Post Haste?

08/20/2010 08:42 AM |

Subsequent to the July adcomm on Avandia, the FDA asked GSK to send a letter to doctors detailing what took place.

The first question is … why didn’t the FDA do this itself?  It was, after all, an FDA event.  Was a written synopsis, perhaps, too hot to handle for the folks at White Oak?

To nobody’s surprise, a certain agency employee is unhappy with GSK’s letter.

 “This summary is biased, misleading and not truthful,” Dr. Graham told the New York Times. “The whole purpose of this letter is so that they can reassess whether this is an ethical trial going forward, but the step-by-step ethical flaws and problems with the Tide trial are not even referenced.”

Some panel members agree with Dr. Graham. Panel member Dr. Curt D. Furberg, described the letter as “very Avandia friendly. Panel member Dr. Sanjay Kaul, disagreed, saying the letter “faithfully reflects the deliberations of the Avandia advisory meeting.”

Erica Jefferson, an F.D.A. spokeswoman, said that after ordering GlaxoSmithKline to send a summary of the hearing to the Tide trial investigators, the agency had relied on the company to provide a balanced account. “F.D.A. did not pre-clear or approve the content,” she said.

Mary Anne Rhyne, a GlaxoSmithKline spokeswoman, said the company had only one week to write the 10-page summary, which was necessarily brief. But the company and the leader of the Tide trial agreed that the letter “reflected the science and data discussed at the advisory committee meeting,” Ms. Rhyne said.

Avandia?  Controversy?  Who could have guessed? 

Why didn’t the FDA write this letter?

"Please give me some good advice in your next letter.  I promise not to follow it."

-- Edna St. Vincent Millay

  Read More & Comment...

The Oil Spill of Alzheimer's

08/19/2010 09:49 AM |

If we learn nothing else from BP’s recent unpleasantness, it’s that being able to identify an obvious problem (like when oil is gushing uncontrolled into the Gulf of Mexico) is one thing.  Identifying that there is a potential problem is tougher.  And toughest of all is designing a solution that addresses a need early in the curve.

Case in point, Alzheimer’s Disease. As Gina Kolata writes in today’s New York Times, “The failure of a promising Alzheimer’s drug in clinical trials highlights the gap between diagnosis — where real progress has recently been made — and treatment of the disease.”

Alzheimer’s Disease is a healthcare oil spill of draconian proportion.

Recent significant steps forward in early diagnosis of the disease are important.  And frustrating -- because there is still precious little that can be done when this devastating condition is identified either late in the game or in its nascent stages. 

To say that the science is “hard” (while true) is not particularly helpful.  What needs to be addressed are the twin issues of drug development and regulatory science.  Both are lagging.  Biomarkers notwithstanding, more needs to be done.  We need better tools.  Too many programs  (almost 50%) are failing in late Phase III. Too many programs are mired in regulatory treacle.  The economics are unsustainable from a corporate R&D standpoint and the impact of Alzheimer’s Disease on patients, their families and American healthcare economics is devastating.

Better, more current and predictable scientific research and standards must be developed and devoted to streamlining the critical path. Investment in basic research is not enough. Specifically new development tools are needed to improve the predictability of the drug development cycle and to lower the cost of research by helping industry identify product failures earlier in the clinical trials process.

 

25 years ago, the success rate for a new drug used was about 14%. Today, a new medicinal compound entering Phase 1 testing—often after more than a decade of preclinical screening and evaluation—is estimated to have only an 8% chance of reaching the market. For very innovative and unproven technologies, the probability of an individual product’s success is even lower. We have got to work together to turn that around.

 

When Thomas Edison was asked why he was so successful he responded, “Because I fail so much faster than everyone else.” Consider the implications if FDA could help companies to fail faster. Using the lower end of the Tufts drug development number ($802 million):

 

* A 10% improvement in predicting failure before clinical trials could save $100 million in development costs.

 

* Shifting 5% of clinical failures from Phase 3 to Phase 1 reduces out of pocket costs by $15-$20 million.

 

* Shifting of failures from Phase 2 to Phase 1 would reduce out of pocket costs by $12-$21 million.

 

Investment in basic research is not enough. Specifically new development tools are needed to improve the predictability of the drug development cycle.

