Recently in Pharma Category

In an unprecedented move, Pfizer is immediately cutting off all CME grants given directly to medical education communications companies (MECCs), according to today's press release from the company. However, Pfizer will honor existing grant committments and will continue to provide financial support for physician-directed CME to healthcare facilities and medical societies.

The move unfairly implies that MECCs, unlike other ACCME-accredited organizations, have specifically undermined the credibility of pharma-supported CME; although Pfizer does nothing more than make the implication. Joseph Feczko, Pfizer's Chief Medical Officer, is quoted: "We understand that even the appearance of conflicts in CME is damaging and we are determined to take actions that are in the best interests of patients and physicians." It is presumed that academic centers or medical societies, unlike like MECCs, confer a desirable credibility to CME.

According to the Dow Jones Newswires, Pfizer spent approximately $80 million last year on CME, with less than half given directly to for-profit MECCs. It is unknown if other pharma companies will follow Pfizer's lead; but if MECCs are to survive the current and impending climate of ill will toward pharma-supported CME, they will need to partner up with academic CME offices or medical societies in jointly sponsored CME projects. In this event, MECCs will no longer need independent accreditation from the ACCME, which at last count accredited 155 MECCs.*

HT: WSJ Health Blog

* Not counting initial or reaccreditation ACCME fees, the loss of annual fees from these 155 accredited MECCs would amount to a yearly loss of at least $310,000 for the ACCME.

Update: On a Pfizer-related note, Derek Lowe at In the Pipeline hears rumors of autumn layoffs at Groton.

In its recently released Policy Announcements, the ACCME proposed that the commercial support of CME should only be allowed to continue in the setting of several changes. These proposed changes stipulated that educational needs and CME content should be specified by a "bona fide" organization that does not receive commercial support. Some (eg, Daniel Carlat) have suggested that these organizations may include those that draft core competencies (eg, the American Board of Psychiatry and Neurology) or, perhaps, practice guidelines. However, a responding question to that definition is Must the authors of these guidelines have no ties to industry? Which begs the follow-up, What is the extent of commercial ties among authors of practice guidelines?

This question is examined in the latest issue of Neurology, which reports potential conflicts of interest (COIs) among guideline authors for the American Academy of Neurology (AAN), the flagship organization of practicing neurologists.* The authors reported that, among 50 clinical-practice AAN guidelines examined, more than 90% had at least 1 author with a potential COI, and almost half of all authors had 3 or more COIs. The breakdown of the types of potential COIs is provided:

• Any, 77% (n = 272/351)
• Research, 45%
• Clinical practice, 42% (ie, practice of clinical procedure within last year)
• Personal income, 33% (eg, fees for consulting, speakers' bureaus, ad boards)
• Equity/stock options, 7%
• Expert testimony, 6%
• Fiduciary role, 3% (ie, officer, director, partner, or manager in company)
• Advocacy role, 2% (ie, payment for advocacy in nonprofit organization or government)
• Patent rights/royalties, 2%

The AAN's most recent Policy on Conflicts of Interest (June 2008) stipulates that COIs may be resolved or lessened by avoidance, withdrawal (either from the commercial relationship or the AAN responsibility), or disclosure. However, given the high rate of disclosed COIs among drafters of the AAN guidelines, it appears impractical and unrealistic to expect avoidance or withdrawal. To that point, the AAN currently indicates that "[d]isclosure is the appropriate remedy for mitigating most instances of [COI]."

Of note, two authors of the Neurology article (Holloway and Miyasaki) disclosed their own potential COIs with commercial entities.

* The AAN does not allow industry employees to participate in the guideline process or direct corporate sponsorship of the process; however, the AAN does accept corporate funding generally.

There are no optimistic forward-looking statements here.

Today, Myriad Genetics announced that its experimental agent tarenflurbil (Flurizan) failed to affect cognition or activities of daily living in early Alzheimer's disease, the primary endpoints of a large (N = 1600), 18-month, phase 3 trial. Tarenflurbil is an NSAID enantiomer of flurbiprofen. The company's CEO reported that, consequently, the development of the compound would be discontinued.

