TortsProf Blog

Ghostwriting of Medical Studies

The New York Times examines the practice of ghost-writing medical research studies that are subsequently published in medical journals such as JAMA:

The drug maker Merck drafted dozens of research studies for a best-selling drug, then lined up prestigious doctors to put their names on the reports before publication, according to an article to be published Wednesday in a leading medical journal.

....

The lead author of Wednesday’s article, Dr. Joseph S. Ross of the Mount Sinai School of Medicine in New York, said a close look at the Merck documents raised broad questions about the validity of much of the drug industry’s published research, because the ghostwriting practice appears to be widespread.   “It almost calls into question all legitimate research that’s been conducted by the pharmaceutical industry with the academic physician,” Dr. Ross said, whose article, written with colleagues, was published Wednesday in JAMA, the journal of the American Medical Assocation.

Merck on Tuesday acknowledged that is sometimes hires outside medical writers to draft research reports before handing them over to the doctors whose names eventually appear on the publication. But the company disputed the article’s conclusion that the authors do little of the actual research or analysis.

And at least one of the doctors whose published research was questioned in Wednesday’s article, Dr. Steven H. Ferris, a New York University psychiatry professor, said the notion that the article bearing his name was ghostwritten was “simply false.” He said it was “egregious” that Dr. Ross and his colleagues had done no research besides mining the Merck documents and reading the published medical journal articles.

The JAMA article discussed by the Time is available here.  This article certainly adds fuel to the peer review discovery controversy, which Bill has both written about and discussed here and here. 

(Via MassTortsProf).   

- SBS 

 

Chronicle of Higher Education on Peer Review Discovery

The Chronicle of Higher Education has a story (link will explode in five days), quoting me, about Pfizer's efforts to obtain discovery into the peer review process.  It is a better story than most, in my view, in terms of recognizing the potentially overblown (but not baseless) predictions of doom raised by journal editors.  As the story notes, but just to be sure it's clear, I have done work for pharma companies, though not Pfizer.

--BC

Peer Review & Discovery

I'm traveling (and writing this in a dark hotel room with the rest of my family asleep, so forgive incoherence), and so haven't been following it all carefully, but In The Pipeline notes, in connection with Pfizer's efforts to take discovery into the peer review process at the NEJM, some developments.

A fair amount of commentary has suggested that Pfizer is purely fishing and/or purely an attempt to scare reviewers off. Perhaps, but it's worth remembering (as I argue here (e-mail me for a final reprint)) that much of what happens in the peer review process can be quite relevant to litigation (tending to lead to admissible evidence) -- and peer reviewers, and journals, are just as much subject to discovery as, say, doctors' records.

This is all the more so if the methodology used in the article is at issue in the litigation, in which case the mere fact of peer review makes testimony based on that methodology more likely to be admitted under Daubert. All of the Daubert factors are fact issues; thus, discovery related to them is appropriate. (If the peer review is done poorly and the peer reviewers' notes indicate that, then that factor should get less weight, for instance.) After losing the first subpoena issued, Pfizer has narrowed its request in a way that suggests to me that they are in fact focused on Daubert issues, as they are just asking for peer reviewers' comments.

All that said, as again I argue, there are in some cases greater risks in connection with peer review discovery than garden-variety third party discovery, and I propose some protections. But I do not think it appropriate to treat the entire neighborhood of peer review as sacrosanct and immune from the same third-party discovery that the rest of us are subject to. The courts are looking at the requests and, probably appropriately, balancing the hassle compared to Pfizer's interests. Maybe these requests should be granted, maybe they shouldn't, but the outrage seems misplaced.

--BC

Peer Review Discovery in Bextra/Celebrex Litigation

Pharmalot has the editorial from Science. For a view on the other side (i.e., not panicked at the prospect of discovery into peer review), see my Nebraska Law Review article from last year. The SSRN draft is here; feel free to send me an e-mail to get a reprint.

--BC

Litigation Science

Science News Online has an overview of some recent work on the subject of litigation-driven science that was presented at a 2006 Coronado Conference (presented by SKAPP at George Washington) and recently published.  Many of the conclusions echo mine in this piece published in the Nebraska Law Review.