 

For all that modern science has to offer, developing new treatments is still very much an art—in which hunches, intuition, and luck play a critical role. The odds are long. For medicine that is affordable and innovative, we need more well-understood science and we need regulatory predictability. And that’s precisely the mission of the FDA’s still moribund Reagan-Udall Foundation.

 

To quote the late Senator Ted Kennedy, the Reagan-Udall Foundation “will make new research tools and techniques available to the entire research community, shortening the time it takes to develop new drugs and reducing costs for patients.”

 

Shortly before his death, I had the privilege of a private meeting with Nobel Laureate Joshua Lederberg. The topic of conversation was the future of the FDA and the agency’s Critical Path initiative. We talked about the state of applied research and “the texture” of the agency, the prioritization of development science, biomarkers and a host of other future-oriented issues. He talked. I took a lot of notes. At the end of the meeting he put everything into perspective in a single sentence. He leaned over the table and said, “The real question should be, is innovation feasible?”

 

I hope so and so should we all.  Innovation = Hope.

  Read More & Comment...

A Seminole moment

08/18/2010 07:59 AM |

A new Orange revolution?

The Florida Medical Association decided Sunday after two days of heated debate not to break off relations with the American Medical Association, officials and delegates said at the conclusion of the event.

Instead, FMA will send AMA a letter describing just how unhappy it is with the national group’s actions on health reform. 

In a formal written statement, Executive Vice President Timothy J. Stapleton said that the FMA letter will convey a vote of “no confidence.”  “The FMA House of Delegates strongly believes that the American Medical Association has failed to represent practicing physicians on the issue of health care reform.”

One of the delegates, Tampa surgeon Michael Wasylik, said, "Doctors are really, really, really upset with the AMA.  Doctors are so angey they can't see straight.

And not seeing straight is a bad place for a surgeon to be.

  Read More & Comment...

FDA's Crude Tools

08/17/2010 04:52 PM |

The FDA makes binary decisions in the main while medical science is quantum knowledge --  which means it's capacity to regulate drugs and devices by adding language to labels or simply pulling a drug because it doesn't benefit -- on average -- all patients relative to risks is outdated.  From Avandia to Avastin the old school view of FDA regulation -- from the right and left -- is prehistoric.    Why is the FDA frittering away millions on discovery work masked as regulatory science and playing footsie with CER when the future is in digitizing and personalizing product development and treatment selection?  And why is the industry funded NIH Foundation lauded for promoting Alzheimer's advances through collaboration and the Reagan-Udall Critical Path Institute is attacked?     I just don't get it. 

marketplace.publicradio.org/display/web/2010/08/16/am-fda-may-revoke-breast-cancer-drug-q/


  Read More & Comment...

Desperate times call for desperate measures

08/17/2010 02:36 PM |

  Read More & Comment...

Of Danes and Deutschland

08/16/2010 07:23 AM |

German authorities have filed charges against pharmacies in the north of the country that have been suspected of purchasing cheap and illegal active ingredients, which they have used to manufacture in-house cancer treatment preparations and then sold them to the general public.

 

Frank Keller, chief investigator of the Technician's Health Insurance Fund (TKK), as saying that the fund had been tipped off that a Danish wholesaler had been supplying German pharmacies with an unauthorized active ingredient for the preparation of an infusion used in cancer treatment. Some 100 of the 400 pharmacies authorized to manufacture the preparation in-house are suspected of having purchased the cheap, illegal product from the wholesaler.

 

Separately, Alexander Retemeyer from the Office of Public Prosecution in Osnabruck, revealed that he had tracked a local wholesaler, which had sourced illegal products from Eastern Europe and then sold them to pharmacies.

 

In the latest revision to the Pharmaceutical Act, the German government has put in place measures to sanction those who introduce counterfeits into the health system. The European Union is also concerned about the increase of falsified medicines emerging in the Member States. Figures from the Directorate General for Taxation and Customs show that counterfeit medicines accounted for 10 percent of goods seized upon entering the EU. Almost 75 percent of these were shipped from the United Arab Emirates.

 

In April, the European Parliament's Environment Committee approved the European Commission's proposal for fighting counterfeit medicines. The committee added a stipulation to the draft, which insists that in addition to preventing counterfeits from entering the legal supply chain and introducing mandatory safety features for prescription medicines, the legislation should prohibit internet sales of “detrimental products.” The EU Parliament will vote on the draft proposal in October.

