Of “Time Outs” and the “Think About It Chair”

10/25/2010 09:22 AM |

And speaking of PDUFA reauthorization – wait, time out.

FDA has proposed a new application review model that would allow it to call a time-out, which could be used to resolve mid-cycle issues.

The idea seems to be an admission by the agency that the six and ten month review times for priority and standard applications, respectively, are no longer sufficient to actually complete a review.

So, it’s not really an issue of “time out” as it is “time on” – as in “time added” at the agency’s discretion.

Minutes of the Sept. 27 industry and FDA Prescription Drug User Fee Act reauthorization negotiation revealed the agency proposed the time-out solution in an effort to create more application review time that will, among other things, allow more feedback to sponsors.

The proposal also could be used to address industry requests for a formal mid-cycle meeting to gain agency feedback on an application’s direction.

But will more feedback result in greater predictability? The length of the review clock stoppage would be fixed, but was not specified in the minutes of the 9/27 meeting.

Industry representatives called for a mid-cycle review in a previous PDUFA negotiating session, but FDA said comprehensive feedback likely was not possible at the midpoint of an application review because its process is not complete. Hm.

An agency willingness to add more meetings to the process is a change from previous discussions with industry, where the agency argued allowing for more meetings could lead to more sponsor questions and create more work for reviewers.

But FDA maintains its previous position that it cannot provide additional application support with the resources it has -- and so its offer for more sponsor-requested meetings means the review time must be extended. Hm.

  Read More & Comment...

Acronyms and Unintended Consequences

10/25/2010 09:04 AM |

REMS, FDA, FDAAA, FTC, ANDA ...

The Federal Trade Commission is looking into whether companies are using REMS to thwart generic competition.

Markus Meier, assistant director of the Health Care Division in FTC’s Bureau of Competition, said he had seen two ways a company may use REMS to block generics: preventing generic companies from getting samples of the drug for bioequivalence testing, or making it difficult for a generic to participate in its REMS program.

“Some systems are so restricted that there is nowhere to buy the product except to buy it from the branded company,” he said. If the branded company refuses to sell it then the generic cannot do bioequivalence testing and therefore cannot file an ANDA and “potentially there will never be generic competition for the product.”

Hm.  “Spirit” of FDAAA notwithstanding, can a company be “forced” to sell its product to a competitor?  Interesting IP question.

Meier said FTC has also seen some instances in which the generic company got sufficient samples and filed an ANDA and then had to come within the branded company’s REMS to start marketing their product. At that point “the branded company tries to impose onerous requirements for participation in the program so that it makes it difficult for the generic to actually qualify,” he stated.

Hm.  But don’t all REMS have to be approved by the FDA?  Minus more directive practices from the agency, well, if you’re not part of the solution …

 “I’m not saying that’s been proven,” Meier added. “I’m not saying we’ve made that accusation of anybody but we’re looking at it. And one of the reasons we’re looking at is because the statute (FDAAA) expressly prohibits participants in these programs from using REMS to erect barriers to competition.”

As for dealing with potential REMS abuse, Meier said FDA does not believe it has any mechanism to enforce the FDAAA provision prohibiting a company from using a REMS to block or delay approval of an ANDA.  But “onerously prescriptive” is certainly in the eyes of the beholder.  Is a REMS that’s tough for the proper public health reasons somehow wrong if it restricts entry of a generic and/or follow-on product? 

Certainly not.   Read More & Comment...

The Same Game

10/22/2010 09:21 AM |

Will FDA tighten standards for generic drugs?  According to CDER Director, Dr. Janet Woodcock – the answer is “yes.”  Good call.

At a meeting of the Generic Pharmaceutical Association in Bethesda, Maryland, Janet said the agency is discussing tightening the limits "so there is less variability.”

Less variability equals better predictability.

Dr. Woodcock commented that patients have complained about generic anti- seizure medications not working as well as brand-name counterparts.

This strikes a very personal note for me.  One of my sons has Juvenile Myoclonic Epilepsy.  His condition is wonderfully controlled via his meds – and I’d like it to stay that way.

Woodcock said that industry executives have approached her with concerns that some generic drugs have spurred quality concerns that went unnoticed in the approval process because clinical testing includes too few patients.

“They say, ‘I know there are products out there that aren’t equivalent,’ and typically they’re manufacturing folks,” Woodcock said in her speech. “I’ve heard it enough times from enough people to believe that there are a few products that aren’t meeting quality standards.”

Woodcock said she didn’t know when the agency would come to any conclusions about generic standards of equivalence. The standards assure the generic is absorbed at the same rate and extent as the brand-name version.

The absorption problems aren’t necessarily harmful, Woodcock said. FDA permits generic drugs to absorb at a 25 percent different rate and extent than the originals they copy.

In April, a group of outside FDA advisers, the Pharmaceutical Science and Clinical Pharmacology Advisory Committee, voted 11-2 that the agency’s equivalence requirements aren’ sufficient for certain medicines. They didn’t offer an alternative, and suggested the FDA list “critical dose drugs,” or drugs where a small difference in concentration can change patients’ reaction, that may need new standards.

The Pharmaceutical Science and Clinical Pharmacology Advisory Committee voted unanimously, with one abstention, that critical dose drugs do constitute a distinct group and voted unanimously that FDA should develop a formal list of those drugs - although the terminology of "narrow therapeutic index" may be more appropriate. And in an 11-2 vote, the committee concluded that current bioequivalence standards are not sufficient for drugs in the narrow therapeutic index group.