This news follows on the heels of the missed primary endpoints in a phase 2 trial of bapineuzumab in mild-to-moderate Alzheimer's disease, which were nevertheless spun as favorably as possible by developers Elan and Wyeth.

And the Congressional letters just keep on comin'.

This time the target is Murry Kopelow, MD, chief executive of the Accreditation Council for Continuing Medical Education (ACCME), the organization that bestows accreditation on MECCs, medical societies, and universities to deliver certified CME. Senator Herb Kohl (D-WI), chairman of the Senate Special Committee on Aging, sent a letter June 20 (link courtesy of Pharmalot) as part of an ongoing investigation to determine the influence that pharma has on CME. The contents of the letter indicate that Senator Kohl and the Committee have much to learn.

As the Committee continues its examination of the relationship between physicians and pharmaceutical companies, we have become concerned with reports that pharmaceutical companies are increasingly [emphases added] using continuing medical education (CME) events as a vehicle to increase the market for their products.

The opposite is true. Thanks largely to heavy fines exacted by the Office of the Inspector General (OIG) for off-label promotion,* pharma has become decreasingly involved in the development of content for industry-sponsored CME. In my MECC experience during the last several years, pharma has continued to play a decidedly hands-off role in the development of CME programs for which they provide financial support. Some companies have even gone so far as to recuse themselves entirely of reviewing the content (even for medical-legal purposes) before the program is released publicly.

According to the [ACCME] 2006 annual report, commercial support for CME activities accounted for $1.2 million, or half of the budget for CME courses in the United States.

For what it's worth, the most recent number may actually be a little higher, accounting for 60% of the US CME budget.

Of particular concern are instances where drug companies use CME courses to encourage physicians to use their products for potentially controversial medical practice. For example, it has come to the Committee's attention that one pharmaceutical company, which produces an anti-herpes drug, sponsors CME events which promote testing all pregnant women for herpes.

Senator Kohl may consider this nitpicking, but how does a CME program on pregnancy concern senior care? Couldn't the Senator or the Committee's investigators find a more relevant and objectionable CME program?

In any event, it appears that Senator Kohl is referring to GlaxoSmithKline's support of at least one Medscape-produced CME program ("Genital Herpes and Pregnancy"), which expired more than a year ago. GSK is the maker of valacyclovir (Valtrex), which is indicated for "the treatment or suppression of genital herpes [HSV] in immunocompetent individuals and for the suppression of recurrent genital herpes in HIV-infected individuals."

The Medscape program was delivered by Zane Brown, MD, Professor of OB-GYN at the University of Washington, and Serdar Ural, MD, then of U Penn, who (along with the accredited bodies of Medscape and the Medical Education Collaborative) are responsible for the program's content. Brown, in particular, urged HSV testing of all women during early pregnancy, which is based on (according to the program) his data published in the NEJM in 1997, JAMA in 2003, the American Journal of Obstetrics and Gynecology in 2004, and Obstetrics and Gynecology in 2005. Also Brown's experience with a newborn's death caused by congenital herpes (shown in the program) is probably enough for any doctor to mandate HSV testing for all pregnant women in his/her practice.

However, routine testing for herpes in pregnancy is not recommended by any scientific evidence or any national expert panel. In fact, the American College of Obstetricians and Gynecologists, the Centers for Disease Control and Prevention, and the United States Preventive Services Task Force all reject prenatal herpes testing due to the dearth of evidence that exists to recommend routine screening and the potential harm to many low-risk women and fetuses from the side effects of antiviral therapy.

Drs. Brown and Ural may disagree with the Committee (and again, shouldn't we be talking about conditions that affect the aging?) that "routine testing...is not recommended by any scientific evidence." And while it is true that the ACOG, the CDC, and the US Preventive Services Task Force do not recommend routine HSV testing for all pregnant women, this may be a point on which obstetricians reasonably disagree. For instance, in the Medscape program, the majority of program participants (64%) said that they do offer HSV testing to all of their pregnant patients. Dr. Brown also offers the following explanation about ACOG's recommendations to not routinely screen for HSV: "A reason that ACOG is reluctant to issue a new bulletin is because they are concerned about the medical-legal ramifications of widespread screening. On the other hand, I would just ask you to consider a woman whose baby develops a case of neonatal herpes..."

