain patient groups were chosen (they are not named in the ATMi), the answer was that groups were chosen based on their “credibility.” In NGO-land that’s code for groups who do not accept funding from the pharmaceutical industry or may not share the anti-private sector bias of the party line.  At minimum, that’s a dubious selection bias.

Most damning was Dr, Mehrpouya’s admission that the index, “doesn’t take the patient viewpoint into perspective.

Dr. Tomson also pointed out that the ATMi’s “review committee” consisted almost entirely of “familiar faces,” thus creating an issue of normative bias.

These are all polite ways of saying that the design criterion stacks the deck. But, hey – doesn’t the end justify the means?

What the ATMi has succeeded in doing is getting the attention of innovator companies who want to strut their corporate social responsibility stuff index-wise. The result is that many LMICs are considering the index when making national formulary decisions, thus giving additional points to innovators over generics companies.  Some observers at the ICIUM conference viewed this as an unintended negative consequence. But the truth hurts.

To paraphrase Adlai Stevenson, “If NGOs and generics companies will stop telling lies about pharmaceutical innovators, perhaps Big Pharma will stop telling the truth about them.”

One suggestion that came up during the panel debate on the ATMi is to create a parallel index that measures LMICs by whether or not their policies and political environment facilitate or hinder their citizens’ access to healthcare. One such measure, as bravely noted by Jeffrey Kemprecos (Merck), is to measure and address the 800-pound gorilla in the room – the lack of transparency in the public sector and – yes, he dared utter the word -- corruption.

Goran Tomson put the discussion about the ATMi -- as well as the entire ICIUM enterprise -- into perspective when he said the index lacked for “higher ambitions.”

Any maybe that’s the best go-forward message from and for ICIUM – let us strive for “higher ambitions” as colleagues who can (in the words of Klaus Leisinger) “agree to disagree.” Easier said than done.  But it’s worth a try.

In other words – let’s talk turkey.

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Crime and Punishment

11/21/2011 08:42 AM |

During my tenure at the FDA I served on the agency’s first Counterfeit Drugs Taskforce. Alas, one of the items in our draft report – that criminal penalties for counterfeiting be significantly enhanced – didn’t make it into the final recommendations since it was seen as exceeding the agency’s mandate (and stepping on toes at the Department of Justice).

Well – better late than never.  A new bipartisan (and bicameral) effort has been introduced to stiffen the penalties counterfeiters will face for putting illegal and unsafe medicines into the medicine chest of unsuspecting Americans.

The Counterfeit Drug Penalty Enhancement Act will increase penalties for the trafficking of counterfeit drugs to reflect the severity of the crime and the harm to the public. While it is currently illegal to introduce counterfeit drugs into interstate commerce, the penalties are no different than those for the trafficking of other products, such as electronics or clothing. The Counterfeit Drug Penalty Enhancement Act will target violators that knowingly manufacture, sell or traffic counterfeit medicines to the USA.

On the Senate side the bill is sponsored by, Patrick Leahy (D, VT), Chuck Grassley (R, IA), Michael Bennet (D, CO), and Richard Blumenthal (D, CT) and on the House side by Patrick Meehan (R, PA) and Linda Sanchez (D, CA).

Senator Leahy: “While the manufacture and sale of any counterfeit product is a serious crime, counterfeit medication poses a grave danger to public health that warrants a harsher punishment. This legislation will raise those penalties to a level that meets the severity of the offense.  Deterring this epidemic problem is a bipartisan effort.”

Senator Grassley: “Counterfeit medicines are some of the most profitable commodities for criminal organizations.  Purchases of counterfeit drugs by unsuspecting customers are growing at alarming rates, especially over the internet.” These drugs present a serious threat to the health and safety of people around the world. It’s important we address this threat by imposing harsher penalties on criminals who counterfeit these medicines.”

It’s about time.

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Seize the Dais

11/19/2011 08:41 AM |

Alas Avastin.

Rather than rehashing the debate, let’s just say (1) this decision wasn’t a surprise and (2) it’s a missed opportunity for advancing regulatory science.

Regardless of where you stand on Avastin for HER2-negative metastatic breast cancer – this was a “teaching moment” for the FDA. And the agency missed it.

Specifically, it was an opportunity for the FDA to talk about the future of molecular diagnostics and how it wants to be a partner with industry in their development. Peggy & Co. should have taken the opportunity to go beyond communicating a specific regulatory decision and seized a leadership position on a crucial healthcare policy issue. This is even more disappointing considering the high profile the agency has given recently (and appropriately so) to its Advancing Regulatory Science Initiative (ARSI).