Critical dose drugs have a narrow therapeutic index, meaning that "small changes in blood concentration have the potential to result in serious therapeutic failures and/or serious adverse drug reactions." FDA is consulting the committee on the need to establish separate bioequivalence criteria for these drugs given continuing debate about whether critical-dose drugs require special consideration, the agency explained.

Currently, the "sameness" of a brand product and a generic version is evaluated based on two-treatment crossover study to prove bioequivalence, the aim being to show that the 90 percent confidence intervals of the geometric mean test/reference ratios for both maximum plasma concentration and the area under the plasma concentration-time curve fall within a range of 80 percent to 125 percent.

It’s good news that the FDA is taking a strong stance in favor of the public health – because there will be many who seek to undermine this important initiative.

  Read More & Comment...

En Attendant Gudiance

10/21/2010 08:59 AM |

For those of you waiting for FDA to reveal the magical regulations that will unleash the power of healthcare social media – don’t hold your breath.

According to DDMAC Director Thomas Abrams, some social media guidance might be released by the end the year and will address issues related to Internet drug promotion --not how to use specific social media tools like Facebook, YouTube and Twitter

“What we’re going to do is address questions like how to respond to unsolicited requests for information, what’s the corporate responsibility for correcting and monitoring third party sites for misinformation, what’s the corporate accountability for having people post promotional videos and things like that,” Abrams said during a Food and Drug Law Institute conference on enforcement.

And things like that.

 

In other words, and as predicted, the low hanging fruit.

 

Since last November’s Part 15 hearing, DDMAC has communicated that efficacy claims must be accompanied by risk information and cast doubt on the concept of a “One-Click Rule.”  So much for regulations setting pharma free.

 

“In an instant all will vanish and we'll be alone once more, in the midst of nothingness!"

                        -- Waiting for Godot

 

For more on why industry shouldn’t wait for regulatory holy writ, see here.

  Read More & Comment...

Bach Festival

10/20/2010 07:49 PM |

My friend Peter Bach has been one of the busiest and arguably most thoughtful health care policy experts in recent months.  (Then again, as  Red Sox fan, Peter has lots of time on his hands this fall!)   As he knows, I don't always agree with his conclusions but they are always built on scientific research and always thoughtful.  He is also a physician who puts his patients first.   His editorial on the Women's Health Initiative study demonstrating a slight increase in risk of death from cancer in women ages 50-70 who took PremPro is an example of this approach.  He calls for research to investigate the relationship between the likely mechanism and pathways that may be implicated in this reported risk and outcomes in a prospective study.   No one can argue with that.  Or should they.

Peter has written a lot on comparative effectiveness research and has some suggestions about how to encourage it and conduct it in ways that promote better care and less cost.    As the Economix blog put it:  "using the research not to decide whether to cover a procedure but instead to decide how much to pay for it. If there isn’t research showing that a more expensive treatment is more effective than a cheaper treatment, then the reimbursement rate for the cheaper treatment applies to both."  Of course if a more expensive treatment is more effective than it should be paid for. 

I don't trust the motives of many who make up the CER community and believe that CER research contributes nothing to the goal of improving clinical decisionmaking.  Uwe Reinhardt's fippant assertion that differences in clinical pratice can't be controlled for is completely wrong and self serving since Reinhardt endorses using average outcomes of average populations with minimal risk adjustment to decide who gets what.  For Reinhardt's smug analysis:  economix.blogs.nytimes.com/2010/10/15/basing-pay-for-performance-on-outcomes/


  I believe Peter is the exception.   The links to his articles and those written about his work are below.   He offers a sensible starting point for developing an alternative to the CER slush fund.


jama.ama-assn.org/cgi/content/short/304/15/1719

www.theledger.com/article/20101020/ZNYT01/10203007

economix.blogs.nytimes.com/tag/us-health-care-costs/

content.healthaffairs.org/cgi/content/abstract/29/10/1796
  Read More & Comment...

Risk Management Management

10/20/2010 10:09 AM |

Day 2 of the Third Annual Risk Management and Drug Safety Summit focused on the future from a policy perspective -- and why.

 

A few points to share and consider:

 

After the 65 presentations made at the FDA's public meeting and over 2000 docket submissions, it's becoming increasingly clear that not only is the agency's REMS initiative confusing to industry and stakeholders -- but that the problem is, in many ways, one of the FDA's own making.

 

Not that the there's anything wrong with the REMS concept, to contrary, the recent Avandia decision (and, notably, Tysabri) shows the value of a program that provides avenues for both approving and maintaining products with high risk profiles on the market. The problem is that the excesses of the post-Vioxx inquisition have inured many -- specifically practicing physicians -- to any kind of safety warnings.  

 

When important safety warnings become ambient noise, we're facing a dangerous public health situation.

 

Consider the rash of black box warnings proliferated by the agency since the recall of Vioxx. It's the Precautionary Principle come home to roost. Despite the best intentions, early safety signal communications has resulted in a rash of negative unintended consequences: tabloid media reporting, patients scared into non-compliance, labels being increasingly "lawyered-up," and ever-more defensive medical practices that add costs to our already over-burdened healthcare system and birth ever-more (and more obnoxious) 1-800 ambulance-chaser ads. At a certain point, prescribers just stop listening. And that's not good.

