Drug Makers Brace for Possible Cuts to FDA

11/15/2010 10:25 AM |

  Read More & Comment...

Quote of the week

11/12/2010 12:59 PM |

  Read More & Comment...

CMPI at Columbus Circle

11/12/2010 12:54 PM |

CMPI at Columbus Circle from CMPI on Vimeo.

  Read More & Comment...

MIT enjoying NEWDIGS "over there"

11/12/2010 08:21 AM |

The European Medicines Agency (EMA) and MIT’s Center for Biomedical Innovation (CBI) and Center for International Studies (CIS) are launching a collaborative research project with a focus on enhancing regulatory science in pharmaceuticals.

Specific questions addressed by this project include how to:

* adapt current regulatory requirements to support the efficient development of safe and effective drugs;

* incorporate patient valuation of health outcomes and benefit-risk preferences into regulatory decision-making;

* implement 'staggered' and 'progressive' approaches to drug approval;

* improve fulfillment of post-marketing regulatory requirements.

The project will explore the feasibility of, priorities for and practical considerations of implementing demonstration projects on some of the issues addressed during the course of the research.

Sound familiar? It's what the FDA's Critical Path program was designed to do -- that is until it hit Congressional treacle embodied by a certain member who will shortly lose her majority status.

The data and recommendations from this project are expected to link to implementation of the Agency's Roadmap to 2015 and the CBI's New Drug Development Paradigms (NEWDIGS) research program.

The project is scheduled to be completed by December 2011.

 Hopefully with a new chair at the helm of the House Agriculture (and FDA) Appropriations Committee, funding for the Reagan/Udall Center can be released and FDA can, once again, take a leadership role in developing the tools for 21^st century regulatory science.

  Read More & Comment...

Remembering Our Veterans

11/11/2010 12:50 PM |

Reagan's D-Day Speech at Normandy Beach still resonates and recalls the courage mustered by everyday Americans to preserve freedom.




  Read More & Comment...

Death rates in U.S. and England

11/11/2010 10:58 AM |

  Read More & Comment...

A Tangled Webb

11/10/2010 10:48 AM |

  Read More & Comment...

Long Time Companion (Diagnostics)

11/09/2010 08:33 AM |

Industry is anxiously awaiting guidance from FDA on the development of companion diagnostics for drugs that will inform efforts to move towards personalized medicine. The agency has vowed to release a draft guidance on companion diagnostics by the end of the year. But the initial document will address development of companion diagnostics for drugs already on the market, not simultaneous drug/diagnostic development for new drugs.

According to Vicki Seyfert-Margolis, FDA’s senior advisor for science innovation and policy:

“One challenge is that multiple centers have to be involved – CDRH and CDER/CBER. The challenge is internal to determine the mechanism for how the applications will come in and how the review is done. I think we are well on our way to figuring out that process between the different centers. With respect to how one designs and qualifies a diagnostic versus a clinical trial, the study design aspects are another challenge.”

“We are also concerned that we will have markers and use patient selection strategies in a clinical trial and then that marker may turn out to be a disease prognostication marker and you may have selected a set of patients that have different metabolisms. There are a myriad of possibilities one could think of that may or may not completely relate to the drug. We just have to be very thoughtful. I think we will evaluate a lot on a case-by-case basis, but we are trying to at least get some information out about what the paths are.”

And then there’s the issue of the “open kimono.”

Ms. Seyfert-Margolis: “One thing I think would be a big win in helping drive personalized medicine and co-development and companion diagnostics will be to open the data. We need to open the data in-house and also strive to get industry to be more transparent and work with us on this. If we took rheumatoid arthritis, for example, and looked across all the trials that have been done with TNF-alphas and evaluated who are the true responders, who are the non-responders, is there anything we can find in all that data that might point to some marker or some diagnostic that could be used, then we could begin to get at least hints about things that could open up new scientific areas for predictive diagnostics.

Amen.  Sounds like a good way to involve the Reagan/Udall Foundation.

  Read More & Comment...

WaPo Provenge Piece Gets The Facts Wrong

11/08/2010 03:34 PM |

What did Mark Twain say:  Get the facts right, then distort them as much as you please.

