Ethics: August 2008 Archives

Thanks to the Drug and Device Law Blog for providing a link to the opinion of New Jersey federal judge William Martini in the case of Gunvalson v. PTC Therapeutics. Comment on the reported opinion, which concerns access to an experimental drug for Duchenne muscular dystrophy (DMD), was made in a previous post, and follow-up information from a primary source is always welcome—particularly when plenty of questions about the case remain unanswered.

One notable issue raised in the opinion (page 7), which is pretty much dismissed by the judge, is whether the plaintiff, Jacob Gunvalson, even has DMD or, instead, a related and less severe condition, Becker muscular dystrophy (BMD). The distinction is important because the 2 conditions depend on the nature and consequence of the mutation in the gene that encodes the dystrophin protein. Deletion mutations in the gene that cause an out-of-frame mRNA transcript are likely to produce nonfunctional dystrophin, which manifests clinically (in general) as the more severe DMD. Patients with BMD are believed to produce partially functional dystrophin, which accounts for the milder illness.

The nature of Jacob Gunvalson's dystrophin mutation (if detectable), his dystrophin production, and the clinical severity of his illness are important (if not crucial) for 1) anticipating whether PTC's experimental suppressor of nonsense mutations, PTC124, is even likely to work; and 2) ensuring the clinical uniformity of enrollees in clinical trials (if patients with BMD are not eligible).

I can only assume that these issues were laid aside by the judge because either 1) he is incapable of understanding them or their importance; 2) they weren't argued sufficiently by the defendants; or 3) they're resolved issues in the minds of the defendants (meaning that Jacob Gunvalson is known to harbor a nonsense mutation and, indeed, had DMD). [See information in the Addendum below, which suggests that Jacob's diagnosis is not resolved.]

Alright, those fundamental medical concerns raised, back to the opinion:

The undisputed background on the case is that, in early 2006, PTC began a 28-day, open-label phase 2a trial of PTC124 in patients with DMD. At the time, Jacob was taking the well-known aminoglycoside antibiotic gentamicin, which is known to suppress nonsense mutations. (It is unclear how Jacob was receiving gentamicin: from his personal physician or through a clinical trial.) According to the opinion, Jacob's mother consulted PTC vice president Claudia Hirawat about whether Jacob should discontinue gentamicin, so that he could enroll in the PTC124 clinical trial. (Why Hirawat, who is evidently not a medical professional, would be consulted over Jacob's personal physician on this issue is not known, nor addressed, in the opinion.)

According to the affidavit of Jacob's mother, Hirawat told her that Jacob should continue the gentamicin, "which appeared to have some beneficial effect, and wait for later PTC124 clinical trials." This is the alleged exchange (along with similar exchanges) on which the entire case apparently rests: Whether PTC (as represented primarily by Hirawat) led Jacob and his mother to believe that Jacob would have access to the unapproved PTC124, even though he was advised not to and/or didn't enroll in the phase 2a trial of PTC124.

As it turns out, the phase 2a trial was a "success," as Judge Martini describes it. (Frankly it's hard to call such a small, early-phase trial a success—unless by success, one means "not a failure.") According to the PTC web site, enrollees with DMD and a nonsense mutation in the dystrophin gene received 1 of 3 dosages of PTC124 for 28 days. Data from 26 patients who received low or medium dosages were presented at the Third Annual Congress of Myology in May. 

Muscle biopsies showed evidence of dose-dependent increases in dystrophin expression and significant reductions in creatine kinase levels. Also parents and teachers reported clinical improvement in this non-blinded, non-placebo-controlled study, and the drug appeared to be reasonably well tolerated. Given the positive phase 2a trial results, a 2-year extension phase was initiated. 

At this point in time, Jacob's clinical status had deteriorated, according to the opinion, but it does not describe how. (News reports suggest that Jacob had become nonambulatory.) Consequently Jacob sought access to PTC124; however, he was not eligible to participate in the 2a extension trial, because he had not been enrolled in the 28-day study (which PTC had discouraged, claimed the Gunvalsons).* Therefore the Gunvalsons sought access to PTC124 through the FDA's compassionate-use program, which PTC refused to pursue. 