 

Someone raised the issue of REMS and federal preemption. The laughter took a few minutes to subside. Bad decisions have negative unintended consequences. The implications of Wyeth v. Levine will be with us for years to come.

 

A related issue is that of product knowledge. What is the real level of understanding physicians have about the products they prescribe -- especially since they are spending less and less time with pharmacy field staff (often by politically-correct dictate).

 

Isn't it time that sales reps begin to "detail the label" to their physician audience? That would be a real public health service -- and also has positive marketing potential. A solid double play.

 

And perhaps it's time for the FDA to measure how the New Labeling Rule (not so new anymore) has impacted prescriber understanding. Such a study would be a whole lot more useful to protecting and promoting the public health than yet another study on the viewing public's understanding of fair balance and adequate provision. (And maybe its time for industry to step up to the plate and rewrite their existing labels in the new format.

 

Relative to PDUFA V reauthorization, it's going to be a tough slog for the FDA to ask for new things when it still has much to deliver on from PDUF IV.  And that certainly includes many risk management issues, REMS included.

 

This becomes even more interesting when you consider the likelihood of different members of Congress wielding the gavel on some committees pretty crucial to the reauthorization process. One issue raised, relative to reauthorization, is the need for the FDA to clarify the when, where and how of the OSE in the review process.

 

The conference ended on a positive and thoughtful note. Rather than a laser beam focus on REMS, perhaps what is required (from both regulator and regulated) is a broader focus on the appropriate spirit of risk management -- of which REMS is only a piece.

 

Perspective.  It's a wonderful thing.

  Read More & Comment...

Let 1000 inititives bloom

10/19/2010 07:03 AM |

CDER Director, Dr. Janet Woodcock gave the opening keynote at yesterday’s third annual Risk Management and Drug Safety Summit.  And it was an address to reckon with.

Some selected comments:

“Safety issues aren’t headlines – they’re biology; a scientific puzzle.”

“The CDER mission is to promote and protect the public health by assuring that safe and effective drugs are available to Americans.”

“Safe does not mean risk-free. Effective does not mean equally for all. We do not have a legislative mandate to consider pricing issues and I doubt we ever will.”

Her four-part definition of “safety”: (1) risks are managed, (2) quality is assured, (3) health fraud is pursued, and (4) advertising is appropriate.

She announced that in “the Fall,” FDA would release several FDAAA-related guidance documents:

–      Guidance that should reduce burdens on the healthcare system of “Medication Guide-only” REMS, while preserving use of Medication Guides to present important information to patients as part of patent labeling

–      Guidance on safety related labeling changes

–      Guidance on Postmarketing Studies and Clinical Trials

Relative to advancing the science of drug safety Janet discussed:

• In silico modeling

• Systems biology

• Animal models

• In-vitro models

• Benefit-risk assessment

She also announced that the agency was creating a new group within CDER’s existing biostatistician office to focus on safety.

She discussed failure modes and effects analysis (FMEA).  Some in the audience whispered that, hopefully, FMEA would do a better job than FEMA.

Janet also shared that morale within CDER “despite what you may read in the press,” is high and has improved since more staff has been hired to more fairly address the workload. 

She addressed the FDA’s participation in the Observational Medical Outcomes Partnership, and many more issues -- all which can all be found in her PowerPoint here. 

And it’s definitely worth a look to any and all interested and/or concerned about the future of REMS specifically and risk management more generally.

Next up was Sir Alasdair, who shared the MHRA’s “pharmacovigilance toolkit. (Note, this toolkit can be found as part of his PowerPoint presentation here.)  It’s elegance and simplicity is in stark contrast to the FDA’s approach, which seems to be “let 1000 initiatives bloom.” 

He made an interesting observation that, in the 1950s, thalidomide was drug safety’s first historical moment and that Vioxx was it’s “second coming.”

He spoke to the Avandia issue by stating that EMA and FDA had reached the same conclusion by reviewing the same data simultaneously.  However, since the regulatory tools of MHRA (as part of EMA) and FDA are different, the results were different.  To wit, while Avandia remains on the market in the US with a REMS, in the EU the drugs license has been suspended.

Sir Alasdair also adroitly addressed the need to move from data management to risk management – a finesse that many in the audience also viewed in contrast to the current FDA approach.

Specifically, he discussed the need to move from reactive to proactive methodology and harness more robust sources of data, moving “up the evidence hierarchy.  And that “regulatory actions should be linked with measurable public health benefit.”

 

It was an information-packed presentation that is worth careful examination by those interested in how the EU is approaching various risk management issues.

The highlight of the morning was a brief, heated (but friendly) Q&A debate Drs Woodcock and Breckenridge on the topic of HbA1c as a legitimate biomarker for Avandia. (Sir Alasdair’s point was that, if Avandia was being reviewed for approval today, HbA1c would not be an acceptable marker.) It was a collegial exchange that should only slightly impact the Special Relationship.

A video of this point/counterpoint will soon be available on www.drugwonks.com.

Juergen Schmider (Corporate Safety Officer and Vice President of Global Pharmacovigilance & Epidemiology at Cephalon) was up next and made some very interesting points about, among other things, off-label promotion – about which he commented, “It used to be a gentleman’s offense, but no longer.

Indeed.

Herr Schmider’s presentation can be found here.

There were a series of other presentations, all of which can be found at www.fdanews.com/RMDSSpresentations.