Alas not.

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CMPI Capitol Hill event: "PDUFA without the Politics"

11/17/2011 12:06 PM |

PDUFA without the Politics

When politics trumps the public health bad things happen. The current conversation surrounding the reauthorization of the Prescription Drug User Fee Act (PDUFA) must focus on (among other things) the First Principle of Predictability as well as ensuring that the FDA can fulfill its role as an important ally in advancing healthcare in America.

Please join the Center for Medicine in the Public Interest (www.cmpi.org) and some of the nation’s top experts in PDUFA and FDA reform for an interactive panel discussion of “Defining the Future of the FDA: PDUFA V and Beyond.”
 
RSVP to Mario Coluccio:  mcoluccio@cmpi.org

DELI LUNCH TO BE SERVED

DATE: Tuesday, November 29th
TIME:  12:00 – 1:30PM
LOCATION: RM. 2168 (Gold Room) Rayburn House Office Building
 
Peter J. Pitts (Moderator), Former FDA Associate Commissioner, President of the Center for Medicine in the Public Interest

The Honorable Michael C. Burgess, M.D., Vice-Chairman, Subcommittee on Health, U.S. House of Representatives

Vincent J. Ventimiglia, Jr, Former Assistant Secretary for Legislation at the US Department of Health and Human Services, Senior Vice President in the Health and Life Sciences Practice at B&D Consulting, a division of Baker & Daniels LLP.

Paul T. Kim, Former Deputy Staff Director for health policy for Senator Edward M. Kennedy, Partner at Foley Hoag LLP in the Government Strategies practice.

Michele J. Orza, Former Assistant Director of the Health Care Team at the Government Accountability Office, Principal Policy Analyst at the National Health Policy Forum.

Tim Franson, Former Vice President, Global Regulatory Affairs, Eli Lilly & Co., President, USP Convention, Senior Vice President, Health and Life Sciences Sector, B&D Consulting.

RSVP to Mario Coluccio:  mcoluccio@cmpi.org
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The Quote of the Week

11/17/2011 12:02 PM |

“It is truly astounding that Michele Bachmann would continue on this road despite science contradicting her. Never mind the fact that in Minnesota, including the district she represents, there was just a measles outbreak that was attributed to a fear of vaccines brought on by statements like the ones Ms. Bachmann has made. It is sad to see that Congresswoman Bachmann values getting media appearances more than the health and safety of children.”
 
- GRASP spokesman Evan Siegfried
 
This was in response to the Congresswoman’s comment about Gardasil earlier this week in Iowa, where she told a parent that her daughter shouldn’t “have to live with the ravages of this vaccine.”
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Should Consumers Be Forced To Switch Meds When They Go Generic?

11/15/2011 11:06 AM |

Apparently the NYT's Duff Wilson thinks so: 

Plan Would Delay Sales of Generic for Lipitor
By DUFF WILSON

"The biggest introduction of a generic drug in pharmaceutical history is being met with tough business strategies by Pfizer and pharmacy benefit companies, according to recent letters to pharmacists.

Many drugstores are being asked to block prescriptions for a generic version of Pfizer’s Lipitor starting Dec. 1, when the company loses its patent for the blockbuster cholesterol drug and generic competition begins.

Medco Health Solutions, among the nation’s largest pharmacy benefit managers, is one of the companies issuing instructions, seeking to have pharmacists keep filling prescriptions with the more expensive Lipitor for six months."

http://www.nytimes.com/2011/11/12/health/plan-would-delay-sales-of-generic-for-lipitor.html?_r=2

Except that it won't be more expensive to consumers...

"Pfizer has agreed to large discounts for benefit managers that block the use of generic versions of Lipitor, according to a letter from Catalyst Rx, a benefit manager for 18 million people in the United States. The letters have not previously been made public.

A pharmacy group and an independent expert say the tactic will benefit Pfizer and benefit managers at the expense of employers and taxpayers, who may end up paying more than they should for the drug.

Pharmacy benefit managers are middlemen between drug companies (the sellers) and insurers and employers that sponsor insurance plans (the buyers). "

Let's presume Wilson's unsupported assertion that employers and taxpayers will pay more is correct even though it isn't since PBMs benefit whether the price drops due to discounts or generic drug introduction.  Should patients who are on Lipitor be forced to instantly switch to a generic version?  Did Duff consider the impact of drug switching to save money in the short term on the ability to reach optimal lipid levels?