Case in point:  The WaPo piece on Provenge tinyurl.com/36pvsyn makes two major mistakes.. Actually three.  Naw,  make that four.

1.  It gets the price of Provenge wrong.  It is a vaccine that is administered three times at a retail price of $93k.  Not $270K as cited in the article.

2.  To suggest that the total price of the drug equals a quality adjusted life year (QALY) is absurd.  The chart that goes along with the article is inaccurate and misleading.  Moreover,  a QALY is a rule of thumb developed back in 1985 to estimate the value of dialysis care for Medicare.  To write as if $50K or $100K is a cutoff and a scientific one at at is misleading.  Wrong on both counts then. 

3.  The article states: " In a study involving 512 patients with advanced prostate cancer, Provenge increased median survival from 21.7 months to 25.8 months."  Way wrong and way misleading.   There are patients who have lived for more than five years after Provenge.  And as a legal brief from CareToLIve notes:  " Appellee attempts to underwhelm the Court by stressing a 4.5 month “average” extension in survival to Provenge patients. That understates the effectiveness. Average is different from median. It’s an important distinction because misuse of the term "median survival" is one of the deceptive arguments used by those who are against Provenge approval (FDA). When anti-Provenge forces use the "average" terminology and attribute it to the median, they are undercutting the total Provenge beneficial effect. At the time of the committee meeting it is estimated that the actual average survival benefit in the 9901 trial was in the 10-12 month range, judging from the likely survival through Feb/Mar 2007 of 20 out of the 28 three-year survivors from 10/04. These 20 Provenge arm survivors would have lived anywhere from 5.5 to 7 years after their randomization between 1/00 and 10/01. underwhelm the Court by stressing a 4.5 month “average” extension in survival to Provenge patients. That understates the effectiveness. Average is different from median. It’s an important distinction because misuse of the term "median survival" is one of the deceptive arguments used by those who are against Provenge approval (FDA). When anti-Provenge forces use the "average" terminology and attribute it to the median, they are undercutting the total Provenge beneficial effect. At the time of the committee meeting it is estimated that the actual average survival benefit in the 9901 trial was in the 10-12 month range, judging from the likely survival through Feb/Mar 2007 of 20 out of the 28 three-year survivors from 10/04. These 20 Provenge arm survivors would have lived anywhere from 5.5 to 7 years after their randomization between 1/00 and 10/01.

4.   And WaPo has yet to correct these facts.  It did correct the name of the individual who got the Provenge math wrong. 

And a bonus:  It quotes Sean Tunis and Alan Garber without noting they both were on the Institute of Medicine committee setting comparative effectiveness priorities as well as recipients of CER dough.  (If Garber had his way back in 1992, there would have been no new cancer or orphan drugs since he wrote then that the Orphan Drug Act allows the development of drugs that “do not meet traditional cost effectiveness criteria."  See  Benefits vs. profits:  has the Orphan Drug Act gone too far?  Pharmacoeconomics, 5:88- 92, 1994 and Gaucher Disease Edited by Anthony H. Futerman and Ari Zimran, Chapter 28.
  Read More & Comment...

Fantasy Island

11/08/2010 08:06 AM |

The situation in Puerto Rico just gets stranger.

The latest news is that some leaders of the Commonwealth’s labor movement asked the legislature (on Friday) to amend Law 154 and impose a fixed tax of between seven to ten percent on foreign companies doing business on the island .

(Law 154 imposes a special tax of four per cent on non-resident companies.  That means all of the “Big Pharma” firms doing business on the island.  It was enacted minus any public input or comment.)

The head of the Workers Federation of Puerto Rico, and representatives of the Puerto Rico Central Workers Union and the Brotherhood of Ports Authority Workers claim that a permanent 7 percent corporate tax provide the funds to hire back some of the 20,000 public employees fired due to the island’s economic malaise.

To put that into immediate perspective -- According to a 2006 survey, the biopharma sector supports over 94,000 jobs in Puerto Rico. Talk about fuzzy math. Put 94,000 private sector jobs at risk to rehire 20,000 government workers? What’s wrong with this picture? 

Surprising for many reasons, not the least of which is the recent commitment to the Molecular Sciences Center, the BioProcess Training and Development Center, and the Puerto Rico Cancer Center -- part of a larger effort by Puerto Rico to attract research and development in the life sciences. Raise taxes to increase corporate investment?  Where’s that economic theory being taught?  Faber College?