I am troubled by any attempt to persuade physicians to use a drug treatment for any reason other than the patient's condition and the drug's effectiveness in treating it.

Senator Kohl, at least as far as the Medscape program is concerned, appears to be missing its point. The program (as far as I read it) stresses the detection of subclinical HSV during pregnancy to reduce the risk of congenital HSV (which, at the risk of repeating myself, isn't relevant to the aging). Senator Kohl is also probably out of his league here and out of line when it comes to questioning the diagnostic and therapeutic recommendations of physicians (particularly academic physicians)—even if recommended treatment is off-label (which is any physician's prerogative, even duty). I certainly wouldn't want to get into a debate with Dr. Brown on this particular issue.

Therefore, it was with great interest that the Committee took note of the ACCME's credentialing standards and practices for CME courses.

In an effort to better understand the ACCME's credentialing standards and practices for CME courses, please provide us with the following documentation and information.

1.) a copy and written description of the accreditation process for CME courses;

2.) any criteria the ACCME uses, as part of the accreditation process, regarding the scientific validity of course content;

3.) any mechanisms that ACCME has in place to ensure that no undue influence by any industry is being exerted through CME courses; and

4.) any further plans the ACCME may have in place to develop such mechanisms.

Senator Kohl appears to be making a common error here, confusing accreditation with certification. Organizations are accredited by the ACCME to deliver certified CME. An accredited organization (eg, Medscape) certifies the CME programs it produces (and can do so, because it is accredited). Therefore, the ACCME does not oversee the production of individual CME programs and would not have direct oversight of an individual program's scientific validity (nor would the ACCME have the wide expertise that is necessary to oversee the scientific validity of the myriad CME programs). The duty is left largely to the faculty who participate in the content development and delivery of CME programs, as well as the employees of the accredited organization (which are often CME experts and/or health care professionals). The mechanisms that the ACCME has in place to mitigate undue industry influence are contained in the ACCME Standards for Commercial Support. The Committee can find "further plans...to develop such mechanisms" in the ACCME's recent Policy Announcements, a document I absolutely adore. 

MECCs = medical education communications companies.

* For example, see Harris G. Pfizer to pay $430 million over promoting drug to doctors. NYT. May 14, 2004.

The onset of this year's rotavirus season was delayed by 2-4 months, and its magnitude was reduced by more than 50%, when compared with the previous 15 seasons of viral activity. These data coincide with the increasing use of the rotavirus vaccine (RotaTeq; Merck) in infants, according to an early release report from the MMWR. The live, oral vaccine was approved by the FDA in 2006, and its routine administration at 2, 4, and 6 months of age is recommended by the CDC's Advisory Committee on Immunization Practices.

Data from the National Respiratory and Enteric Virus Surveillance System (NREVSS) and the New Vaccine Surveillance Network* (NVSN) indicate that this year's rotavirus season began in late February, while the median onset of seasons during 1991-2006 occurred in mid-November (MMWR figure). Also the proportion of all positive rotavirus tests from mid-November 2007 to mid-April 2008 was substantially lower than the minimum number of positive tests during the previous 15 years.

Percentage of Positive Rotavirus Tests From NREVSS
(Data from 2008 are current through May 3)

According to the CDC, the mean coverage with 1 dose of rotavirus vaccine among 3-month-old infants was 49% in May 2007 and 56% in May 2008. In 13-month-old infants, mean coverage with 3 doses was 3.4% and 33.7% in May 2007 and May 2008, respectively. Rotavirus, the leading cause of severe, acute gastroenteritis in young children worldwide, results in up to 70,000 hospitalizations, 272,000 ED visits, and 410,000 office visits in the United States each year.

*Data are from Monroe County, NY; Hamilton County, OH; and Davidson County, TN.

I've deigned to think differently from Daniel Carlat. 