No.  And he should have.  An across the board switch can and does affect compliance.  And in the short term at least a percentage of patients (of all ages) saw their bad cholesterol levels increase.   Switching from high-efficacy lipid-lowering therapies to simvastatin and low-density lipoprotein cholesterol goal attainment in coronary heart disease/coronary heart disease-equivalent patients. Tunceli K, Sajjan SG, Ramey DR, Neff DR, Tershakovec AM, Hu XH, Tomassini JE, Foody JM. J Clin Lipidol. 2010 Nov-Dec;4(6):491-500

How many strokes and heart attacks occured as a result?  Duff doesn't care.

I am not making a case against using generic drugs or even switching.  Rather, I am asking why the NY Times and every other major media outlet never considers the impact on price-driven changes on the total health or cost of care.  Switching has to be done carefully and has to be explained to patients that equivalent generic drugs are generally as safe and as effective as the innovator product.  So a six month transition process, paid for by Pfizer and PBMs is not sticking it the taxpayer.  It could be smart and patient-centered medicine.

Does Duff understand that?





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The Supremes To Hear Obamacare Case

11/14/2011 02:13 PM |

The Supreme Court will hear arguments regarding whether the individual mandate under Obamacare is constitutional.  Last week I observed in roundabout fashion that while the Court is keenly interested in cases that affect congressional power under the Commerce Clause, the default position of almost every Court seems to be that decisions about how that power should be exercised ought to be left to Congress and ultimately up to the voters.  The Court is -- with rare exception -- always careful to follow a fairly well-established test to determined whether a law should be voided or remain in place.  

In the case of the Commerce Clause and whether the government can compel people to purchase health insurance the Court is, following the reasoning of Judge Silberman, The Court will look at " four factors in determining whether legislation represents a valid effort to use the Commerce Clause power to regulate activities that substantially affect interstate commerce.  I am paraphrasing from the Supreme Court decision to invalidate the Gun-Free School Zones Act of 1990 on the grounds is exceeded the authority of Congress to regulate under the Commerce Clause:

   Whether the activity was non-economic as opposed to economic activity; previous cases involved economic activity.
    Whether the purchase of insurance is an interstate commerce activity
    Whether there had been Congressional findings of an economic link between not purchasing insurance, the economy and/health care costs at any point in   time
    Whether there is a link between regulated activity or inactivity and interstate commerce.   http://en.wikipedia.org/wiki/United_States_v._Lopez

The third factor is the one that Silberman focused on.  And like other judges who did so they bought the argument that without a mandate people who didn't have insurance would add costs to the system at some point and therefore not buying coverage is, broadly defined, an economy activity.  However, one aspect of the Lopez case not always considered in current discussions.   The Court of Appeals that ruled  the Gun Free Act unconstitutional found the findings and evidence presented before Congress to justify the passage of the Act pursuant to the federal Commerce Clause power was simply insufficient to uphold the Act.  http://en.wikipedia.org/wiki/United_States_v._Lopez#cite_note-9

I don't know if the states bringing suit against the federal government have raised or will raise this argument.  I don't know if doing so is a plausible legal strategy.  But it would seem pretty easy to poke holes in the claim that the lack of a mandate is responsible for rising health care costs and to argue that the findings and evidence presented by Congress are not enough to support the health care law.  

It's probably a point worth pursuing for the following reason:  I still believe that whatever the Court decides it won't be to the advantage of the proponents of the law and President Obama in particular.   If the Court overturns the mandate the administration has made it clear that the rest of the expansion of government power can go on, as well it can.   And if the Court upholds the law, it will re-ignite resentment and then some.  Whatever happens, Obamacare will become an important campaign issue, as will it's repeal or wholesale revision.  That is as it should be. 

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US Supreme Court to hear legal challenges to the health care law

11/14/2011 01:26 PM |

From the pages of National Journal:

The Supreme Court said on Monday it would consider the challenge to last year's health care reform law, setting up a major ruling on the Obama administration's signature legislative achievement just months before the presidential election.

The case is likely to be heard in March, meaning that a final decision is likely at the end of the Court’s term, in June.

Apparently in recognition of the complexity of the issues presented by the cases, the Court has asked for an unusual amount of time for oral arguments. The order said the court would listen to five and a half hours of arguments—a rare departure from its usual practice of allocating an hour to hear a case.

The Court has asked lawyers to answer four legal questions about the law in their briefs, signaling that it will issue rulings on each of them.

Read more here.