  Read More & Comment...

The Morning After the Morning After

08/16/2010 07:09 AM |

Per the FDA’s approval of the 5-day emergency contraceptive ella, some perspective. When the FDA reviewed (and reviewed and reviewed) moving the Plan B “morning after” pill OTC in 2003 it was reported as “political interference.” Well it wasn’t true then and it isn’t true now with the approval of a new improved (safe and effective) Rx alternative.  The FDA reviews the science and makes it’s decision. The agency is often imperfect and sometimes contentious.  But it never lacks for passion or intellectual honesty.

  Read More & Comment...

Would Like You Like Fries With That Crestor

08/13/2010 05:36 PM |

Read more here.
  Read More & Comment...

The Urgency of the Critical Path

08/13/2010 07:46 AM |

Why, you ask, is it important to pursue the advance of 21^st century regulatory science?

 

Rare Sharing of Data Leads to Progress on Alzheimer’s Disease

By

GINA KOLATA

 

In 2003, a group of scientists and executives from the

 

National Institutes of Health, the Food and Drug Administration, the drug and medical-imaging industries, universities and nonprofit groups joined in a project that experts say had no precedent: a collaborative effort to find the biological markers that show the progression of Alzheimer’s disease in the human brain.

The complete New York Times story can be found

here.

Fund Reagan/Udall now!

 

 

  Read More & Comment...

Eric Topol Makes The Case for Personalized Medicine

08/12/2010 01:58 PM |

Eric Topol's commentaries in Science and the San Diego Union Tribune underscore the important role commercialization plays in the development, adoption and spread of medical innovations, in this case personalized medicine.  Topol observes the resistance of cliniicians -- and the comparative effectiveness claque -- to genomics as a tool for selecting and enhancing treatment:

"While physicians and the life science industry have done little to advance the use of testing for drug-gene interactions, now the pharmacy benefit managers (PBMs) Medco and CVS/Caremark, which collectively administer the employer prescription plans for nearly 100 million Americans, are stepping up. They are introducing wide-scale genotyping for certain drugs, like Plavix or Tamoxifen, and many anti-cancer medications.

Understatement of the year. 

In his Science article Topol describes as clinical inertia and academic squabbling over methodology continues,   PBMs are setting up the infrastructure for the routine use of genetic testing:

There is a simple way to confirm and quantify the extent of platelet response to clopidogrel, using a variety of point-of-care platelet function tests, each of which has been clinically validated to predict long-term prognosis. Furthermore, the information is highly practical, because patients who do not respond to the antiplatelet drug can have their platelet suppression achieved by using higher doses of clopidogrel or prasugrel (Effient) or by using alternative antiplatelet agents that are expected to be approved in the months ahead. Still, the medical community takes no initiative in routinely genotyping patients who are taking clopidogrel. In March 2010, the U.S. Food and Drug Administration (FDA) put a “black box” warning on clopidogrel that addresses the issue of risk in “poor metabolizers,” as defined by genotyping (8). However, months after this action was taken, it remains exceptionally rare for a patient receiving clopidogrel to undergo genotyping. The lesson here is clear: The medical community is unwilling to change clinical practice and wants more evidence, even in the wake of a significant regulatory body warning.

This reluctance on the part of clinicians has left the door wide open for PBMs. These companies can pitch to their clients—large employers—that they are benefiting their employees by avoiding the use of a drug that won’t work or isn’t being administered at an effective dose. For the exceptionally common clopidogrel medication, which costs $4 to $5 per day, the rationale for more precise use and the avoidance of major adverse outcomes seems attractive. In the next year or two, this medication will become generic, so that routine determination of genotype and, if necessary, platelet responsiveness could provide marked cost savings by avoiding the use of a proprietary drug when unnecessary.

As Eric notes, commercialization carries pluses and minuses, the balance of which could have been enhanced in favor of patients if doctors and researchers had not been engaged in nit-picking and grant seeking.

"Promoting the right drug, the right dose, and the right cost for patients may well improve the competitiveness of PBMs.