A fervent critic of all industry-supported CME and the host of The Carlat Psychiatry Blog, Dr. Carlat initially expressed cautious optimism last Thursday about the ACCME's newly proposed guidelines ("ACCME Gets Serious With 'New Paradigm'") to monitor industry-supported CME. However, he showed serious disdain for the very same guidelines 48 hours later ("Using ACCME's New Rules for Bias and Profit"), evidently in response to my criticism on Friday of the ACCME's overblown and confusing verbiage in its document and the organization's apparent failure to entertain the consequences of its proposed actions.

What's somewhat perplexing, other than Dr. Carlat's turnaround opinion, is his not-so-subtle castigation—and even analysis—of me. (So what do I owe you, doctor?) Of course, the absolute gorgeousness of having a blog (other than the fact that I can use words like "gorgeousness" without fear of editing) is that I can respond to Dr. Carlat's post right here on my own little cyber-acre. So here I go.

Dr. Carlat began:

In bmartin's pro-industry-CME blog Pathophilia, there is an interesting post about the newly proposed ACCME rules intended to stamp out commercial bias while still allowing commercial support.

I wouldn't characterize my blog as "pro-industry-CME"; however, I'm not against industry-supported CME, particularly given the current guidelines for its production. Nor am I in favor of stifling the flow of information, whatever its source. It's important to remember that industry-supported CME isn't consumed in a vacuum, but that it exists in the context of commercially supported CME from various industry competitors, as well as a wealth of educational information from nonindustry sources. And doctors are a pretty independent bunch. They can and do decide, individually, what to believe and how to apply information in practice on the basis of a piece of information's provenance and a whole host of other factors, like data reproducibility and clinical experience. Moreover, to my knowledge, there are absolutely no controlled studies demonstrating that participation in industry-supported CME leads to suboptimal medical care or poor patient outcomes. 

Bmartin parses out the wording of ACCME's proposal in order to try to divine the organization's actual intentions, and finds much to ridicule. 

I parsed the ACCME's wording to express my opinion that the ACCME is in love with its own bombastic voice at the expense of meaning. 

You can detect a heavy dose of financial anxiety in this post. It's an attempt to read the tea leaves in ACCME's new policy in the hopes that it will not actually mean any significant changes in the current system. But bmartin ends on a decidedly pessimistic note, predicting that the regulations will lead to less industry funding, and ultimately, to the disappearance of ACCME itself.

Well, maybe Dr. Carlat detects financial anxiety. I thought I was just pissed off at the writing style and lack of forethought of yet another bureaucratic organization.

While I wish I could agree with bmartin, unfortunately I see this as very good news for industry support. Anybody who owns a CME company and has undergone accreditation and reaccreditation (as I have) knows that there is really nothing new in this "new" guidance. Any company will be able to demonstrate compliance with each of these and yet still produce promotional and biased CME. Let's take each of these elements point by point and apply it to a recent promotional CME article produced by Medscape (see here for more details, and see Barnard Carroll's excellent investigative journalism on Medscape here and here).

I'm not sure if Dr. Carlat's implying that I don't know what I'm talking about; however, for what it's worth, I have experienced an ACCME reaccreditation process (which, BTW, generated a lot of printed paper). But more to the point, the ACCME's newly proposed guidelines are different from the existing guidelines (other than the general guideline that content should be free of commercial bias). For instance, there is currently no mandate that educational needs must be identified by an organization that does not receive commercial support—which eliminates most (if not all) MECCs, professional organizations, and university-based CME offices. My main beef with the ACCME's newly proposed guidelines is that they're too vague in how they should or can be executed.

1. Needs assessment will have to be identified by a neutral organization. Not a problem! You want to keep the flow of money coming from Janssen to help it promote Invega? Many non-industry funded organizations will report that practitioners have a need to learn more about the appropriate use of antipsychotics. Bingo—you've just done your needs assessment.

Of course, those in the CME business know that a 1-sentence rationale from any organization is not a sufficient assessment of educational need. Needs assessments are typically multipage documents that include information from literature searches, clinician interviews, outcomes from prior CME programs, physician surveys, and other sources. 