As Patrician Van Arnum wrote in Pharmaceutical Technology, “Puerto Rico competes with other established areas for pharmaceutical manufacturing investment such as Singapore and Ireland. And China and India, although still emerging areas for pharmaceutical investment, are a consideration for future development.”

Someone should mention this to Governor Luis Fortuño.

  Read More & Comment...

Criminalizing the Doctor-Patient Relationship

11/07/2010 04:17 PM |

Courtesy of  The Happy Hospitalist

Unintended Consequences of Health Care Reform: Everyone's a Criminal But Nobody Cares

Posted: 07 Nov 2010 08:59 AM PST

  Read More & Comment...

Berwick Sticks It To Diabetics

11/05/2010 07:29 PM |

Here's an example of how Donald Berwick is living up to his pledge not to harm one hair on a person's head.

Proposed diabetes changes leave sour taste
By Theresa Flaherty Managing Editor - 10.29.2010           

BALTIMORE - When it comes to diabetes treatment, one size doesn't fit all, stakeholders told CMS medical directors at an Oct. 26 public hearing on the proposed changes to the benefit.

The changes, outlined in a draft local coverage determination (LCD) issued in September, would limit the number of allowed strips, based on frequency of injections, to six per day for insulin-dependent beneficiaries. It would limit the number of allowed strips to one per day for non-insulin dependent beneficiaries.

"It's not that cookie cutter," said Chris Smith, director of policy and regulatory affairs for the National Community Pharmacists Association. "Every individual has different variables that may require them to test more frequently on some days than others."..

But CMS really doesn't care...

"There's a large number of patients we serve that are testing above the (proposed) limits," said Belmonte. "By limiting and not allowing any overages, there could be some clinical implications."

If Medicare won't pay for additional strips, beneficiaries probably won't either, especially those on fixed incomes, Belmonte said.

"I honestly feel that many would choose to sacrifice their health (if they can't) test at what their healthcare provider recommends," she said.

The draft LCD also seeks to require additional documentation regarding physician-beneficiary contact and a testing log maintained by the beneficiary that demonstrates the prescribed frequency for 70% of the testing times.

"(DME providers) can't control what (physicians document) in the record, but without the proper documentation, you are going to have claims denied," said Smith.

Bending the cost curve = sticking it to diabetics, especially those who are poor.

I predict an oversight hearing in January...

www.hmenews.com/
  Read More & Comment...

Some Friday reading

11/05/2010 05:27 PM |

  Read More & Comment...

Where you stand depends on where you sit

11/04/2010 08:30 AM |

The Republican takeover in the House has drug industry stakeholders watching to see which member becomes chairman of a key committee, Energy and Commerce.

First in line for the committee chair is Texas Republican Joe Barton - ranking member since 2007 after Democrats wrested House control in the 2006 congressional elections.

Barton would need a waiver from the party to take the chair, a move considered unlikely following a gaffe this summer in which he demanded President Obama apologize to BP following the administration's response to the Gulf oil spill.

Reps. Cliff Stearns of Florida and John Shimkus of Illinois also are expected to make a play for the top spot, but Rep. Fred Upton of Michigan is currently viewed by Hill observers as the front runner. Upton's donations to other Republicans' campaigns during this election cycle improved his chances significantly.

In two other key House committees - Oversight and Government Reform and the Appropriations subcommittee with FDA oversight - the current ranking Republican member is expected to take the chair.

California Rep. Darrell Issa likely will take the lead on Oversight from Rep. Edolphus Towns of New York. Issa has been vigorous in his criticism of federal agencies under the Obama administration..

Georgia Rep. Jack Kingston is in line to take the Appropriations Agriculture subcommittee from Rep. Rosa DeLauro of Connecticut, who has been the most vocal and consistent advocate for creating a separate food safety agency from components of FDA, Department of Agriculture and other agencies.

Kingston hasn't been a major player on health care issues. But he has made a point of disagreeing with DeLauro's stances. For example, during a 2008 Ag subcommittee hearing on FDA's Safety First initiative on post-market safety. Kingston is "pro-FDA" and would like to hear "more about successes" there, On the down side, Kingston has continued to speak out in favor of importation.