By my read, Judge Martini bases his opinion in favor of the Gunvalsons primarily on whether PTC created some kind of legal obligation to provide PTC124 to Jacob. The judge refers heavily, on this issue, to the affidavit of the patient's mother, Cherie Gunvalson, and what was said and/or promised to her by PTC employees, specifically Hirawat. However, Hirawat's statements, as quoted by the judge, provide an important caveat to clinical-trial enrollment that is overlooked (in my opinion) by the judge. For example,

I informed Mrs. Gunvalson that Jacob's non-enrollment in the phase 2a trials would not by itself preclude him from participating in all of PTC's anticipated future clinical trials, for PTC 124, assuming he satisfied the eligibility requirements for those trials [emphasis added].

It is also important (at least to me) that this statement does not promise enrollment in the 2a extension trial specifically (although some may consider this point too fine to care about). In addition, the accurate quotation of other statements allegedly made to Jacob's mother are suspect, in my mind. For instance, PTC chief medical officer Langdon Miller is claimed to have promised unqualified access to PTC124, a dubious proposition: "[O]nce positive results were back from the [phase 2a] trial, Jacob will get PTC124."

Lawyers Jim Beck and Mark Hermann, over at the Drug and Device Law Blog, dissect some of the legal issues in the case—such as the advisability of communications between company representatives and patients and the nontrivial nature of opening a compassionate-use program for an individual patient. They also make a lot of decent-sounding arguments for why Judge Martini's opinion is a raw deal for any company that develops drugs for hopeless conditions. 

* A previous post discusses Jacob's enrollment in a phase 2b trial of PTC124; however, a footnote in Judge Martini's opinion dispels any notions that either party thought Jacob was or is eligible for enrollment in this trial (see opinion footnote, page 3).

Addendum: In its press release on Judge Martini's opinion, PTC writes, "The decisions made about prior trials were decisions made by the Gunvalsons or the principal investigator for that trial, and not based on any promises or assurances by PTC. In fact, medical records and emails from the Gunvalsons also indicated that Jacob was ineligible for our Phase 2a trial because of the specific nature of his medical condition."

Evidently Richard Finkel, MD, principal investigator of the 2a trial of PTC124, believed that Jacob had BMD on the basis of a record review. A diagnosis of BMD would have disqualified Jacob from PTC's 2a trial, according to Finkel (see page 7 of Martini's opinion). However, another principal investigator, Brenda Wong, MBBS, MRCP, believed that Jacob had DMD. The judge conferred greater weight to Wong's diagnostic opinion.

Physicians have been arguing about pharma's influence on postgraduate medical education for at least 50 years, reveal Scott Podolsky, MD, and Jeremy Greene, MD, PhD, in last week's JAMA. The Harvard physicians' commentary, "A Historical Perspective on Pharmaceutical Promotion and Physician Education," is intended to provoke cautionary thought about the future of medicine, given industry's longstanding involvement in and financial support of the dissemination of drug information.

However, the fact that a 50-year argument on the subject goes on merely indicates this: There's still no tangible evidence that pharma's potential influence on continuing medical education (CME) alters physician competence or patient outcomes—for better or worse.

In the closing of their JAMA commentary, Podolsky and Greene quote advertising executive Pierre Garai from 1963: "We know what the doctors are today. What will they be tomorrow?" This originally rhetorical question cannot be answered, of course, for today's physicians; but it can be addressed for physicians who were practicing during the early 1960s.

Therefore we can ask, what untoward healthcare event has occurred during the last 45 years as a result of pharma's influence on CME?

The only event that comes to mind (to which Podolosky and Greene also allude) is the overuse or misuse of antibiotics, ostensibly as a result of pharma marketing injected into industry-funded CME. However, a search of the medical literature does not support this contention (although an exhaustive search, for the purposes of this blog post, cannot be guaranteed).

On the other hand, a survey of Georgia pediatricians, discussed in a 1999* issue of Pediatrics, indicates that the decision to prescribe antibiotics for children is influenced by 1) diagnostic uncertainty (ie, Is the illness viral or bacterial?); 2) sociocultural and economic pressures (eg, consideration for time-strapped working parents); 3) fears of malpractice litigation; and 4) parental expectations. While the surveyed physicians may have been reluctant to admit to the influence of pharma-funded CME on their prescribing behavior, it seems unlikely that this potential influence would supersede the practice considerations cited by the surveyed physicians.

So the debate will continue, until there is compelling evidence that pharma's influence on CME—influence that has clearly been moderated during the last several years—has caused some undeniably beneficial or untoward healthcare outcome. 

* Arguably the height of pharma's influence on CME, before the institution of stricter firewalls between pharma marketing and CME.