2. Practice gaps will have to be identified by neutral organizations. Same non-issue as number one. Any reasonable organization will identify adequate treatment of schizophrenia as a "practice gap." For example, the AHRQ produced this document which can be cited to support the need for education about how to use atypical antipsychotics. Medscape will argue that focusing an article on treating a schizophrenic patient with liver disease (which just happens to be the specialty of Invega, its sponsor's medication) fills an identified "practice gap," and ACCME won't argue with them.

This point indicates that there are government sources to guide the treatment of conditions like schizophrenia, and that these sources can be used in an assessment of educational need. However, an educational activity that focuses on antipsychotic use and liver dysfunction could not rest (at least, in my experience) on the one generality—namely, that there is a need for education on the use of atypical antipsychotics. But my question to the ACCME would be Must the authors of these government-dispensed treatment recommendations have no ties to industry?

3. The curriculum must be specified by a bona fide organization. This is a hard one...let me see...okay, how about psychiatry's specialty board, the American Board of Psychiatry and Neurology, Inc., which publishes these "core competencies" in psychiatry. Go to the "Somatic treatment" section and you'll find the following recommended curriculum for psychiatrists:

Again, my question to the ACCME would be Is a specialty board, or more specifically, are the drafters of a board's core competencies sufficiently commercial-free? 

4. It must be verified as "free of commercial bias."

This is a redundancy, since this is already a centerpiece of ACCME Standards for Commercial Support. The organization will never have the resources to monitor the thousands of industry-supported CME activities hatched yearly.

Maybe they will; maybe they won't. In my scenario, I guess it's possible that there could be a point of equilibrium, where the dwindling number of CME providers can be sufficiently managed by a beefed-up ACCME—until the organization collapses from lack of fees.

So don't fret, bmartin—in fact, I would argue that this is a cause for great joy. ACCME is handing you the perfect mechanism for a commercial CME whitewash. Use some of that industry money to celebrate.

Okay, it's my turn for analysis...um, bilious sarcasm?

To expand its "operational elements," the Accreditation Council for Continuing Medical Education plans to increase its current fees and to introduce new fees for accredited providers of CME. The ACCME—the US organization that confers accreditation on universities, medical societies, and MECCs to provide CME—stated its intent to increase its revenue in an abstrusely worded annual Policy Announcements. Presently the ACCME's initial and reaccreditation fees are $6500, and its annual accreditation fee is $2000; according to its website, the ACCME provides accreditation for 740 organizations.

The ACCME did not specify its newly proposed fees in the announcements, but additional revenue is intended to support substantial staff increases and "an enhanced monitoring and surveillance system." And while information in this section of the policy document, "An Expansion to Operational Elements," remains vague, it is certainly the clearest in meaning among all sections of the document. Other informational parts of the announcements and proposed policies "for comment" are written in an overbearing, and often senseless, wordiness. Perhaps the ACCME knows what it means; the rest of us can only guess.

Let's begin with the introductory "Accredited CME is[sic] Education That Matters to Patient Care."*

The ACCME continues to emphasize that CME must be a strategic asset to all stakeholders who seek to improve health care in the US. Since 2006, the ACCME has maintained a focus on supporting a well-organized transition to a criterion-based system for the accreditation of CME providers that matches the gaps in physician competence, performance, and patient outcomes (ie, professional practice gaps) with practice-based learning and change.

In the first sentence, I pretty much stumble after "that" and then experience a full-body wince at the use of "stakeholders." In the phrase, "CME must be a strategic asset," "strategic asset" apparently means some important, positive thing; but it's really axiomatic that a cited asset would be important, so the adjective, in my mind, is unnecessary. And then I'd argue that "asset" should be supplanted with an adjective like "important." Then there's the phrase, "all stakeholders who seek to improve health care in the US." That's pretty much everybody, isn't it? So the first sentence can be distilled to something like, "The ACCME continues to emphasize that CME is important to everybody"—which is not a particularly useful or insightful introductory sentence. So just delete the whole thing. 