But the potential benefits for PBMs go far beyond this pitch. Under the pretext of personalized medicine, these companies potentially may charge patients or insurance companies for genotyping services—for which the market has doubled over the past 5 years —while at the same time also profiting from the drugs prescribed and sold. This may represent a conflict of interest or at least the potential perception of double- or triple-dipping. It will be important for PBMs that pursue such initiatives to be transparent about their genotyping strategies and drug recommendations."

Still, as Topol notes, it is the PBMs and large health plans -- and the DTC firms in their own haphazard way -- making personalized medicine mainstream.  And the long term benefit or externality may be what Ralph Snyderman has envisioned:  the regular use of pharmacogenomic data from the sequencing of our own genome to promote prospective and personalized medicine for specific illnesses.   Unfortunately it seems that clinicians, regulators (now most particularly the comparative effectiveness crowd) and academia (that see their grant receiving status threatened in some strange way by clinical adoption of gene testing) are way behind the curve and out of sync with patients, payors and entrepreneurs.  As Topol notes:

"The lack of alignment will probably be further exacerbated in the next phase of genomic medicine, in which whole-genome sequencing becomes commonplace. The first clinically annotated sequence, albeit requiring a team of 30 investigators and 600 person-hours, demonstrated 63 pharmacogenomic variants of clinical relevance . As more information becomes available from genome-wide association studies that provide actionable data, such as recently reported regarding interferon therapy for hepatitis C , the era for routine pharmacogenomics may finally shift into high gear. In the end, we may ultimately view the surprise movement by PBMs and drugstores as having helped catapult genomic medicine forward. "

Read the full article here.

 

  Read More & Comment...

The Unintended Consequences of Medical Tourism

08/11/2010 07:57 AM |

Not only is so-called “medical tourism” dangerous to the patient –it’s now dangerous to us all.

 

According to a new report, patients who travel to India and Pakistan for cheaper health care may be at risk from a new type of drug-resistant bacteria.

 

Researchers have found a gene that enables the bacteria to resist treatment with a class of antibiotics called

carbapenems in 1.9 percent of samples from patients in the Indian states of Tamil Nadu and Haryana, according to the study in the journal Lancet. Reports from 37 patients in the U.K. who had the resistant strains were also analyzed, and the researchers found that most had received treatment at hospitals in India and Pakistan.

 

In the last three to four years, this kind of resistance has, according to the study, “increased dramatically in India and continues to increase … The possibility of this becoming a global problem very quickly is immense.”

 

Hospitals in the U.K. began reporting cases of patients with this type of resistance in mid-2008, said David Livermore, director of the antibiotic resistance monitoring unit at the U.K.’s Health Protection Agency. In July 2009, the London-based agency issued an alert asking doctors to look out for these resistant bacterial strains in patients who had visited hospitals in the Indian subcontinent. The U.S. Centers for Disease Control and Prevention followed up with an advisory in June 2010.

In addition, medical tourists would be well advised to take their own medications with them.

 

In many places like Turkey, for instance, which is increasingly popular with medical tourists, it takes 2-4 years to register medicines available in Europe or North America.  The result is a strong possibility that in medical tourism “destination locations” the latest and most promising full range of medicines may not be available. This could have consequences prior to, during or post procedure for patients, who may have to rely on older, or less effective medicines than would be offered in North America or Europe.

 

Health Ministries and the medical tourism industry are happy to boast their countries as hot new destinations for procedures, but the ugly under-belly missed by most medical tourists (and not publicly discussed by either governments or “tourism operators”) is the all too often yawning "innovative medicines gap" between home and abroad.

 

  Read More & Comment...

CMI ... TMI?

08/10/2010 08:19 AM |

According to a new study in the Archives of Internal Medicine (Winterstein AG, et al "Evaluation of consumer medical information dispensed in retail pharmacies" Arch Intern Med 2010; 170(15): 1317-13240), The content, formatting, and word count of leaflets pharmacies hand out with medicines leave much to be desired and should be subject to FDA guidance.

Among written instructions given out with sample prescriptions about half failed to include directions on use and raised questions about comprehensibility. "Private sector initiatives to provide useful [consumer medication information] have failed," they wrote. "Research is needed on effective information selection and presentation in terms of effects on comprehension, retention, and appropriate patient actions to derive optimal drug benefit."