Photo of the pop duo Sonny & Cher, who charted with the 1967 hit "The Beat Goes On," from Wikipedia.

Addendum: Some may cite the exuberant use of off-label fen-phen in the 1990s as an example of the adverse influence of pharma-funded CME. However, the fen-phen mess doesn't seem to be easily distilled to a single factor. Nevertheless, I am certainly receptive to any evidence that Wyeth funded CME activities in which the drug combination and supportive studies were discussed. 

At last count, the number of Americans who had contracted measles this year was 127. Now add 4 more cases.

This week, the CDC's MMWR reports a total of 131 cases of the highly contagious infection in 15 US states and the District of Columbia from January 1 to July 31 (Table). The overwhelming majority of these cases were imported* (13%) or linked to imported disease (76%). (It is important to note that the number of imported measles cases in the United States has not changed appreciably over the years, but that the number of importation-associated cases accounts for this year's dubious record.) A large percentage (81%) of measles cases were related to 7 outbreaks (≥3 cases). Fifteen individuals, including 4 children younger than 15 months, were hospitalized for disease; however, there have been no deaths—yet. 

Most important, however, is the fact that a whopping 91% of cases occurred in individuals who had not received vaccination or whose vaccination status was unknown. Among these 112 patients, 85% were eligible to receive vaccination, but 66% had declined because of "philosophical or religious beliefs." 

Location	Measles Cases
Illinois	32
New York	27
Washington state	19
Arizona	14
California	14
Wisconsin	7
Hawaii	5
Michigan	4
Arkansas	2
DC	1
Georgia	1
Louisiana	1
Missouri	1
New Mexico	1
Pennsylvania	1
Virginia	1

The MMWR highlights outbreaks in 2 locations, Washington state and Illinois, in which affected children had not been vaccinated on the basis of personal-belief exemptions. A sizable portion of these children were home schooled, which obviates the vaccination requirement for traditional-school enrollment.

In an editorial note, the CDC advises that the current national vaccination rate for measles is adequate to prevent the "sustained spread of measles," but that importation-associated outbreaks are likely to continue as long as there are geographic clusters of unvaccinated individuals. Unfortunately this information will probably be used by parents who forego vaccination to maintain their behavior.

Most affected by the deferral of measles vaccination are immunocompromised children and children younger than 12 months of age, who rely on adequate herd immunity. It appears to be a mere matter of time before a measles outbreak will cause a known, severe complication of the disease, like encephalitis or death, in the United States. Such an event has already occurred in the United Kingdom.

* Genetically or epidemiologically linked to cases in Italy, Switzerland, Belgium, India, Israel, China, Germany, Pakistan, the Philippines, and Russia.

Photo of child with measles rash from the CDC.

While sympathies for anyone with an untreatable and ultimately fatal condition—like Duchenne muscular dystrophy (DMD)—are undeniable, the right for such a person to access an experimental, proprietary therapy is not clear. There's the issue of unproven safety (not to mention efficacy) and the violation of numerous clinical-trial protocols (on which evidence-based medicine rests) that control important variables—like an enrollee's health status, the double-blind process, and randomization of treatment.

Nevertheless, a New Jersey federal judge ruled yesterday that a 16-year-old boy with DMD, Jacob Gunvalson, should have access to PTC124, a drug in clinical-phase development by PTC Therapeutics. According to PTC's web site, a phase 2b trial of the drug is being conducted in ambulatory DMD patients with a nonsense mutation. PTC124 is an orally administered, small molecule that targets this particular mutation type.

It has not been reported if Gunvalson even harbors a DMD nonsense mutation (if not, the use of PTC124 would be, well, nonsense). Also photographs in news reports suggest that the teenager, shown in a wheelchair, is not sufficiently ambulatory at his age to qualify for the PTC trial. Confirmed particulars of the case, expected to be available in the judge's forthcoming written order, should answer these and other issues* that may have implications for anyone seeking access to experimental treatments.

According to the NYT, PTC Therapeutics plans to appeal the decision, and federal regulators must still approve Gunvalson's application to use PTC124.

* For instance, will Gunvalson even be considered an enrollee in the phase 2b trial, should he receive PTC124?

The use of cardiac death (as opposed to brain death) to obtain organs for transplantation has been accepted practice for more than a decade in the United States.* According to various protocols, cardiac death in the context of organ harvesting is defined as asystole for 2 or more minutes after the withdrawal of life support. The criterion is based on the fact that autoresuscitation has not been observed after 65 seconds of asystole. However, a logical problem arises when considering the transplantation of a heart after cardiac death.