Let the jockeying begin!

  Read More & Comment...

The 1099 "Tweak"

11/03/2010 06:03 PM |

Tweak is the operative word that the liberal spin machine is using to demonstrate their willingness to "improve" Obamacare (another operative word).

It's called tossing a bone.  As in an effort to call off the dogs.

President Obama:

The president said he is still open to hearing some of the Republicans ideas for how to “tweak and make improvements” on the health care system, and mentioned one by name by way of example .

“The 1099 provision in the health care bill appears to be too burdensome for small businesses.  It just involves too much paperwork, too much filing.  It's probably counterproductive. It was designed to make sure that revenue was raised to help pay for some of the other provisions.  But if it ends up just being so much -- so much trouble that small businesses find it difficult to manage, that's something that we should take a look at."

Harry Reid: 

" If there's some tweaking we need to do with the healthcare bill, I'm ready for some tweaking," Reid said in an interview on CNN, after Republicans captured the U.S. House of Representatives in Tuesday's midterm elections.

And the media is taking up the term..

Reuters channels Reid:
 
Republican wins could push healthcare tweaks | Reuters

And NPR has already decided that only "tweaks" to Obamacare are possible:
 
SIDE EFFECTS: Tweaks To Health Law Likely; Repeal Not

Apparently NPR was too fixated on Juan Williams to notice what the election was all about:  George Will provides a take on why "tweaks" are simply the opening bid of the Left to hold on to their taxpayer subsidized sand castles:
 
The progressive agenda is actually legitimated by the incomprehension and anger it elicits: If the people do not resent and resist what is being done on their behalf, what is being done is not properly ambitious. If it is comprehensible to its intended beneficiaries, it is the work of insufficiently advanced thinkers.Of course the masses do not understand that the only flaw of the stimulus was its frugality, and that Obamacare's myriad coercions are akin to benevolent parental discipline. If the masses understood what progressives understand, would progressives represent a real vanguard of progress?...

Will concludes:

Don Boudreaux agreed that interest-group liberalism has indeed been leavened by idea-driven liberalism. Which is the problem.

"These ideas," Boudreaux says, "are almost exclusively about how other people should live their lives. These are ideas about how one group of people (the politically successful) should engineer everyone else's contracts, social relations, diets, habits, and even moral sentiments." Liberalism's ideas are "about replacing an unimaginably large multitude of diverse and competing ideas . . . with a relatively paltry set of 'Big Ideas' that are politically selected, centrally imposed, and enforced by government, not by the natural give, take and compromise of the everyday interactions of millions of people."

This was the serious concern that percolated beneath the normal froth and nonsense of the elections: Is political power - are government commands and controls - superseding and suffocating the creativity of a market society's spontaneous order? On Tuesday, a rational and alarmed American majority said "yes."

  Read More & Comment...

For Pete's Sake

11/03/2010 05:26 PM |

In my desire to get our "Midterm Missive" report done in the late hours following the election, I referred to "Pete Sessions and the Rules Committee" -- but what I meant was "Pete Stark and the Ways and Means Committee."

Oops.
  Read More & Comment...

Midterm Missive

11/03/2010 09:36 AM |

Okay, take a breath.

How many times did you hear the words “historic realignment” over the course of this election cycle? How many times did you hear it when President Obama was elected two years ago?  How many times when the Democrats took control of Congress four years ago?

We can safely assume that, when it comes to “historic realignment,” the phrase has been overused and is largely rhetorical -- unless you are a fan of the Miami Heat.

But that doesn’t mean the midterms are unimportant or unlikely to deliver some real health care-related fireworks.  Au contraire.

When it comes to health care reform and a 21^st century Food and Drug Administration (FDA), will the 112^th Congress be sanguine or sanguinary?  Or is there a third way – of bipartisanship? 

A Republican majority in the House of Representatives means three things:

1. 1- New members – who will need to be educated on many important and arcane policy points;
2. 2- New staff – who will have the power to influence the education of their new masters; and,
3. 3- New committee and subcommittee chairs – who will have the power to call hearings, select witnesses and wield the power of the gavel over some very exigent issues.
4.  
5. Take another breath.
   