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TREAT or Trick?

11/12/2011 08:51 AM |

The Transforming the Regulatory Environment to Accelerate Access to Treatments (TREAT) proposed by Senator Kay Hagen (D,NC) would create two new FDA approval pathways. Drugs would be eligible for "progressive" or "exceptional" approval if they provide meaningful advances in the treatment of an unmet serious or life threatening condition. FDA could also approve drugs based on approval in the EU as well as in Australia, Canada and some other countries.

TREAT would permit progressive approval based on data "reasonably likely" to predict clinical benefit, the standard currently used for accelerated approval. Unlike accelerated approval, drugs could receive progressive approval without data from a surrogate endpoint. Exceptional approval could be granted when the data necessary to satisfy the standard for approval "cannot ethically, feasibly or practicably be generated." would also relax conflict of interest restrictions for advisory committee members, create a fixed term for the FDA commissioner, and revise FDA's mission statement to emphasize the promotion of biomedical innovation.

The draft bill can be found here.

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Just To Live Is Holy

11/11/2011 10:13 AM |

Everyone should read Diana Furchtgott-Roth's elegant and moving tribute to her friend David Salzman who lost his battle with bile duct cancer last Saturday...

http://washingtonexaminer.com/opinion/columnists/2011/11/david-salzmans-valiant-fight-what-truly-matters

David Salzman's valiant fight for what truly matters
By: Diana Furchtgott-Roth | 11/10/11 8:05 PM
It was December 2006, just before Christmas, when my friend David Salzman called. "I have bile duct cancer, and they've given me only three months to live."

That was almost five years ago. At 1 am on Saturday morning, David, age 53, a Maryland entrepreneur, succumbed to an infection, dying at Johns Hopkins Hospital in Baltimore, with his mother, Nancy Salzman, next to him.

He was one of the longest-surviving patients with bile duct cancer. As well as his mother, he leaves his wife, Beth Kevles; two children, Michael, 16, and Joel, 14; and his brothers, Andy and Jimmy.

For David, our health insurance system worked. As an entrepreneur, he had small-business insurance through Blue Cross Blue Shield. It didn't drop him and never questioned his care. David had only praise for Blue Cross.

I met David in Washington, D.C., in 1986. With two degrees in physics, a B.S. from Yale and a Ph.D, from the University of Chicago, he could have taken the usual academic route. Instead, he founded startups to develop new products.

One of his first companies was Polychip, where he pioneered proximity chip-to-chip communication, which dramatically increases the data rate between chips by stacking them on top of each other.

David sold that patent to Sun Microsystems, later bought by Oracle, which now has a government contract using the technology to develop a new generation of supercomputers.

Another of his companies, LightSpin Technologies, uses new ways to manipulate, detect, and generate light. When David died, he was developing ways to use light waves to find land mines. He considered this vital because of the danger posed by hidden mines.

One of his partners, Eric Harmon, told me, "You shake the ground with a loud noise, and then use the pattern of the sound waves to find the land mines."

Right until his death, David was active in community meetings about the new Montgomery County rail line, the Purple Line. He was intensely concerned with the way politics were overcoming science, and showed how studies justifying the project were artificially inflating ridership and energy savings and minimizing the noise levels.

David was more than just a scientist, he was a modern Renaissance man, able to enjoy literature, opera, and politics with equal knowledge and gusto. That's why my husband and I asked him to be the godfather to our third son, Godfrey, hoping a little magic would rub off.

"There wasn't anything that could be learned that David didn't want to learn," his mother told me on Wednesday.

This extended to his cancer treatments. David's college buddy, Phil Schiff, organized a team of friends to drive David to Hopkins for his weekly treatments so that Beth could spend more time with the boys. I was honored to be on the team.

At the hospital, David would go over the printouts of the blood tests, questioning the nurses and technicians. He chose the most aggressive treatments possible, overcoming pain and side effects, anything to have more time with his family.

Thoughts of his family spurred him on. David kept going by trying to survive until specific events such as Michael's bar mitzvah, Joel's bar mitzvah, and then, the final goal, Michael's 16th birthday on Sept. 23.

Beth told me on Thursday, "David did not want to be remembered for his cancer. Cancer was what he had, not what he was." On the drives to Hopkins we'd talk not about cancer treatments, but about how our various children were doing in school and what they would do over the summer.

Because, in the end, that's what matters.

  Read More & Comment...