As ethicist Robert Veatch writes in this week's NEJM, it should be impossible to transplant a heart after the irreversible cessation of cardiac function. If the heart can be restarted in the graft recipient, then the donor could not have been dead in the first place on the basis of cardiac death. Moreover, the very act of removing the "restartable" heart from the donor is equivalent to killing the donor by means of organ removal. Veatch concludes that it is therefore impossible to legally harvest a heart in the setting of cardiac death and proposes 2 ways by which the paradox can be resolved.

One is to alter laws to permit heart removal from living donors. In such cases, however, strict scenarios—such as terminal illness or previous consent—would have to be explicitly defined. The other is to redefine brain death as the loss of higher cortical function (ie, consciousness), which may have popular support. Until then, Veatch argues, "[A]ny successfully transplanted heart cannot have come from a person who was declared dead on the basis of irreversible stoppage of the heart."

Veatch's editorial appears in the same NEJM issue in which Denver physicians report their experience with cardiac transplantation in 3 infant recipients following cardiac death in pediatric donors.

* Although the management of end-of-life care, especially if left to transplant surgeons, can go horribly wrong—for example, as in the case of Ruben Navarro.

Update: Further debate on the controversy of heart donation after cardiac death, particularly in the case of infants, was explored by The Washington Post. Veatch further defined the procedure as "homocide," according to the paper, but a Denver cardiologist involved in the pediatric transplantations called Veatch's assertions "fussy semantics." 

It may not have occurred to the WSJ Health Blog that surgeons throw instruments in fits of pique, but this type of behavior is nothing new to those in healthcare. Finding a medical trainee who's observed verbal or threatened physical abuse from surgeons in the OR is the act of finding a medical trainee.

For the young and relatively uninitiated, the tolerance of bad behavior from medical superiors toward nurses and other healthcare workers has been taken as a matter of course in the stiffly hierarchal world of medicine. And in some cases, the tolerance of abuse serves as a license for trainees to mirror the behavior. But this misguided tolerance is finally waning, and rightly so—even if it means losing the lucrative business of surgical specialists.

The Boston Globe reported Monday that Massachusetts hospitals, like the North Shore Medical Center and Saint Vincent Hospital, are adopting a kind of 3-strikes rule for physician outbursts, before some kind of discipline is implemented. Of course, intervention after 1 or 2 strikes should be considered by any hospital administration, depending on the behavior.

Another deterrent is to publicize the names of those who exhibit the alleged bad behavior: like orthopedic surgeon Peter J. Mulhern, who reportedly threw 2, 10-pound limb-stabilizing sand bags in the Saint Vincent OR, hitting a nurse's foot; or orthopedic surgeon Murray J. Goodman, who reportedly flung dull scissors in the North Shore OR, just missing a nurse's head.

While doctors' bad behavior may be explained (or excused) by the high-stress environment in the OR and the fact that "[s]urgeons hold patients' lives in their hands," the sand-bag incident with Mulhern occurred in the context of 2 delayed surgeries for carpal tunnel syndrome, wrote The Globe—hardly a life-in-the-balance condition.

The Globe also reported that Mulhern was suspended by Saint Vincent in 2002 and moved his practice to Fort Oglethorpe, Georgia.* Goodman is evidently still affiliated with the North Shore Medical Center in Massachusetts.

The Massachusetts hospitals' disciplinary actions are presumably in line with recommendations from the Joint Commission, which released an alert last month requiring that "all accredited hospitals create a code of conduct that defines acceptable and unacceptable behaviors and...establish a formal process for managing unacceptable behavior," beginning January 1, 2009.

* Which is sufficient punishment in my mind.

Photo of piece of surgeon's arsenal: iStockPhoto

A US biostatistician, who testified for runner Mary Decker in a 1997 doping hearing, believes that doping tests among athletes are inherently flawed. In the latest issue of Nature, Donald Berry cites a lack of validated sensitivity and specificity data for individual doping tests—data which are necessary to know the accuracy of positive tests.

Berry argues that, even when a test has a very high specificity (eg, 95%), the false-positive rate in a non-doper who provides 8 different urine samples remains remarkably high (eg, 34%).* A comparable false-positive rate would also apply to the large number of samples assayed by a particular doping laboratory. Invariably some percentage of these tests in non-dopers would turn up positive and, consequently, ruin careers. Berry concludes that doping labs "must prospectively define and publicize a standard testing procedure, including unambiguous criteria for concluding positivity...and validate that procedure in blinded experiments."