The day ended on a hopeful and thoughtful note with the following comment from Gary Appio (US Safety Director, Novartis): “We need to advance towards thinking not about risk management, but benefit/risk management.

Amen.

  Read More & Comment...

Today I am a REMS plan

10/18/2010 07:52 PM |

Today I chaired the third annual Risk Management and Drug Safety Summit where I was joined by (among others) CDER Director, Dr. Janet Woodcock and MHRA Chairman, Sir Alasdair Breckenridge.

It was a risk management bar mitzvah in the sense that it felt like REMS was finally coming-of-age – although not yet entirely mature.

Here’s how I kicked off the conference and introduced Janet:

It’s been quite a year on the REMS watch. As Walter O’Malley – the man who moved the Brooklyn Dodgers to Los Angeles once commented, “The future is just one damn thing after another.”

During the course of 2010 there have been both bouquets and brickbats.

Last month the Infectious Diseases Society of America suggested that overuse of antibiotics could be controlled via a REMS-like approach – or even an actual REMS.  If it takes a REMS to drive the safe and appropriate use of antibiotics, then so be it.  Burdensome on docs, yes – but you know the drill.

In July -- Janet Woodcock said “We don't have the kind of standardization and consistency of REMS programs that would be ideal."  Then she announced that the FDA would begin to develop a standard REMS system. Perhaps this will even include a Periodic Table of the Elements to Assure Safe Use.

In June -- John Jenkins, director of the Office of New Drugs -- and the best dressed man at the FDA – admitted that having to develop and then assess the impact of medication guides as part of the REMS program is a burdensome administrative task for the agency.

He said, "We are looking to try and be creative in how we interpret that part of the statute, so stay tuned to see if we're able to find some creative ways around this," he said.

In the meantime, said Dr. Jenkins, "until we work through this further, there are a lot of medication guide-only REMS - a lot of burden on us, a lot of burden on you - that we'd like to try to get out of."

As of June 3^rd, FDA had listed 123 REMS on its website. Eighty-four consist only of a MedGuide, while another 25 involve a medguide and communication plan. The other 14 REMS require sponsors to adopt elements to ensure safe use. Five of those also involve a MedGuide; three also have a communication plan; and the other six also require both a MedGuide and a communication plan.

If FDA does not find a solution to the current MedGuide Malaise, the next reauthorization of the Prescription Drug User Fee Act in 2012 offers an opportunity for legislative change. Industry and other stakeholders already have cited REMS as an area for focus during PDUFA V.

In May -- FDA began designing a five-item grid as a management tool to explain its risk-benefit decisions in a new more concise format.

The grid has five basic factors that need to be addressed. The top two are the seriousness of the condition addressed and the need for a new treatment of the condition. Then comes the traditional heart of the NDA package: analyses of clinical data on the benefits of the drug and the risks associated with its use.

Significantly, the fifth fundamental factor is explicitly the level of risk management associated with the product. FDA is going to take it into consideration in every decision; and sponsors who ignore or underplay the identification of who should use the product and who might use it will have a gap in their filings.

The grid proposal does not call for a fixed mathematical formula behind each approval. Net/Net, the agency has not tried to reduce the role of judgment in approval decisions.

Judgment?  You mean FDA decisions aren’t black and white?  Egad! Someone had better tell Congress.

In the words of John Jenkins, disagreement "happens a lot in the decisions that we have to make. Very few of the decisions that we make on drugs are easy. Very few of the drugs we see have a dramatic overwhelming benefit with relatively no risk. We see that most drugs have marginal to moderate benefits on a population basis and they have general safety but they have the risks of serious toxicities at some low levels." In other words, every decision is "very complex."

Really?

Key take-away is that the FDA is officially moving risk management into the list of key factors affecting new products. And, for better or worse, "judgment" is in the eye of the beholder.

In April -- Biogen Idec announced that it is developing a test that can tell patients their odds of getting PML from Tysabri.

The screening tool could be marketed as early as 2011 if clinical trials involving 9,000 people show a low rate of false findings.

With a false-negative rate of 2 percent, patients would lower their risk of getting the brain disorder PML to 1 in 25,000 for the first three years of their Tysabri therapy. That’s 21^st century risk management.  REMS par excellence.

In March -- Josh Sharfstein suggested, during a House Energy and Commerce Health Subcommittee hearing, that FDA could use more authority to bring negotiations over a drug's Risk Evaluation and Mitigation Strategy to a swifter conclusion.

Josh said, "It's very important for us to work with companies to come up with something that works. There's no question there's a lot we learn from the interchange with companies, but it sometimes can take a long time to come to agreement. Well – that’s a bit of the pot calling the kettle black – but at least it’s an acknowledgement of the problem.

And, of course, there was Avandia.

Let me introduce our first keynote speaker, CDER Director, Dr. Janet Woodcock, by reminding you of what she told this conference last year. Janet said that, “Safety means doing the right things for patients. FDA must consider post-approval issues as part of a drug’s lifecycle.”

Importantly, Janet understands that there’s a real difference between “headlines and help.”  In other words, REMS and other safety mechanisms can be viewed as either “headlines” about “unsafe” drugs or in a more appropriate context of “safe use.”

According to Janet, “FDA does not control the health care system, so our improving the use of marketed drugs, to a great extent, is going to involve influence rather than control.”

“Influence rather than control” is a savvy and sophisticated concept -- one that many of our elected members of Congress could learn from, and one in which REMS plays an important role.