Group Think

11/11/2011 08:59 AM |

The Digital Health Council (DHC) was created to serve as the collective public voice and provide a national public forum for the discussion of current and future issues relevant to digital and electronic marketing of healthcare products and services. I am honored to serve on the Council’s advisory board.

On October 13, 2011 at the Marketing to the Digital Consumer conference in Fairfield, NJ (hosted by DTC Perspectives), I participated on a panel with some of my fellow DHC advisory board members. My fellow panelists were:

Mark Bard, Co-founder of the Digital Health Coalition

Joan Mikardos, Senior Director, Digital Center of Excellence, Sanofi

Jeremy Shane, President and Chief Operating Officer, HealthCentral

Jay Goldman, VP Strategy, Klick  

Gautam Gulati, Chief Medical Officer, Physicians Interactive Holdings

My opening comments commenced as follows:

In my opinion, social media must be viewed primarily as a way to advance public education, public health, adherence, compliance – all the things we say are really important – but always come second to selling product. We’re not going to advance the use of social media as long as we’re stuck in “sell” mode.  When we move towards advancing the public health we begin to revive the mission of the pharmaceutical industry.

A transcribed version of the panel discussion has been created as a white paper and can be found here. No punches were pulled.

  Read More & Comment...

Circuit Court Decision and the Individual Mandate

11/11/2011 12:02 AM |

Those hoping for a legal shortcut to overturning Obamacare could be disappointed.  While some jurists are concerned about giving Congress too much power absent a compelling need others are focused on insuring that Congress has maximum latitude to legislate, even if the laws it enacts are bad ones, produce unintended consequences or upset large segments of the population.   In the case of Obamacare, opponents of the law may have focused too  much on the individual mandate because that was the only aspect of the law that could be challenged from a constitutional standpoint.  There are many other elements of the law worth despising in addition to how it was rammed through.  Ironically, a court 'victory' for Obamacare could trigger a greater voter backlash against the law in the 2012 elections.  That could lead to Obamacare being struck down and replaced with something more sensible through the legislative process.  Which is how the Founders sort of saw things from the outset.   Read More & Comment...

Jobs destroyer

11/10/2011 01:27 PM |

Politico reports that the NFIB has released a new study showing significant job losses on account of the tax imposed on health plans:
 
The National Federation of Independent Business is announcing a new report this morning that says the health insurance premium tax (levied on insurance plans) will cut as many as 249,000 jobs in the private sector by 2021 and cause a loss of $18 billion to $30 billion in sales. The drop would be a result of rising premium costs for employers and consumers. Just last week America's Health Insurance Plans released a similar report that said the tax would increase premiums by as much as 3.7 percent. The White House pushed back on the AHIP report and said it ignored "provisions that will increase transparency and bring costs down."
 
Read the NFIB report here.
  Read More & Comment...

Kansas gets innovative on Medicaid

11/10/2011 01:21 PM |

Kaiser Health News reports on Kansas Governor Sam Brownback’s plan to put the state’s Medicaid patients into privately mange-care plans:

Kansas Gov. Sam Brownback announced a major overhaul of the state’s Medicaid program today, which would put nearly all Medicaid recipients into private, managed-care plans.  While low-income families are currently in such plans, elderly and disabled Kansans receive care through a fee-for-service system. 

The state has drafted a request for proposals from private contractors willing to provide comprehensive health, mental health and long-term health care services at a fixed rate per person.  State officials say they expect to select three vendors, who will compete for clients.  

At a news conference today, Lt. Gov. Jeff Colyer, a physician and the administration’s point man on the Medicaid reform effort, predicted the changes could slow the growth in Medicaid spending by nearly one percent a year. That would save the state more than $350 million over the next five years and would save the federal government $500 million at the same time.

Read the full story here.  Read More & Comment...

The Inside Story

11/09/2011 08:20 AM |

A new report in the Chicago Sun-Times raises an important question in the looming debate over generic interchangeability – the non-active ingredients in pharmaceuticals.

Just as there are bioeqivalance issues between innovator and generics – so too are there important differences between generics of the same molecule.  And an important issue in both cases is the variety of fillers, colors and additives in these products that have nothing to do with the reason it is prescribed but can have unintended and undiagnosed consequences that can range from stomach pains to headaches to hyperactivity.

“It’s frequently overlooked by medical professionals and patients because, when we prescribe medication, we’re prescribing the active ingredient,” said Dr. John Saran, who specializes in internal medicine with Edward Medical Group. “(But) there may be 15 other things in there.”

While patients generally are asked if they have allergies to any medications, the allergy refers to the drug, not necessarily the fillers in it.