The flip side of Berry's argument, the reliability of negative doping tests, was explored recently by Danish investigators, who showed that the detection of recombinant human erythropoietin (rHuEPO) in intentionally doped volunteers was astonishingly inconsistent within and between official doping labs.

* 1 – 0.95 to the 8th power = 1 – 0.66 = 0.34.

Photo: iStockPhoto

Among the compromises reached by the Massachusetts legislature last week in its health-code bill is the stipulation that drug companies will report any physician gifts exceeding $50 to the state's Department of Public Health. The bill now awaits the signature of Governor Deval Patrick, but 5 trade groups* are attempting to persuade the governor not to sign by way of a full-page ad in The Boston Globe.

In addition, PhRMA senior vice president Ken Johnson wrote yesterday in a press release that the public disclosure of gifts "could chill ongoing clinical research in the commonwealth." Johnson proposes, "Physicians and other healthcare providers who do not want such personal information disclosed may decide to no longer work with the pharmaceutical research companies sponsoring the clinical studies." He adds, "Public disclosure of a pharmaceutical company's arrangements with the principal investigators of its clinical trials also would reveal sensitive, proprietary business information to a company's competitors. This could erode the independent decision-making of companies trying to bring science from research facilities to patient care settings."

However, it seems unlikely that Massachusetts physicians would forego pharma research grants for clinical study given 1) the nature of this particular "gift" and 2) the fact that grant information is already publicly available through the NIH database at clinicaltrials.gov (although the size of the grant, to my knowledge, is not provided).

As far as public disclosure revealing "sensitive, proprietary business information," PhRMA's Julie Corcoran tells Pharmalot that, according to the bill, companies "shall disclose...the value, nature, purpose, and particular recipient of any fee, payment, subsidy or other economic benefit"—which, she argues, is subject to overly broad interpretation. But again, in the case of clinical grants, the nature, purpose, and recipient of the funds are already available through the NIH registry.

* Biotechnology Industry Organization, Massachusetts Biotechnology Council, Associated Industries of Massachusetts, Massachusetts High Technology Council, Cambridge Chamber of Commerce, and PhRMA.

8/11 update: The Boston Globe reports that Governor Patrick signed the bill yesterday.

Good lord almighty. I'm beginning to think that the ACCME should move to Cuba.

The council that bestows accreditation on organizations to provide CME is now proposing that independent physicians or writers who are involved in the production of any kind of promotional material for pharma cannot be involved in the development of content for CME. This would arguably prohibit any non-industry physician involved on a company's advisory board or speakers' bureau from participating in the production and delivery of CME. Likewise, any independent writer who produces promotional material for a company could not be involved in the creation of CME content about the same drug class. Yeesh, what's next, ACCME? Little Mao caps?

The ACCME's new proposal is evidently based on the following:

In May 2008, the Attorney's[sic] General of thirty US states won a judgment against a commercial interest that included the stipulation that a promotional speaker for the commercial interest could not also be a CME speaker, on the same class of drugs discussed in the promotion activity, in a CME activity that received funding from the commercial interest.

As Thomas Sullivan at the Policy and Medicine blog points out, the ACCME's characterization is not exactly accurate. In May 2008, Merck actually agreed to a multistate* settlement (it was not a judgment) regarding its Vioxx ads. With respect to the funding of CME, the settlement indicated that Merck will comply with the ACCME's Standards of Commercial Support (nothing particularly earth-shattering) and that any person acting in a promotional capacity for Merck shall disclose to CME participants this promotional relationship (again, nothing particularly earth-shattering). This settlement also indicated that Merck cannot fund a CME program, if it has foreknowledge that a CME speaker has been a promotional speaker for Merck during the last 12 months (a minor tremor, given that Merck could not recommend CME speakers anyway, according to the ACCME standards).

In addition, the ACCME cites a June report from the AAMC Task Force, which urged academic medical centers to discourage their faculty from participating in industry-sponsored speakers' bureaus. But the Task Force also wrote,

To the extent that academic medical centers choose to allow participation of their faculty and staff in industry-sponsored, FDA-regulated programs, they should develop standards that define appropriate and acceptable involvement.