The FDA regulates label information and guides that accompany drugs with safety concerns but not the content and format of consumer medication information (CMI) documents. The agency does, however, have a set of eight standards for CMI leaflets:

• State drug name and indication
• List contraindications
• Include directions about use
• Note precautions and potential harms
• List symptoms of possible adverse reactions
• Include general information and encourage patients to ask questions
• Be scientifically accurate
• Be comprehensible and legible

To assess the consistency of these documents, "professional shoppers" filled prescriptions in a national sample of 365 independent and chain pharmacies.

Leaflets for the same product ranged from 33 to 2,482 words, with more than 1,000-word differences among those meeting the highest quality of content. This suggests "large variations in conciseness," the researchers wrote. Less than a third of leaflets used font size of 10 points or larger. Only 10% of leaflets were written at or below an eighth-grade reading level. About 6% of pharmacies didn't provide any written leaflets.

The researchers also noted that chain pharmacies had better adherence to content criteria than did independent stores.

The researchers concluded that the "usefulness of CMI ultimately depends on meeting the needs of patients for information that facilitates the understanding and management of their therapies."

While “more guidance” isn’t always the answer, the FDA should step up to the plate as this is squarely a “safe use” issue.  Helping patients (aka: “consumers”) use medicines as they are intended is the best way to make drugs “safer.”

Knowledge is Power.

  Read More & Comment...

Melissa Healy's anti-statin bias

08/09/2010 01:51 PM |

  Read More & Comment...

Jersey? Sure.

08/09/2010 07:53 AM |

I don’t watch MTV’s “Jersey Shore.”

Maybe it’s because I’m from Long Island (better beaches, fewer tattoos).  Maybe it’s because I’m over 50 (just).  But my kids (ages 19 and 23) are fans – and so are all of their friends.  So, to paraphrase, “it’s the demographic, stupid.”

A recent CMPI survey was of “Millennial” voters (18-28 years old) revealed some very strong – and often contradictory – opinions a -- particularly when it comes to issue of “universal care.”

The national public opinion poll of young voters (the result of 1001completed interviews with adults 18-28 years of age who are registered to vote) shows limited acceptance for the potential consequences of greater government control over health care.

While millennial voters report to strongly support the need for reform and the concept of “universal care,” when asked if they are willing to pay higher taxes to pay for a government-run health care system, their level of support swiftly turns in the opposite direction.

Millennial voters are strongly against government-care that results in longer wait times to see a health care provider, limits to the types of treatments and medicines they can access, and the potential for the government to interfere in the decision making and relationship between doctor and patient.

Some germane findings:

* A majority (51 percent) were not in support of any health care reforms that could raise their personal tax burden;

* Sixty-two percent said they would not support any health care reforms that could increase wait-times to see a doctor or the availability of treatments and medicines; and,

* Millennial voters were also equally unsupportive (62 percent) of health care reforms that would increase the role of the government regulation and oversight in doctor-patient decision-making.

And now we can add Snooki.

Here’s an editorial that ran in the August  7^th edition of the Wall Street Journal:

Democrats Against ObamaCare

The 1099 repeal fiasco, and the Snooki tax.

This wasn't a good week for ObamaCare, with Missouri voting to repeal the law and a Virginia judge refusing to dismiss a serious Constitutional legal challenge. Unlikely as it sounds, however, the repeal movement even came to include House Democrats.

To wit, the House voted last week to repeal one ObamaCare mandate. It might have been the first part of the bill to go over the side, except Democrats rigged the vote so that it failed, even though it got a majority.

The target was an ObamaCare footnote that could wreak havoc with more than 30 million small businesses. In the name of smoking out the illusory "tax gap" of unreported business income, Democrats snuck in a requirement that companies track and submit to the IRS all business-to-business transactions exceeding $600 annually. This 1099 reporting detail received no scrutiny until the IRS's National Taxpayer Advocate Nina Olson exposed the paperwork burden, which would produce no improvement in tax compliance.

Just before the House left town for August, Dave Camp, the ranking Republican on the Ways and Means Committee, offered an amendment that would have rescinded these mandates; as a "motion to recommit," it was guaranteed an up-or-down vote.