For instance, lactose is a common filler in pills and capsules. If a patient is lactose intolerant, the patient might believe they cannot tolerate the drug, when in fact, it is the filler that is causing cramping. Neither the doctor nor the patient may be aware that the pill contained lactose because, according to Saran, many times the additives and filler information are not included on the handout from the pharmacy.

According to the Sun-Times report, “Common additives … can lead to asthma attacks, anaphylaxis, runny nose and adversely affect children with learning disorders. Artificial sweeteners can affect those who have hyperactivity. Vegans may not want capsules because they are gelatin based. Even dye-free versions of medicine may still contain preservatives that can cause reactions. Children’s medications are especially a problem because they are flavored and colored to make them more palatable."

As if adverse event reporting wasn’t tough enough already.

  Read More & Comment...

And don't call me chief!

11/08/2011 07:32 AM |

According to BioCentury, Lisa Barclay has replaced Molly Muldoon as chief of staff for Commissioner Margaret Hamburg. Barclay, a partner at the law firm of Zuckerman Spaeder, worked at FDA in the 1990s in the Commissioner's Office of Policy.

  Read More & Comment...

Peekaboo -- ETASU

11/07/2011 09:33 AM |

The 4^th Annual Risk Management and Drug Safety Summit is over.  But the reverberations will be felt for some time to come.

After event chair (me) opened with a challenge for industry and regulators to step up to the challenge of “the responsibility of risk, the esteemed presenters were, to put it mildly – feisty.

(My complete opening comments on the “responsibility of risk” can be found here and many of the presentations from the Summit can be found here.)

The first keynote presenter at the summit was Janet Woodcock, who said that “advancing the science of safety is a shared effort.” She also shared the agency’s relief (shared by the majority of summiteers) that MedGuides shall now exist outside of a REMS context.

When MedGuides were in safety’s land.  Let my REMS plans go.

Janet also made it clear that the outcomes data bases now available to the agency’s Sentinel program will not be used for comparative effectiveness purposes.

She then addressed the issue (also part of the PDUVA V discussion) or a benefit/risk assessment tool.  Specifically, Janet laid out five “key considerations”: (1) analysis of condition, (2) unmet medical need, (3) clinical benefit, (4) risk and (5) risk management. 

Sounds like a plan.  Well – almost.

Dr. Woodcock then discussed a pilot program that most in the room (myself included) had never heard of before.  Janet shared that CDER has begun a pilot program (with six unnamed NMEs) wherein the various sectors of review teams will fill out their own benefit/risk assessments (based on the five criteria mentioned above) to explain how they arrived at their relative positions. She didn’t mention whether or not these findings would be made public. 

(Did somebody say, “transparency?”)

Janet also talked about the agency’s continuing and crucial struggle to advance PMI (patient medical information).  The goal of CDER’s current initiative to create a one-pager for Rx products more akin to the Nutrition Facts Panel (aka, “the food label”) or an OTC “drug facts” box.

A noble effort – but the devil is certainly in the details.  For example – would this document be progressive, or would existing products need to create them as well.  If progressive, would this single sheet be part of the initial label negotiation process? And if retroactive – can the agency use its FDAAA directive labeling authority to create the page itself -- and, if so, based on what social science? Where would the boundaries be between product education and promotion? How would this document be distributed (hard copy, websites, social media, etc.)? Would generics use the same information and, if so, what about narrow therapeutic index products? Janet didn’t have all of the answers – but it’s certainly a provocative topic worth pursuing.

Next up was Sir Alasdair Breckenridge (Chairman, MHRA), who turned heads by saying that, “We need to stop talking about safety.  Safety should be removed from our lexicon.  We must focus on benefits and harms.”

Sir Alasdair also discussed the difficulties of regulating in an environment where EU- level directives add additional burdens to national level regulatory authority.  Specifically, he shared that mandarins in Brussels have altered the definition of “adverse reaction.”  The new definition includes:

“… noxious and unintended effects resulting not only from the authorized use of a medicinal product at normal doses, but also from medication errors and uses outside the terms of the marketing authorization, including misuse and abuse of the medicinal product.”

How, Sir Alasdair, asked, can any agency address adverse reactions based on medical errors and product abuse?  Are they signals or noise?

Brussels sprouts.  Alasdair doubts.