I believe we can also hear the voice of Janet Woodcock in the white paper the agency released a few weeks ago on “Advancing Regulatory Science for the Public Health.

“There is no single discovery — no magic bullet — to address our unique set of modern scientific regulatory challenges. But one thing is clear: if we are to solve the most pressing public health problems we face today, we need new approaches, new collaborations and new ways to take advantage of 21st century technologies. And we need them now.

Ladies and Gentlemen, I am pleased to introduce Dr. Janet Woodcock.

  Read More & Comment...

Chile and The Least Costly Alternative

10/18/2010 10:32 AM |

How would comparative effectiveness be used to justify the Least Costly Alternative in the case of the Chilean miners.

It cost $33 million to rescue 33 Chilean miners.  Each made $12000 a year.   If we use the QALY approach and assume $50000 per QALY it was obviously a waste of Chile's time and money to undertake the successful operation.  Couldn't that money be better spent on disease management programs?  There would be money left over to pay the families of the miners after the mine had been sealed up.  Too bad that Health Dialog didnt have a shared decision making tool to discourage the miners from asking for such an expensive, invasive and untested procedure.   At least Chile should have waited to let AHRQ conduct a CER review before deciding to pay for the rescue. 


  Read More & Comment...

Exchange Rates

10/18/2010 07:07 AM |

When it comes to mandated health insurance exchanges, state officials must strive to ensure that they don’t crowd out free market mechanisms.  Preserving a vibrant private insurance market will maximize choice and enable people to find the insurance plan that best fits their needs.

Healthcare coverage isn’t a one-size-fits-all proposition. 

When President Obama said that people who are happy with their insurance “can keep it,” we should keep him to his word.  Policymakers and private healthcare stakeholders need to work together so that state exchanges don’t become the only way to get health insurance.

Choice is crucial.

See here for a more detailed examination of the slippery slope towards a single payer system.

  Read More & Comment...

What Chile Can Teach Us About Obamacare

10/17/2010 09:27 PM |

  Read More & Comment...

What does Pharma want?

10/15/2010 08:04 AM |

During a past episode of Mad Men, the creative team at Sterling/Cooper is hard at work ideating on a “women’s product” campaign when someone asks, “What do women want?”

Strolling by, Roger Sterling quips, “Who cares!”

Well, when it comes to social media, what does pharma want -- and who cares?

Many will say “regulation from the FDA -- in fact, a great many.  But is that really what pharma wants?

Yesterday I participated in a small roundtable (sponsored by AstraZeneca) on “Examining the Roles of the FDA and the Pharmaceutical Industry in Social Media.” 

(Full disclosure: I ate two small eggplant and tomato tea sandwiches and drank 2.5 cups of organic coffee. I did not offer to reimburse AZ for the “gift.”)

What does pharma want? One of the opening comments was that pharma wants the “ability to engage” in social media.  My response to that was to ask whether pharma has the “will” to engage – because they certainly have the ability if they choose to use it.  And where there’s a will, there’s a way.

Another issue that came up early – and that generated a lot of conversation – was the need to bifurcate the discussion of digital advertising from that of social media. There are rules for digital advertising, paid digital advertising. Social media, on the other hand, is the New Frontier.  It’s the crucial gray zone that exists between regulated speech and user-generated content.  It’s where the rubber meets the road.

What pharma wants (or should want) is specific areas of clarification from the FDA on this new and exciting zone of opportunity.

What of the empowered digital healthcare consumer that we hear so much about?  Well – there were a few of them in attendance at the AZ confab and they had some interesting things to say.

What struck a chord for me was when one of the civilians in the room (by which I mean a patient) said that she really had no idea why pharmaceutical companies chose to absent themselves from disease-related social media conversations.  She assumed it was because Big Pharma is afraid of mixing it up with real people in real time dialogue.

And she’s right, of course – but for reasons she didn’t suspect. The ensuing explanations of adverse event reporting and other compliance-related issues didn’t cause her to nod her head, but rather to say (indeed, almost insist) that “pharma should explain to people why they’re not there.”

Blame the FDA! was the knee-jerk reaction.  But that’s not fair and it’s not true.  How can the agency be blamed for industry’s reluctance to push the boundaries – even a little?   Fear of warning letters?  Fear of unearthing adverse events? I say, where there’s a will, there’s a way. If you won’t blaze the path – even a little -- then don’t expect anyone to know where you want to go.

Unfortunately, blazing new territory through real-time learning is not, shall we say, historically a tradition of the pharmaceutical industry.  Everyone wants to do new and exciting things – second.

Here’s an even more basic question – what’s the right thing to do?  I submit that it’s irresponsible to actively avoid participating in the social media healthcare conversation.  It is, to directly quote CDER Director Dr. Janet Woodcock, “where the people are."  Healthcare begins at search.

 

But, someone pushed back, that’s why we need more directive regulation from the FDA.  I fundamentally disagree (1) that’s what’s needed and (2) that’s what’s coming.  Let me explain.

(1)  IMHO, “We need more regulation” just doesn’t cut it. Since there is no direct “ask” from industry, it’s impossible to expect the FDA to offer direct guidance. It’s not like requesting guidance for DTC advertisements.  That was a precise request for a tangible deliverable that resulted in direct and specific rules and regulation. More regulation?  Be careful, that may be precisely what you get.  Also, “more” guidance means nothing without a more precise reference.  “More” relative to what aspects of social media?  These details were lacking at last November’s Part 15 hearing and (alas) equally so in the lengthier (but equally non-specific) docket submissions.