Speaker Nancy Pelosi and wingman Sander Levin were terrified that rank-and-file Democrats would defect, so they pulled their entire bill and reintroduced it a few hours later, with the basic Camp language included. In other words, not only was the House leadership unwilling to defend the 1099 provision but it took the lead in rolling it back, if only to prevent an embarrassing floor spectacle.

One catch: The bill was put on the House suspension calendar, meaning it needed a two-thirds majority to become law. In the end, the combined bill shook out 241 to 154, with 239 Democrats voting yea. Most Republicans who favor repealing the 1099 mandate voted no because the final product also included multiple new taxes. Thus Democrats can now say they voted to repeal the 1099 burden without in fact having repealed it.

This is the first of many such moments as the public discovers ObamaCare's many buried land mines. Another example got some attention last week thanks to Nicole "Snooki" Polizzi, one of the idiot savants on MTV's "Jersey Shore." The reality star complained on air that "I don't go tanning-tanning [indoor tanning] anymore because Obama put a 10% tax on tanning, and I feel like he did that intentionally for us." If you've lost Snooki, you've lost middle America.

Democrats sprung this $2.7 billion excise tax on indoor tanning sessions in the final frantic weeks before ObamaCare passed. The 19,000 very low-margin "mom and pop" businesses that comprise the tanning industry don't have much pull in D.C.

This Snooki levy was the first direct ObamaCare tax hike to take effect—the IRS started to enforce it July 1—and like the 1099 mandate, the compliance burden is drastic. The IRS estimates that it takes 36 hours to complete Form 720, which must be filed quarterly. Tanning salons are now trying to reincorporate as gyms, health clubs or "phototherapists" that are exempt from the new tax.

Democrats write all this and more off as "unintended consequences," but tell that to the intended victims. The only way to fix ObamaCare is to get rid of it.

Please pass the sunscreen.

  Read More & Comment...

Hitting the Wall

08/06/2010 07:48 AM |

Novartis got a snail-mail missive from DDMAC for a product-specific FaceBook widget.  According to DDMAC, the widget, that provided a link to content about the Tasigna (a treatment for forms of Philadelphia chromosome-positive CML) omitted risk information and broadened the drug's indication. The widget let users to post links to product information on their FaceBook wall.

DDMAC said the content, in most cases a sentence or two, made claims about Tasigna's efficacy, but did not include any risk information. While the shared content included a link to Tasigna websites, which include risk information, DDMAC said it was not sufficient.

 

"For promotional materials to be truthful and non-misleading, they must contain risk information in each part as necessary to qualify any claims made about the drug," the agency said in the letter.

 

DDMAC also cited the company for not submitting the "FaceBook Share" content for review prior to dissemination, although the company did submit the content contained in the Tasigna website as required.

 

Sounds a lot like the 14 DDMAC letters sent out in November 2009 on the general topic of sponsored Google links.  The key take-away from those letters wasn’t that the agency was condemning the use of social media – but that “sponsored” = “advertising.”  Sound logic.

 

Is a company-sponsored product-specific FaceBook widget advertising?  Of course.

 

The Tasigna letter should not be taken as a signal that the agency is restricting use of social media – it’s a signal that the rules (which, in this case are pretty clear) should be followed.  But, no doubt, those rules need to be clarified.

 

On a more peculiar note (and according to a report in the Pink Sheet), “The agency said DDMAC is not working on draft guidance for issues related to Internet adverse event reporting because it is outside its purview.”

 

That is surprising and disappointing – and requires further thought from the folks at White Oak.

 

  Read More & Comment...

Health Care Advertising Now a Good Thing

08/05/2010 01:08 PM |

  Read More & Comment...

Unsweet 16.3

08/05/2010 08:37 AM |

FDA is predicting a sharp drop-off in fee-paying drug and biologic applications in the current fiscal year.

In a Federal Register notice announcing the fiscal 2011 PDUFA fee rates for applications, establishments and products, FDA estimates it will receive 117.5 fee-paying full application equivalents in fiscal 2010. This figure represents a 16.3 percent drop from the 2009 level of 140.3 FAEs.

(The 2010 projection of 117.5 FAEs is based upon receipt of 88.125 fee-paying FAEs through the first nine months of the fiscal year. On average, 25 percent of the applications submitted each year come in the final three months, the agency says, citing data from the last 10 fiscal years.)