Will the 112^th Congress usher in a new spirit of bipartisanship on healthcare reform and a 21^st century FDA?

 

That’s the difference between a hearing aid and a hearing problem.

 

That’s the difference between addressing policy concerns and playing politics.

 

Winners and losers (and not to mention “enemies”) aside, we’ve got an opportunity to work together on healthcare, FDA and a plethora of other issues.

 

Or we can all go down with the (partisan) ship. It’s time for pragmatism.

 

To paraphrase, "Voters, what have you wrought?" "An opportunity -- if you can keep it."

 

For a complete response to the impact of the election, click here to read CMPI's complete "Midterm Missive."

  Read More & Comment...

Healthnewsreview.org: Propaganda Machine For the Dartmouth Gang

11/02/2010 05:55 PM |

Healthnewsreview.org is the self-styled guardian of objective reporting on medicine and science.

It is simply a flack for the anti-medical progress and rationing crowd.

The website is a "project" of the Foundation for Informed Medical Decision Making.  The Foundation is a pass through for HealthDialog, which has turned the Dartmouth belief that one third of healthcare is wasted into a decision tool health plans use to scare people away from things like prostate cancer surgery, hip replacements and other 'wasteful' activities.  Hence, as a project of the Foundation it promote the company line that new technologies should be evaluated in terms of cost and should be covered according to comparative effectiveness methodology.   The site has also helpfully put out a manual for health care reporters to 'guide' them in how to report on medical innovations. 


Healthnewsreview also provides a list of 'independent' experts on health care.  It includes Vera Sharav who runs the Alliance for Human Research Protection..  That's the group that says SSRIs cause suicide.  Very objective and scientific.   And Peter Breggin, who believes medication does not really work for mental illness. 

Also, Marcia Angell, Arnold Relman,  Merrill Goozner and a bunch of other people who make their living consulting for trial lawyers who sue drug companies.

The guy who runs this, Gary Schweitzer, is biased, which is ok.   But he is trying to pass himself off as the arbiter of objective journalism regarding healthcare.

To me, he is a full blown tabloid medicine machine with lots of dough to support him from a company that makes money by rationing healthcare.

Blood money.

 





  Read More & Comment...

From Phase IV to Four Phase

11/02/2010 12:22 PM |

FDA’s new proposed review model would break the process into four distinct phases:

FDA's Proposed Four-Stage Review Cycle

1.     Administrative phase – The agency would validate the application before the review clock starts. 2.     Application review phase – Primary and secondary reviews would take place along with the issuing of any discipline review letters. 3.     Information sharing phase – The sponsor and the agency discuss how to address issues raised during the initial review. 4.     Wrap-up and action phase – Final review activities would be completed.

Under the proposal the agency would not need some extensions it had previously suggested only because the review clock would be stopped mid-review to address application problems and amendments.

A delay by any other name.  This is progress?

The mid-review pause would allow for in-depth discussion between the sponsor and the agency, and appears to be in part a response to an industry request that the review system in the next user fee cycle include a process that makes it easier for sponsors to gain feedback and provide input during an application’s review.

Minutes of an Oct. 12 Prescription Drug User Fee Act negotiation with industry indicated that phase would be used for sponsor meetings with FDA and amendment submissions stemming from reviewers’ issues. The information sharing phase was proposed as a fixed period, although no specific length of time was given.

It would almost certainly be the period where FDA would call its time-out, where the review clock would stop while meetings were conducted.

An application review cycle would begin with the “administrative phase,” where the agency would validate the application before the review clock starts. Primary and secondary reviews would occur in the “application review phase,” along with the issuing of any discipline review letters.

After the sponsor and agency complete the “information sharing phase,” the agency would move to the “wrap-up and action phase,” where final review activities would be completed, including advisory committee meetings, sponsor amendment reviews, risk management agreements, if necessary, and a final decision.

FDA has not determined many details of the new model and minutes called it a “high-level concept.” The agency has not worked out whether the “information sharing phase” would be required for some types of applications that would be considered very likely to be approved or receive a “complete response” letter.

The agency also warned it has not finished refining the concept, so it may not appear superior to the existing review model as it comes into focus. Industry groups at the meeting planned to discuss the new model with their member companies before the next meeting.