He also cited an interesting study (Golder, S., et al, PLoS Medicine, May 2011) on the issue of adverse effects data derived from RCTs as compared to observational studies.  The conclusion of this paper is that:

“Empirical evidence indicates that there is no difference, on average, in the risk estimate of adverse effects of an intervention derived from meta-analyses of RCTs and meta-analyses of observational studies.  This suggests that systemic reviews of adverse effects should not be restricted to specific study types.”

This opens up a big can of worms relative to the considered value of observation studies.  But, as Alexandre Dumas said, “All generalizations are dangerous – even this one.”

Picking up on Sir Alasdair’s point about “benefits and harms,” Dr. Tim Franson (former regulatory chief at Eli Lilly & Co, current President of the USP Convention and an SVP at B&D Consulting) asked a smart question, should we be talking about risk at all – or about benefit risk? shared a timely quote from Edward Tenner’s treatise, Why Things Bite Back: Technology and the Revenge of Unintended Consequences, “Any technology powerful enough to improve life radically is also capable of abuse and prone to serious unanticipated side effects.  Mix new technologies with the wide variations in how organizations and individuals behave and you often have a recipe for explosion.”

That passage deals with nuclear power.  Discuss.

Dr. Franson concluded his remarks reminding the audience that, when it comes to global benefit/risk management, “We all share in the responsibility.”

Day Two of the summit featured a keynote address by John Lechleiter, Chairman, President and CEO of Eli Lilly and Co. who commented:

“We’d like to see the FDA adopt systematic, transparent Benefit/Risk assessment methods consistently across review divisions and the Office of Surveillance and Epidemiology.  This would support more balanced regulatory decision-making … and enable the Agency to clearly communicate the rationale for its decisions to industry, providers and the public at large.  I note here FDA’s support for medication adherence in 2011 – which we applaud.  But a more balanced approach to communicating both the benefits and risks of a drug would also aid in the effort to improve adherence.

FDA should accelerate efforts to adopt and apply the best scientific methods and also incorporate the perspectives of affected patients – which can form the basis of consistent, transparent, reproducible decision-making. 

Here are some things that I believe FDA could do right now to accelerate the benefit-risk agreement outlined in PDUFA:

Identify external benefit-risk experts as key consultants.  FDA has acknowledged the need for systematic benefit-risk assessment tools … and has engaged external experts sporadically over the past several years.  To accelerate progress, FDA should identify and pull together the leading academicians, clinicians, and thought leaders in the field now to augment their internal practical experiences in drug review.

Engage other major regulators in this effort.  For example, FDA could advance discussions with EMA and other agencies to develop a harmonized approach to benefit risk assessment that would enrich decision-making and enable effective communications.  This is important, as there’s potential for discord as regulators globally develop different tools and approaches.  Adopting globally harmonized assessment of benefits and risk could alleviate regulatory confusion and uncertainty and help advance the public health.”

(John’s compete remarks can be found here.)

The theme of shared responsibility ran through the entire event.  But talk is cheap. And if we all believe that to be true – then it must also instruct our rhetoric.  For example – should ETASU (Elements to Assure Safe Use) be changed to ETASU (Elements to Assist Safe Use)?  After all, (and to brutally frank here) nothing can ever assure safe use, but if we all assist in the endeavor, well, there’s a much higher chance for success.

Shared responsibility. If you can’t say it, you can’t do it.

Which brings us back to where we started – risk as a shared responsibility facilitated relationships built on trust.  Trust between regulator and regulated.  Trust between physician and patient.  Trust enhances perception and, as the saying goes, perception is reality.

  Read More & Comment...

Look for the Union Label

11/04/2011 07:16 AM |

Generally, when you think about President Obama’s  “core constituencies,” blue-collar unions are at or near the top of the list.

Consider, then, the following groups and their united position against the President’s plan to impose additional mandatory rebates on the pharmaceutical industry:

(And let’s call it what it is – a tax.  More precisely, an excise tax imposed by Uncle Sam on drug sales – and not a single penny goes towards lower costs for a single patient.  Not one. The cash goes into the general fund.)

·      The International Brotherhood of Electrical Workers

·      The International Brotherhood of Boilermakers

·      The International Association of Police Associations

·      Sheet Metal Workers’ International Association

·      International Association of Fire Fighters

·      International Association of Bridge, Structural, Ornamental, and Reinforcing Iron Workers

And the soliDarity is for a good reason – according to a new study by the Battelle Technology Partnership Practice, the President’s new tax on Medicare Part D would:

·      Increase Medicare prescription drug premiums by up to 40%

·      Increase annual out-of-pocket spending for almost 18 million seniors by as much as $208 annually

·      Increase yearly total out-of-pocket drug costs for seniors by up to $3.7 billion.