 

(2)  What are the odds, lacking direction, expertise and experience, that DDMAC will deliver some kind of deus ex machina solution?  Expecting the Holy Grail will only lead to disappointment and frustration.  And blaming the FDA when that happens won’t make anything better or move the social media agenda any further ahead.  If industry is expecting to climb the steps of White Oak on its knees, kiss an FDA relic and miraculously throw away the crutches hobbling their ability to participate in social media, well, there had better be a Plan B.

 

Where there’s a will there’s a way.

 

Then there’s the question of language and syntax.  For example, what does “sponsored” mean? Let’s do a brief thought experiment.  Consider a televised PGA tour event.  When a product logo for an erectile dysfunction medicine appears on the screen and the announcer intones, “This portion of the Masters is sponsored by DRUG NAME HERE,” nobody out there in the viewing audience takes that to mean the “sponsor” has chosen the speed of the greens, the height of the rough, or the pairing of golfers in the tournament.  But say “sponsored” on a social media site and watch the sparks fly at internal regulatory review. Fore! This also leads to the still vague regulatory distinction between property owner and property user – an issue in dire need of FDA clarification.  Discussion of this important social media issue in FDA docket submissions?  Try and find it.

 

Of course, there’s the subtle but crucial differentiation between “permissible” and “appropriate.”  And this returns us to where we started.  What does pharma want?  Do they want social media, primarily, as a new channel for marketing or do they see it as a new and exciting and robust and dynamic mechanism for advancing the public health through real-time interactive communications?

Indeed – why not both?  Where there’s a will, there’s a way.

 

And AZ – thanks for the sandwiches and kudos for a job well done.

  Read More & Comment...

A new wrinkle

10/14/2010 05:02 PM |

The FDA has approved a clinical trial of Botox as a treatment for vaginal spasms that can block sexual intercourse and gynecological examinations.

 

clinicaltrials.gov also lists a similar study that already is under way at the University of Tehran in Iran.

 

The full article can be found here.

I leave the rest to your imagination.

  Read More & Comment...

Advise and Dissent

10/13/2010 08:51 AM |

As Harry Truman opined, “I have found the best way to give advice to your children is to find out what they want and then advise them to do it.”

If only it were that easy with FDA advisory committies.

Matt Herper (Forbes) reports that an analysis of FDA advisory committee recommendations compared to actual FDA actions (from 2007 through 2010) shows that FDA followed adcomm advice 74% of the time. The study, by Concept Capital, looked at a total of 120 product-specific advisory committee votes and the ensuing FDA actions.

Interestingly, the FDA overruled “no” votes only three times: (Tarceva for maintenance therapy in lung cancer, Avastin for breast cancer, and Micardis to lower blood pressure.)

As Herper writes, “In other words, a no vote from an advisory panel is likely to stick, but a yes vote does not mean the product will be approved.”

“Advice is judged by results, not by intentions.”

                            -- Cicero

  Read More & Comment...

Is The Critical Path in Critical Condition?

10/12/2010 04:08 PM |

An article in RPM,  Regulatory Science: A Biodefense Backlash? by Michael McCaughan    tinyurl.com/2byhfxr suggests that the effort to remake product development around 21st century science is stalling or even on life support:

"Securing funding for "Regulatory Science" has been a top priority for Commissioner Margaret Hamburg, highlighted most recently during an October 6 luncheon address to the National Press Club, coinciding with a white paper outlining the agency’s vision for enhancing its science base.

The initiative may be the last hope for the agency to play a central role in encouraging drug development as a core part of its mission, after the underwhelming results from prior efforts like the Critical Path Initiative and the Reagan/Udall Foundation. For industry, "Regulatory Science" funding may be the only hope to secure a pool of resources for the agency to craft policy in areas like companion diagnostics, surrogate markers, etc. without another significant step-up in user fees."

The problem is what money that has been spent is being steered to academic institutions that are not collaborating with either other, with other industry consortium or things on the Critical Path opportunities list.  Further,  lip service is being paid to adoption of new tools and pathways even as the FDA puts out guidances that ignore or fail to encourage their use. The muddled 510k guidance discussion and recent FDA guidance on submission of Phase I safety data are examples of guilt by omission. 

I find myself agreeing with Senator Tom Harkin who expressed concerned about the FDA's increasing set of duties and inability to establish common protocols to speed development of anti-infectives and vaccines within the bio-defense sphere:

Stressing that he was “just thinking out loud,” Harkin suggested that maybe “we need to take something out of FDA, something out of Defense, that would be put under BARDA, and let BARDA be the lead agency.” (Harkin previously noted the “hard work” he and others in Congress put into creating BARDA, and wondered how the new HHS initiative fit within that framework.)

Harkin noted his ongoing frustration with the failure to achieve licensure of cell-based flu vaccines. “FDA just—institutionally, I don’t know if they can do it,” he said. “It is just that they have so much to do and they have other responsibilities, and mostly they are focused on drugs that we take for illnesses.”

That's quite a statement. Unfortunately the organized interests in Washington are more interested in rent-seeking than getting things done. 