1. Academic medical centers should require full transparency and disclosure by their personnel to the centers and when participating in such programs; and

2. Academic medical centers should require that payments to academic personnel be only at fair market value.

So the ACCME, given the full details of the Merck settlement and the AAMC opinion, is overgeneralizing and grossly overstepping its purview, IMO, by proposing that non-industry physicians limit their communication to other physicians, depending on the setting. Moreover, the ACCME's proposal would needlessly undermine opportunities for independent medical writers to earn a living.

Or to provide another free-speech comment: Blpppht.

AAMC = Association of American Medical Colleges; ACCME = Accreditation Council for Continuing Medical Education.

* Twenty-nine states and Washington, DC.

While we wait for confirmation and further explanation from the scientific community (and I suspect specifically from Northern Arizona University's Paul Keim) about the forensic evidence that ties Bruce Ivins to the 2001 anthrax attacks, we can comb the documents released today by the DoJ. At least from my perspective, the evidence against Ivins is very compelling.

Among the presented information is the fact that the Ames strain of Bacillus anthracis contained in the mailed letters can be directly linked to a single spore batch, called RMR-1029. This identification was accomplished by the detection of 4 characteristic genetic mutations, which are otherwise not described in the DoJ documents; however, it is possible that these mutations refer to the use of highly mutable single nucleotide repeat (SNR) markers described in a previous post here on the subject.

Of the 16 domestic labs that had RMR-1029 before the 2001 anthrax attacks, only one—the USAMRID facility in Fort Detrick, MD—was located where the identified "federal eagle" envelopes used in the attacks were distributed and sold (Maryland or Virginia).

At Fort Detrick, RMR-1029 was stored in the B3 biocontainment suite in Building 1425, to which Bruce Ivins had "unrestricted access." Moreover, Ivins had been "the sole custodian of RMR-1029 since it was first grown in 1997."

Because the B. anthracis spores in the letters sent to the Post and Tom Brokaw (postmarked 9/18/2001) were physically different* from those contained in the letters to Senators Leahy and Daschle (postmarked 10/9/2001), the investigators concluded that the spore batches were created from the RMR-1029 flask at Fort Detrick on two separate occasions. This conclusion is supported by the presence of a B. subtilis contaminant in the Post/Brokaw letters, which could not have been derived from the Fort Detrick flask.

On the basis of nighttime work records at Fort Detrick, the DoJ proposes that Ivins produced the Post/Brokaw B. anthracis during September 14-16 and the Leahy/Daschle spores sometime from September 28 to October 5. It is important to note that Ivins worked alone during these late-shift periods, and that his work time differed considerably from those of other Fort Detrick researchers with access to RMR-1029.

Probably most damning is the allegation that Ivins stalled the genetic identification of the RMR-1029 batch at Fort Detrick by submitting possibly sabotaged or false samples to the FBI for analysis. Initial samples provided by Ivins in 2002 were unusable, according to the DoJ documents, and a second sample of RMR-1029 from Fort Detrick did not contain the characteristic 4 mutations. In 2004, the FBI seized the RMR-1029 flask, which subsequently indicated a genetic match to the B. anthracis contained in the letters. 

A final note of curiosity is the return address provided on the Senators' letters: "4th Grade, Greendale School, Franklin Park, NJ, 08852." Former person of interest Stephen Hatfill had been loosely linked to the fictitious address, owing to erroneous media reports that he lived near a "Greendale Elementary School" while in Zimbabwe. The DoJ documents suggest that the return address may be an indirect reference to the Greendale Baptist Academy in Wisconsin and a related suit filed by the ultra-conservative American Family Association against the Wisconsin Department of Public Services, which was investigating the corporal punishment of a 4th-grade student at the Academy. The DoJ notes that "Mr. and Mrs. Bruce Ivins," who were practicing Catholics, made several donations over the years to the AFA and received the organization's newsletter, which would have referenced the suit.

* Genomic sequencing, however, revealed that the B. anthracis spores in all 4 letters were identical.

Scanning electron micrograph of spores of Ames strain of B. anthracis from CDC/Janice Haney Carr.

Yesterday, the Massachusetts House and Senate reached anticipated compromises on a widely discussed pharma-code bill, reports the Boston Globe. The drafted bill, which is expected to be approved and sent to the state governor this weekend, now requires the following:

1. Companies will report any physician gifts exceeding $50 to the state's Department of Public Health, and the DPH should post this information online for public access.
2. The DPH will adopt something like the recently unveiled, voluntary PhRMA code, which bans branded trinkets and out-of-office meals with reps.
3. A $5000 fine will be levied for each violation by pharma or medical-device companies.