Then there's the second sentence: "Since 2006, the ACCME has maintained a focus on supporting..." For starters, how about, "Since 2006, the ACCME has focused..." or even "has supported..."? What has the ACCME "maintained a focus on supporting"? A "well-organized transition to a criterion-based system for the accreditation of CME providers." There are at least a few problems with this phrase. The ACCME supports a transition (and not a poorly organized transition, mind you) to a criterion-based system (BTW, it is really just 1 criterion?), but the ACCME doesn't indicate what the transition is from. A non-criterion-based system? Something like astrology? But even an astrological sign is a criterion, albeit a capricious one. So the distinction of a "criterion-based system" is nonsensical without further definition. 

To that point, the remainder of the ACCME's second sentence indicates that the "criterion-based system... matches the gaps in physician competence, performance, and patients outcomes...with practice-based learning and change." The ACCME now defines its "criterion-based system" for accreditation as something that matches gaps—or really, addresses deficiencies—in "physician competence, performance" (which are really the same) and "patients[sic] outcomes." And then the method by which these deficiencies are addressed is "practice-based learning and change." But all medically related learning is potentially applicable to practice, depending on whose practice you're talking about.

So the ACCME's definition of its "criterion-based system" for accreditation (which, when it comes down to it, is not really a system) is the CME provider's act of demonstrating (and I'm helping out the ACCME here) that there is information which has the potential to improve medical practice. Therefore..."Since 2006, the ACCME has supported the accreditation of [or simply "accredits"] CME providers who attempt to provide knowledge that elevates medical practice," or something to that effect. This statement, in its distillation, is also kind of self-evident and, therefore, unnecessary. 

I could go on and on, but the exercise is life sucking. Anyway you get my drift, even if you read only part of the Policy Announcements.

The most controversial aspect of the ACCME's Policy Announcements is in a "For Comment" section, which proposes that the commercial support of CME should only be allowed to continue after several considerable changes. These changes are likely to make the production of timely CME difficult and probably more trouble than it's worth for many providers. (The ultimate and ironic consequence [described below] of the ACCME's proposed conditions should be evident to anyone who has played chess.)

1. When educational needs are identified and verified by organizations that do not receive commercial support and are free of financial relationships with industry.

The ACCME cites government agencies as a example; although, it does not stipulate which government agencies engage in or would engage in the identification of CME needs, or how current CME providers would access or use this information to obtain grant support from industry. Also, what defines freedom from financial relationships?

2. If the CME addresses a professional practice gap of a particular group of learners that is corroborated by bona fide performance measurements (eg, National Quality Form[sic]) of the learners' own practice.

Another ill-considered hoop. Other than citing the National Quality Forum, a nonprofit "performance-improvement" organization, it's not clear what would qualify as valid corroboration. At its website, the NQF notes that it endorses a number of "clinician-level performance measures" and is currently asking for measures related to cancer, infectious disease, and surgical care. But how this information may be obtained or used by CME providers is not described by the ACCME or the NQF. 

3. When the CME content is from a continuing education curriculum specified by a bona fide organization, or entity (eg, AMA, AHRQ, ABMS, FSMB).

Again, how CME providers may obtain and use another organization's curriculum for content is not clear (and perhaps not yet known).

4. When the CME is verified as free of commercial bias.

And who or what determines commercial bias?

Now the big irony of the ACCME's proposed crackdown on commercially supported CME is that it conceivably leads to the organization's undoing through the following process. 

• Industry will provide less commercial support for CME (as has been the case during the last year or so).
• There will be considerably fewer organizations producing certified CME and, therefore, fewer organizations will need accreditation to provide CME.
• Fewer accredited CME providers will reduce the ACCME's fee revenue.

High five, ACCME.

CME = continuing medical education; MECCs = medical education communications companies.

*BTW ACCME, always capitalize verbs, no matter how short, in titles.

Elan and Wyeth announced "encouraging top-line results" from a randomized, dose-ranging phase 2 trial of bapineuzumab in 240 patients with mild-to-moderate Alzheimer's disease; although the monoclonal antibody was no better than placebo when assessing cognition or disability at 18 months, the primary endpoints. A press release from the companies contained the primary-endpoint data in the second paragraph.