The bottom line is the bottom line: As Yale Economist Fiona Scott Morton plainly states, “Applying the Medicaid rebate rule to Medicare Part D would likely result in higher prices for consumers in the private sector.”

That is not what the union movement signed on for when they supported the passage of the Affordable Care Act.

But wait, it gets worse.

The President’s tax a job killer.  According to the Battelle Report, the tax could cause the elimination of between 130,000 and 260,000 jobs – many of them in the construction industry -- and hence the union revolt.

And, to add insult to injury, the President’s tax would also stifle life science innovation.

It’s hugely disappointing that the same man who (as a United States Senator) once said that …

“Realizing the promise of personalized medicine will require continued federal leadership and agency collaboration; expansion and acceleration of genomics research; a capable genomics workforce; incentives to encourage development of genomic tests and therapies; and greater attention to the quality of genetic tests, direct-to-consumer advertising and use of personal genomic information."

… is now advocating a policy that would result in precisely the opposite.

After speaking (during the State of the Union and a widely quoted op-ed in the Wall Street Journal) about the need for America to embrace innovation – President Obama is trying to make it more difficult, specifically when it comes to the desire to invest in pharmaceutical innovation – a sure bet under no circumstances.

If innovation is one of the key answers to our national economic recovery, then the President should abide by what he said, “Our economy is not a zero-sum game. Regulations do have costs; often, as a country, we have to make tough decisions about whether those costs are necessary. But what is clear is that we can strike the right balance. We can make our economy stronger and more competitive, while meeting our fundamental responsibilities to one another.”

As Harvard University health economist (and Obama healthcare advisor) David Cutler has noted: "Virtually every study of medical innovation suggests that changes in the nature of medical care over time are clearly worth the cost."

Let’s keep our eye on the prize.  No, not ill-considered budget reduction on the backs of working Americans and seniors – the real prize: better access to smarter healthcare for all Americans. Rather than wasting time on spin, let’s redouble our efforts on innovation.  Then, when we succeed through brainpower and teamwork (and, hopefully some civil bipartisanship), the circus surrounding the President’s tax will be but a footnote in the history of American healthcare.

  Read More & Comment...

Innovation Anyone?

11/03/2011 02:25 PM |

From: CDER Center Director
Sent: Thursday, November 03, 2011 11:17 AM
To: CDER-ALL-HANDS
Subject: FY2011 Innovative Drug Approvals
 
CDER Staff:
 
You may have seen news reports or statements by industry that we are not “innovative,” or that we make it too hard for companies to get a new product on the market. But these broad-brush statements are, in most cases, inaccurate and unfair. They often lack important context that would explain our intentions and the work we do.
 
To help correct these misimpressions, CDER recently collaborated with the Commissioner’s Office, CBER, and many others throughout FDA on a report that highlights the innovative products approved by the agency in Fiscal Year 2011.
 
The report, released today, shows that in FY 2011, for CDER and CBER combined, FDA approved 35 new molecular entities (NMEs).  These include innovative therapies for hepatitis C, late-stage prostate cancer, lupus, drug resistant skin infections, pneumonia, and other serious and life-threatening diseases. 
 
The speed and efficiency with which these products were approved speaks directly to our staff and our high-quality reviews. It also demonstrates our willingness to exercise regulatory flexibility and creative approaches to help industry meet our standards—without lowering them.
 
FDA expedited the approval of many of these products by streamlining clinical trial requirements to permit smaller, shorter, or fewer studies wherever possible.
 
Here are a few highlights of the report:
 
FDA approved nearly half -- 16 -- of the innovative drugs under the agency’s “priority review” program for drugs that may offer major advances in treatment; priority reviews carry a six-month target date for review.
FDA approved all but one of the 35 products on or before the target dates for approval agreed to with industry under the Prescription Drug User Fee Act.
FDA approved the majority of these innovative drugs on the “first cycle,” that is, without requests for additional information that would trigger a second review cycle.
Continuing to enhance our efficiencies remains important, and in the near future I will be sharing with you some ideas on this topic. The positive messages highlighted in this report are a direct result of the combined hard work of all of us at CDER. Thanks to all of you! I am proud and appreciative to be part of the CDER team!
 
To view today's press release and the report, please visit http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm278383.htm
 
FY2011 Innovative Drug Approvals Page: http://www.fda.gov/AboutFDA/ReportsManualsForms/Reports/ucm276385.htm  Read More & Comment...