That means 2010 would mark the lowest number of applications submitted since 1995, when 112.5 FAEs were received by the agency. The 1995 figure, however, did not include pediatric supplements, which were exempt from application fees until 2002. When pediatric supplements are factored in, 1994 was the next lowest year, with 115.6.

Why? It’s largely due to a 25 percent decline in applications requiring clinical data. FDA had received 59 such applications through June 30, of which 17 were either exempt or fees were waived, bringing the total number of fee-paying applications to 42. In contrast, during the first nine months of fiscal 2009 the agency received 88.75 applications requiring clinical data, 32.75 of which were fee-exempt or waived, for a total of 56 fee-paying applications.

The total number of fee-paying applications not requiring clinical data declined 23 percent through the first nine months, from 11 last year to 8.5, while the number of fee-paying supplements requiring clinical data fell 5 percent, from 39 last year to 37. The number of fee-paying applications withdrawn or refused to file held steady at .625.

PDUFA implications?  Sure.  But the pure decline speaks to a much more troubling issue:  a parse pipeline.  Now more than ever we need a well-funded Reagan/Udall Center assist us all down the Critical Path.

 And those are capital letters on purpose.

(Hat tip to Sweet Sue Sutter @ the Pink Sheet.)

  Read More & Comment...

Medical Publishing Potboilers

08/04/2010 03:59 PM |

According to wikipedia "Potboiler or pot-boiler is a term used to describe a poor quality novel, play, opera, or film, or other creative work that was created quickly to make money to pay for the creator's daily expenses (thus the imagery of "boil the pot"^[1], which means "to provide one's livelihood"^[2]). Authors who create potboiler novels or screenplays are sometimes called hack writers."

Medical journals are full of potboilers writen by hack writers who today throw together reports designed to fit the media's appetite for stories fitting the anti-Big Pharma narrative...

Case in point: 

Outcome Reporting Among Drug Trials Registered in ClinicalTrials.gov

1. Florence T. Bourgeois, MD, MPH;
2. Srinivas Murthy, MD; and
3. Kenneth D. Mandl, MD, MPH

www.annals.org/content/153/3/158.full

Can you guess what the conclusion of the study was from the following headline?

Review Suggests Bias in Drug Study Reporting

Industry-funded trials more likely to have positive findings than other studies, analysis shows

www.businessweek.com/lifestyle/content/healthday/641567.html

You can spend your own $15 to get this potboiler on line or you can read the juicy parts of the hatchet job here.. You  just have to suffer through my commentary.

"Results were considered favorable if they were statistically significant (based on P values or CIs) and supported the efficacy or safety of the test drug or not favorable if they were not statistically significant for the efficacy or safety of the test drug (25). For noninferiority trials, if the test drug was equal to the comparison drug, the results were also classified as favorable."

An industry sponsored study showing any benefit even if barely statistically signiifcant is considered positive.  An industry sponsored study showing no difference in outcome in treatment compared to another drug or a placebo... that's also called a positive study.

There is also these important findings:

"Trials funded by industry were more likely to be phase 3 or 4 trials (88.7%; P < 0.001 across groups), to use an active comparator in controlled trials (36.8%; P = 0.010 across groups), to be multicenter (89.0%; P < 0.001 across groups), and to enroll more participants (median sample size, 306 participants; P < 0.001 across groups). Government-funded trials were most likely to be placebo-controlled (56.2%), whereas trials funded by nonprofit or nonfederal sources were least likely to be multicenter (24.6%) and tended to have the smallest sample size (median, 50 participants). Industry-funded trials were also most successful at enrolling the anticipated number of participants, with 84.9% of trials enrolling at least 75% of the planned number of participants (P < 0.001 across groups)"

In otherwords,  drug companies did more post market studies (increasingly required) and confirmatory trials (always required) that were more diverse and larger.  That explains in part the higher percentage of trials showing statistically significant efficacy.   Smaller studies that are underfunded and underpowered -- and less likely to enroll the number of patients regarded to achieve a level of confidence that results are reliable:  More likely  early phase studies looking at other endpoints.  No wonder industry sponsored trials are more likely to be "positive."   And just to be sure, the researchers toss treatment toss-ups into the positive category.  Nothing like creating your own standards.   I wonder how many product managers would regard a no-difference result to be "positive." 