Instead the companies chose to highlight results from the post-hoc analyses of subgroups, including patients who do not carry the high-risk apolipoprotein E4 allele (40%-70% of AD patients).* Data in this subgroup showed "statistically significant and clinically meaningful benefits" with bapineuzumab, per cognitive scales like the ADAS-cog. The treated subgroup also demonstrated relatively preserved brain volume on MRI, the press release reported.

Safety data in the phase 2 trial indicated that ApoE4 carriers may be especially prone to vasogenic edema with the agent. Consequently the dose of bapineuzumab, an anti-Aβ agent, is being modified for this subpopulation in phase 3 studies. According to ClinicalTrials.gov, two phase 3 studies of bapineuzumab in AD are currently recruiting subjects, and another two phase 3 studies are "active" but "not yet recruiting."

The Elan/Wyeth press release indicates that full details of the phase 2 study will be presented July 28 at the International Conference on Alzheimer's Disease in Chicago. Despite the mixed phase 2 results, the reaction of Wall Street was mostly optimistic, according to the WSJ Health Blog.

06/18/08 update: According to Forbes, analysts Leerink Swann and Davy Stockbrokers are talking up the study and the companies' prospects. For no particularly good reason, respective share prices of Elan and Wyeth shot up yesterday 10.6% and 4.8%.

Image: depiction of amyloid plaque from National Institute on Aging.

Aβ = amyloid beta.

*So, in this case, we may guess that approximately 12-20 patients per treatment group (4 for bapineuzumab; 4 for placebo) were noncarriers.

Leaders of the Energy and Commerce committee, John Dingell (D-MI) and Bart Stupak (D-MI), requested that 4 drug companies adhere to rules for direct-to-consumer (DTC) ads that are mostly already in place. The letters were sent May 20 to leaders at JNJ, Pfizer, Merck, and Schering-Plough following a May 8 congressional hearing, "Direct-to-Consumer Advertising: Marketing, Education, or Deception?" Responses to the representatives' letters were posted yesterday at the committee's website.

Today's media coverage largely focuses on the representatives' request for a voluntary, 2-year moratorium on DTC advertising of new drug products, which was declined by the companies. However, Dingell and Stupak made other requests, as described in sequence here:

1. That the companies follow the AMA's guidelines for the use of actors and health professionals in DTC ads.

The AMA's policy H-105.988 states that "product-specific DTC advertisements should not use an actor to portray a health care professional...because this portrayal may be misleading and deceptive. If actors portray health care professionals in DTC advertisements, a disclaimer should be prominently displayed." Also "[t]he use of actual health care professionals, either practicing or retired, in DTC to endorse a specific drug or implantable medical device product is discouraged but if utilized, the advertisement must include a clearly visible disclaimer that the health care professional is compensated for endorsement."

The representatives' request is, no doubt, a response to Pfizer's semi-controversial use of artificial-heart inventor Robert Jarvik to promote Lipitor in its now-pulled DTC ads. Pfizer replied to the committee that it is "currently working internally to ensure that the recent AMA guidelines...are fully incorporated into our DTC advertising when applicable." Merck responded that none of its current DTC ads use physicians or actors who play physicians. All companies, including JNJ and Schering-Plough, agreed to comply with the AMA policy in cases where it might be relevant.

2. That DTC ads not market products until a "valid outcomes study" is completed, and the results are released.

The representatives' definition of valid outcomes is not entirely clear; although they may be referring to longer-term clinical outcomes—for example, cardiac events instead of surrogate cholesterol levels in the case of cholesterol-lowering medications (ie, statins). Certainly DTC ads can only promote the use of FDA-approved pharmaceuticals, which must show at least clinically meaningful efficacy and safety to be approved. JNJ wrote that it has concerns about categorically prohibiting DTC ads "before completion of studies of an undetermined time and nature." Merck indicated that it would defer to the FDA on this point. Pfizer and Schering-Plough (which market Lipitor and Vytorin, respectively) indicated that waiting for long-term clinical outcomes would compromise consumer education and, therefore, consumer health.

3. As recommended by the Institute of Medicine, that there be a 2-year (instead of the conventional 6-month) moratorium on DTC ads for new prescription drug products.