The new model is different from any previous compromise FDA has proposed. Agency representatives said in earlier meetings they needed more time than the original PDUFA periods and argued for automatic extensions if advisory committees, foreign facility inspections or certain types of Risk Evaluation and Mitigation Strategies were necessary. The agency also has said any major application amendment should trigger an automatic three-month deadline extension.

Talk about a 90 degree angle!

Under the new review model, the agency would not need three-month extensions for advisory committee meetings or foreign inspections. But it did say a four-month extension still may be needed if complicated REMS was submitted during the review cycle.

Ah – but when during the review cycle should also be a PDUFA reauthorization topic of discussion.

The agency does appear somewhat willing to allow for more Type C meetings in a review cycle, as long as it can control them. “Control” means that the FDA would determine whether a C1 or C2 meeting was appropriate. Industry said sponsors should be allowed to request either classification of meeting, but the agency said it wanted to preserve the standards of what constitutes a Type C meeting. Those standards could be lowered if industry determined the meetings, according to the minutes.

The agency also was concerned the demand for Type C meetings could balloon enough that it would overburden review staff. If the number of meetings eclipsed the 2003 record, the PDUFA workload adjuster, which helps determine annual user fee amounts, would not adequately account for the increase, according to the minutes. If industry accepted the C1 and C2 meetings, the agency said it wanted more resources added early in the PDUFA V cycle to address the workload problem.

Sounds reasonable – but what about a “real time” meeting measurement system to measure if money earmarked results in meetings scheduled?

And what about the issue of so-called “non-binding advice?”

The agency was concerned any provisions allowing non-binding advice would force primary review staff to give advice without supervisory approval or an official record, which could cause an increase in FDA-industry disputes.

Allowing non-binding advice also likely would increase reviewers’ workloads. The agency said some questions that seem simple require input from several reviewers and cannot be answered by one reviewer, according to the minutes.

FDA remained leery about the idea, but was willing to talk about specific parameters where the general scientific discussions that carry no regulatory weight could be allowed, according to the minutes.

Really? Non-binding advice that carries no regulatory weight?

This is progress?  This is transparency?

  Read More & Comment...

The other part of safety & innovation

11/01/2010 08:00 AM |

What does “drug safety” mean?  All drugs have benefits as well as risks – and that’s why we have, for example, REMS and early safety signal communications (worts and all) as well as the FDA’s “safe use” initiative (wherein a drug is made safer when it is used as intended).

But the unsung hero of “safety” is “quality.”

I recently was invited to visit Pfizer’s Kalamazoo production facility. I expected “yawn” – but what I got was “gee!" -- as in GMPs.

What impressed me more than the gee-whiz production aspects of the facility (of which there were plenty) was the dedication of the people who work there – top to bottom.  It actually reminded me a lot of the FDA.  Long-term employees dedicated to serving the public health through dedication to quality.  And they all took it very personally.  Just like at the FDA, the Pfizer folks (many of whom were not only Upjohn legacy employees – but the sons and daughters of Upjohn employees) were on personal missions of quality.  There was a lot of pride on display.

It was all about quality 100 ways to Sunday. And innovation.

But innovation with a twist. 

The Kalamazoo facility makes (among other things) the API for methyl prednisolone, a corticosteroid long off patent.  In fact, it’s been around for about 50 years.  To my surprise, the Kalamazoo plant exports the API to both China and India.

A US manufacturing facility of an innovator biopharmaceutical company exporting API to China and India for profit?  What’s wrong with this picture?

Well, as it turns out, it’s what’s right – innovation through manufacturing prowess, organic chemistry smarts and green technology.  Better.  Faster.  Cheaper.

And also safer – since Pfizer’s figured out how to manufacturer it without preservatives.

Obvious implications for generic manufacturing standards as well as FOBs.

Pharma’s always bragging on its ever-growing investment in R&D.  But when’s the last time you heard about investments in domestic manufacturing? Probably never. And when’s the last time you read about enhanced drug safety through cGMPs and cooperation between industry and the FDA?  Not recently. That’s a shame because they’re two important stories.

Sound like an infomercial? Request a plant tour and see for yourself.

For more details on the Kalamazoo facility, see here.

  Read More & Comment...