Just thinking out loud...maybe everyone needs to redirect efforts towards the development of collaboration to produce the science and regulatory culture required to sustain advances in clinical development and the goal of increasingly effective use of products once on the market.  That's what the Critical Path is and was about.  Discussions about what can be done with fees collected under The Prescription Drug User Fee Act are starting.  

www.fda.gov/ForIndustry/UserFees/PrescriptionDrugUserFee/default.htm

That might be a good time and place to introduce changes in priority and purpose. 

  Read More & Comment...

Britannia Rules

10/12/2010 03:48 PM |

I beat up the NHS often enough so it's only cricket that I point to something transformational that it is undertaking, system wide cancer gene testing that will guide treatment selection and use.  This is something NICE Chair Sir Michael Rawlins has suggested is critical to real health reform anywhere.. 

www.nature.com/news/2010/101012/full/467766a.htm

Cancer-gene testing ramps up
Thousands to get personalized medicine in Britain's National Health Service.

Ewen Callaway

In an approach that many doctors and scientists hope will form the medical care of the future, Massachusetts General Hospital in Boston has for the past year and a half been offering people with cancer a novel diagnostic test. Instead of assessing tumours for a single mutation that will indicate whether a drug is likely to work or not, the hospital tests patients for some 150 mutations in more than a dozen cancer-causing genes, with the results being used to guide novel treatments, clinical trials and basic research. This form of personalized medicine tailors treatments on the basis of the molecular and genetic characteristics of a patient's cancer cells, potentially improving the treatment's outcome.

Now Britain is set to test whether an entire health-care system is ready for the approach. Plans were unveiled this week to deploy broad genetic testing for selected cancer patients in Britain's government-run health-care provider, the National Health Service (NHS). This form of 'stratified medicine' uses genetic information to group patients according to their likely response to a particular treatment.

"The United Kingdom is really the ideal place to do this," says James Peach, who heads the programme for Cancer Research UK, the charity that is leading the effort. As the NHS treats millions of people each year, unprecedented numbers of suitable patients could be enrolled in the genetic-profiling programme. "The idea is to scale this up to every patient in the NHS," says Peach. In its first phase, the programme will be rolled out to as many as 12,000 NHS cancer patients over two years, beginning in early 2011. By contrast, Massachusetts General has tested about 1,600 patients, and other hospitals' efforts each number in the hundreds.

The tests, which will look for several dozen mutations in about a dozen genes linked to cancer, will be carried out on people with lung, breast, colorectal, prostate or ovarian cancers, or metastatic melanoma, who are being treated at six NHS hospitals. Therapies that target specific tumour-causing mutations have already been approved, or are on the verge of approval, for most of these conditions, says Peach.

Testing a clinical sample for so many mutations at once is a challenge in itself. Because most existing clinical tests probe individual genes, the NHS programme is working with the Technology Strategy Board, a government agency that supports technology development, and several companies to design a customized test that detects all of these mutations in one go. The partnership, which includes the pharmaceutical multinationals Pfizer and AstraZeneca, will also design software to make the results useful to researchers and clinicians. By genotyping patients for a broad array of cancer-causing mutations, the new tests will make it easier to assign subjects to clinical trials, Peach says.

That is already happening at Massachusetts General, where the test is helping to establish clinical trials that wouldn't otherwise have happened, says Leif Ellisen, a geneticist who helps lead the hospital's cancer testing programme. For example, its broad genetic test detects a mutation in a gene called BRAF that is already known to be commonly mutated in metastatic melanoma. Finding such mutations in people with lung and colon cancer made it possible to put them in a trial of an experimental treatment targeting that gene, Ellisen explains.

Basic research should also benefit from the NHS programme, says Peach. Researchers will have access to consenting patients' genetic data as well as to medical records of the outcomes of the treatment. These data could reveal how drugs targeting one molecular pathway are affected by mutations in another gene, says Andy Futreal, a cancer geneticist at the Wellcome Trust Sanger Institute in Hinxton, UK, and an adviser to the programme.

Peach hopes that the first phase of the cancer programme will pave the way for expanding genetic testing to more patients and other conditions, such as diabetes, AIDS and even psychiatric disorders. Cancer offers a good testing ground for personalized medicine, because numerous targeted therapies already exist, but "there's no reason why this should be restricted to cancer", says Peach.

Fabrice André, who runs a similar cancer diagnostic programme that has so far been offered to about 100 patients at the Gustave Roussy Institute in Villejuif, France, says the NHS programme could point the way to implementing personalized medicine across an entire population. "It can really change the landscape of how molecular testing is being done for cancer," he says. "If they succeed, then it's going to be a major step forward."


  Read More & Comment...

Up Close and Personnel

10/12/2010 07:53 AM |

The Office of Personnel Management (OPM) is planning a new database that will store health care claims information from three federal programs - the Federal Employees Health Benefits Program, the National Pre-Existing Condition Insurance Program and the forthcoming Multi-State Option Plan.

 

OPM (in a 10/5 Federal Register notice, says the database will allow OPM to "actively manage all three programs to ensure the best value for the enrollees and taxpayers." The database will be effective Nov. 15 "unless comments are received that would result in a contrary determination."

 

OPM?  Healthcare “value?”  This raises two issues:  (1) expertise and (2) mission creep. Are people being hired to do this?  Who are they? Who’s choosing them? Transparency is required – if not a Congressional hearing.

 

Information collected will include personal identifying information, address, dependent information, employment information, health care provider details including debarred provider information, health care coverage information, health care diagnosis information and provider changes and reimbursement on the aforementioned coverage, procedures and diagnosis.