In 2006, the IOM recommended that the FDA require a special product label to identify a new drug or new drug combination, and that DTC advertising should be restricted during 2 years. The FDA has not implemented the IOM's recommendation. All companies contacted by the representatives indicated that they abide by a general, internal 6-month moratorium on DTC advertising and would continue to do so. The companies cite PhRMA guidelines, which state that "companies should spend an appropriate amount of time to educate health professionals...before commencing the first DTC advertising campaign...[C]ompanies should take into account the relative importance of informing patients of the availability of a new medicine, the complexity of the risk-benefit profile of that new medicine and health care professionals' knowledge of the condition being treated."

4. That DTC drug ads should not market off-label uses.

Probably the most blatant example of grandstanding by the congressmen. Of course, DTC advertising must comply with FDA-approved labeling, and all companies indicated their compliance.

5. That DTC ads include the FDA's toll-free MedWatch phone number for reporting adverse events.

Current law mandates the listing of the MedWatch number in DTC print ads, and a toll-free information number in televised ads. JNJ indicated that it would include the MedWatch number in its TV ads. The other companies stated that they would defer to the FDA, pending the agency's ongoing investigation of this particular matter.

6. That so-called black-box warnings be included in DTC ads.

Merck and Schering-Plough indicated that they did not have any DTC ads for products with black-box warnings, and all companies replied that they have deferred (ie, Pfizer) or would defer to the FDA about how to incorporate such safety information into DTC ads.

HT for story: Pharmalot. 

On the basis of criteria promoting the treatment of global diseases, GlaxoSmithKline and Novo Nordisk ranked highest according to a newly released index from the Access to Medicine Foundation. The foundation, which encourages pharma's role in the healthcare of third-world citizens, assessed the philanthropic activities of 20 of the world's largest drug companies.

The following table lists the 8 criteria used by the foundation, with examples of commendable policies or programs. Leaders and losers in each category are also provided. By holding up examples, the foundation hopes to 1) motivate lower-ranking companies to establish practices which promote healthcare in developing countries and 2) urge higher-ranking companies to maintain and expand their social responsibilities.

Assessment Criteria	Leading Examples	Leader	Loser
Access-to-medicine management	·     sanofi-aventis: Access to Medicine division within Corporate Affairs; separate from philanthropic activities, drug-donation programs ·     Pfizer: Global Health Fellows Program, in which employees volunteer for 4-6 months at nonprofits in developing world	Novo Nordisk	Teva
Public policy influence and advocacy	·     Eli Lilly: Grant Registry, with disclosure of cash grants to US organizations*	Eli Lilly	Teva
R&D reflecting global disease burden and neglected diseases	·     Dedicated neglected diseases divisions:  GSK, AZ, Novartis, Eli Lilly ·     Tropical-disease vaccine departments: GSK, Novartis, sanofi-aventis ·     Wyeth/WHO collaboration on treatment of onchocerciasis (river blindness)	GSK	Teva
Patents and licensing	·     GSK: licensing agreement with Apotex to produce Apo-Triavir for distribution in Rwanda ·     sanofi-aventis: with DNDi, development of fixed-dose artesunate/amodiaquine	GSK	Pfizer
Drug manufacturing, distribution, and capability advancement	·     Merck: Global Pharma Health Fund and Minilabs ·     Roche: Technology Transfer Initiative	Merck	Schering-Plough
Equitable pricing	·     GSK: "Tearing down the barriers" ·     Merck: tiered pricing policy for HIV drugs based on UN Human Development Index and adult HIV/AIDS prevalence ·     Novo Nordisk: "Base of the Pyramid" pricing initiatives for diabetes	GSK	Schering-Plough
Drug donations	·     Merck: donation of ivermectin (Mectizan) for treatment of onchocerciasis (river blindness)	GSK	Schering-Plough
Philanthropic activities	·     Abbott Lab: Tanzania Care ·     AZ: breast-cancer program with Axios in Ethiopia	Merck	Schering-Plough

HT: Pharmalot.

*As stated elsewhere, Lilly provides a highly itemized (and therefore, very difficult-to-synthesize) online registry report for each financial quarter of 2007.