So the authors twist the obvious into a conspiracy about how industry funding deliberately puts a happy face on otherwise lousy results...   But in the world of medical publishing, skewing data to stick to pharma is, dare I say, a positive.

So do the headlines about the study, which I bet few reporters even read.  
  Read More & Comment...

Shuren-up Devices

08/04/2010 09:05 AM |

From the Wall Street Journal:

The Food and Drug Administration proposed shoring up medical-device approval rules that have been criticized as lax and inconsistent by consumer advocates and the agency itself.

The FDA aims to better define what devices can use an approval pathway known as 510(k), under which companies can get an accelerated decision on whether they can market a new product if they can show it is similar to an already approved device. The proposals, which will be open for public comment, will be closely watched by the device industry because more-stringent rules would raise development costs.

The FDA's top device regulator, Jeffrey Shuren, rejected suggestions that the changes would result in fewer devices being eligible for 510(k) approval or raise the need in general for extra medical studies. He said clarity was the main point of the effort.

The FDA began reviewing its medical-device regulations in September after issuing a self-critical report that said top regulators bowed to outside political pressure when approving a ReGen Biologics Inc. knee device in 2008. Articles in The Wall Street Journal had pointed to the political pressure and other irregularities in the ReGen case. ReGen said its device was safe and effective and defended its activities before the FDA.

"There is widespread recognition that there's significant room for improvement in the way we operate," said Dr. Shuren, who directs the FDA Center for Devices and Radiological Health.

The FDA said it wants to develop guidance clarifying when older devices shouldn't be used as a benchmark, or "predicate," for comparison to a new product. The agency is still working on the guidelines, but said there appears to be confusion about the rules.

The agency also proposed creating a subset of Class II devices for which clinical or manufacturing data would be needed to bolster the case that they are substantially equivalent to an already approved product. Class II devices are generally considered to carry moderate risk to patients. Dr. Shuren said drug-infusion pumps, ubiquitous hospital products which the FDA is seeking to improve amid a history of problems, fall into this new "Class IIb" category.

Pump maker Baxter International Inc. is in the process of pulling 200,000 pumps off the U.S. market after the FDA decided it was moving too slowly to fix the devices, whose flaws have included failure to deliver the right amount of medicine.

The device industry's trade group said the proposals included a number of steps that would increase the consistency and predictability of the approval process, but as a whole threatened "significant disruption." Among the industry's complaints are an agency plan to include detailed information about new products, such as design schematics, in a public database. That would give foreign competitors access to proprietary information, potentially hurting U.S. manufacturers, said Stephen J. Ubl, president and chief executive of the Advanced Medical Technology Association.

  Read More & Comment...

Total Partial Recall

08/03/2010 09:20 AM |

According to a poll of 802 registered voters by the Pew Charitable Trust's Prescription Project, more than three out of four are confident that prescription drugs made in the USA are free from contamination. However, fewer than one in 10 feel confident about medications made in India or China.

But what “made” represents can be misleading.  On the one hand it means “manufactured.” On the other it means “with ingredients from.”  And the two aren’t the same thing.

This is an important distinction for a number of reasons – especially when you’re asking the question to a general audience.  When you ask someone about their feelings about where a drug is “made,” they are going to assume that “made” means “manufactured.” And while that’s important – it’s only part of the story.

An estimated 80% of the substances used to make or package drugs sold in the United States are made in other countries – and increasingly those “other countries” are India and China. Globally, in 2007, 68% of ingredients of drugs sold worldwide came from India or China, vs. 49% in 2004.

 

As far as products that are manufactured abroad, it’s important for the American public to understand that the exact same GMP’s are required as a plant in the Lower 48.  The Pew poll didn’t share that information. It’s a game changer. 

 

More important is the issue of ingredients sourced from foreign nations.  Heparin comes to mind. (In 2007 and 2008, more than 100 patients in the USA died after taking heparin made with a contaminated active ingredient from China.) Attention must be paid and enhanced oversight is essential. 

 

From the legislative standpoint is the Drug Safety and Accountability Act of 2010, to be introduced today by Senator Michael Bennet (D, CO). The bill would empower the FDA to order recalls of unsafe batches of drugs. This recognizes the reality that the concept of “total recall” of a drug is a  very 20^th century concept.

  Read More & Comment...