 

OPM?  Really?  Sounds like a CMS program – or even AHRQ.  Also, will this data be shared with other federal agencies?  And if so, to what end. 

 

Per the FR notice, "the data will be de-identified for specific analysis that provide flexible queries of the data set for general demographic queries, risk-adjusted profiles, and comparison of chronically ill patients and other useful analytics; and engage in econometric modeling of, among other things, health trends, risk adjustment methodologies, pharmacy pricing and negotiation."

 

Hm – “econometric modeling?”  That sounds menacing.

 

Yes – definitely Congressional hearing material.

  Read More & Comment...

Health Affairs Skews Survival Statistics To Support Obamacare

10/11/2010 02:56 PM |

Compared to other developed nations, United States has better survival and life expectancy rates for cancer, heart disease and stroke according to analysis of validated registry and clinical data.   When absolute differences in smoking are controlled for, life expectancy after age 50 in the US is better still.  The critical difference: Americans are receiving more effective treatments more often.

So if you want to claim just the opposite: that spending on health care is not related to life expectancy or want to show that the US healthcare system needs to control costs by allowing the government to "coordinate care?" 

You do what Sherry Glied and Peter Muening did in their widely publicized article in Health Affairs, "What Changes In Survival Rates Tell Us About US Health Care".   You come up with a 15 year survival rate which understates the effect of treatment since most studies track 5 year survival rates after diagnosis and treatment and overstate behavioral issues.   Then you simply assert -- because there is more spending in the US than Europe -- that the difference is the result of our lousy, inefficient system of care. 

content.healthaffairs.org/cgi/content/full/hlthaff.2010.0073v1#SEC1

How do the authors get away from making the exact obvious conclusion that the rest of the epidemiological literature has shown?  One reason is that Health Affairs is carrying a torch for Obamacare and whatever peer review took place was passive or unconcsious.  Another reason:  such statistical skewing is easy to get away with because most in the media simply report the conclusion without looking at the methods.

The authors state: "We measured fifteen-year survival rather than life expectancy because the latter can be biased by the survival experiences of a small number of elderly people, among whom coding errors are common. Focusing on survival also allowed us to distinguish between the experiences of specific cohorts. We explored fifteen-year survival for men and women separately because risk-factor profiles differ greatly by sex and country.

By looking at overall survival after 15 years the authors can go back to a time when medical innovations essential to survival by disease were non-existent but detection in the US was more prevalent   The effect of higher levels of detection -- in the absence of innovations -- are what appears to be lower rates of survival.   At the same time they ignore mortality rates because the US had a faster decline in mortality from major diseases (many of which Glied and Muenning ignore) than in other countries. 

This hatchet job has yet to be questioned by anyone in the media.  If anyone is interested they can compare the Health Affairs j'accuse with other studies that are less biased. In particular, look at Low Life Expectancy in the United States: Is the Health Care System at
Fault? by Samuel H. Preston and Jessica Y. Hoy of UPenn.


repository.upenn.edu/cgi/viewcontent.cgi


  Read More & Comment...

Death Ray

10/11/2010 08:29 AM |

Been warning about this from the very beginning, and now it’s starting in earnest:  Cost-centric strategies leaving patient-focused medicine in the dust.

Last week the Medicare Payment Advisory Commission met to consider recommendations that empower Medicare to reinstate the option to base Part B drug reimbursement on the least costly alternative (LCA) among products.

Note please, that “least costly” in no way means “best for the patient.”

On October 7^th, MedPAC heard two proposals outlined by commission staffer Nancy Ray.

The first was that Congress should give CMS authority to apply least costly alternative policies in setting payments for items and services covered under Medicare Parts A and B, and CMS should periodically assess the clinical similarity of Medicare-covered services and apply LCA policies for those services deemed clinically similar.

The second was that Congress should direct CMS to set the payment rate for a newly covered service that lacks evidence demonstrating better outcomes than existing treatment options at a level that is no higher than the LCA.

The policy could end up relying heavily on data from comparative effectiveness research conducted under the auspices of the Patient-Centered Outcomes Research Institute, which is being created under the Affordable Care Act.

A provision of the ACA states that HHS cannot deny coverage of items based solely on the results of comparative clinical effectiveness research, presenting a possible gray area should LCA determinations favor one product over another.

Ray predicted that both of the LCA recommendations would decrease spending relative to current law and also would lower beneficiary cost sharing in the short term and Medicare premiums in the long term.

While the commission did not vote on either recommendation, comments from members were generally supportive. Surprised?

If you needed another reason to understand why the upcoming elections are so crucial to 21^st century patient care – you’re welcome.

  Read More & Comment...

Obama Repeals Obamacare

10/08/2010 02:34 PM |

By granting waivers to avoid forcing nearly 3 million people to lose coverage, the Obama administration has started towards the repeal of Obamacare. Note that this is only a waiver to increase annual minimum coverage levels for mostly part time, young and temporary workers.  The next tsunami to hit will be when plans inform HHS it will drop coverage because of the mandate to spend up to 85 percent of medical premiums on what Obama defines as quality care.    If the administration continues down this road it can take credit for "creating or saving" coverage for 20 million Americans...

You can see the first evidence of Obamacare repeal by Obamacare here:

www.hhs.gov/ociio/regulations/patient/appapps.html
  Read More & Comment...