--BC

Big Win for Pfizer in Celebrex Litigation

Pharmalot has the details and the order (in Word form, with metadata indicating it originated from plaintiffs' firm Lieff Cabraser) finding no Daubert-worthy evidence of causation at the most common dose of 200 mg.  You can also get the order in PDF form here: Download CelebrexDaubert.pdf.

See also the Reuters story.

--BC

(I have done some work in the Cox-2 litigation, but none in the Celebrex case and none of any sort for Pfizer.)

Litigation-Driven Science, Nth Part

Environmental Health & Perspectives has posted the current drafts of a number of articles addressing litigation-driven scholarship.  If you find the pieces interesting, feel free to get in touch for a reprint of my Nebraska piece covering many of the same issues from a bit more of a litigation perspective.  I end up in roughly the same place as most of the writers there seem to -- that is, there's nothing specifically about litigation-driven work that should scare us any more than other science with potential biases.

--BC

Gottstein Still in Talks

Jim Gottstein -- the Alaska lawyer who subpoenaed Zyprexa documents from David Egilman -- appeared on the law radio show I do on a local community station today.  I do not yet have the archive uploaded, but we mostly discussed his organization and its work to prevent forced medication.  We did briefly discuss the issued relating to the document leaks, and he stated that he continues to be in discussions relating to settlement and that he is optimistic that a settlement will be reached.

--BC

Beck & Herrmann on my article

A well thought-out post addressing my recent Nebraska Law Review article is here, providing a practitioner's reaction.  (I still have reprints if anyone wants one.)

As a preliminary note, it may be worth noting that I'm only a few years out from active practice and (as I occasionally note) maintain a small consulting practice, largely expert-oriented, so I'm not actually unaware of the realities.

They have three general reactions:

1. They point out that two-bit clowns can get published in peer reviewed journals.  Indeed they can; I think allowing some level of discovery into the peer review process will help clarify that the fact of peer review does not constitute a guarantee of quality, thus perhaps mitigating the harm of this fact.  I certainly don't think anything I suggest would exacerbate the practice. 
   
   They also note that "litigation-driven scholarship" is much broader than well-credentialed people, and that's absolutely true too.  My primary example comes from a well-credentialed scholar, but I don't mean to suggest that there's not a whole lot of quackery out there.
   
2. Work done by non-testifying experts can be hidden from view forever; pharma research that isn't published is still discoverable.  True, and a relevant point.
   
3. Nobody knows how much work done by retained plaintiffs' experts doesn't work out -- i.e., how many times the studies fail.  Beck & Herrmann note that it'd be interesting to find out the answer to that empirical question.  Indeed it would.

--BC

Gottstein's Appeal Withdrawn (Without Prejudice)

I missed this the first time around, but the Second Circuit docket reflects (and James Gottstein has posted (click on the "Zyprexa Papers" link)) that, last month, contemporaneously with David Egilman's settlement with Lilly, Mr. Gottstein has withdrawn (without prejudice) his appeal from Judge Weinstein's order, presumably to continue settlement discussions.

The document is here: Download 20070907WithdrawAppeals.pdf.

--BC

Egilman Speaks

David Egilman has posted a comment at Pharmalot.  He says he released all of the documents "he had" (which does not state whether he previously had more documents or requested other documents), that he did not admit to anything illegal (see my earlier post), and that, while he recognizes that Lilly has a different story, he does not believe that story.

--BC

"It depends on what the meaning of the word 'illegal' is"

Just to tie up a loose thread from yesterday's news about David Egilman settling with Lilly...

In Pharmalot's first story breaking the news, this comment was reported:

However, Egilman’s attorney, Alex Reinert says that Egilman didn’t admit to anything illegal. A quick read indicates he appears to be correct (although we recognize that other interpretations are possible).

(Update: I hadn't realized until just now that Reinert is evidently a lawprof, though he's also still listed on a firm website.  He's also a graduate of Brown, where Egilman is a professor.)

And in the WSJ Health Blog post, there's a similar comment, plus a discussion of what else Egilman admitted to in his affidavit:

Alexander Reinert, a lawyer representing David Egilman, the expert who settled with Lilly, tells the Health Blog that the company mischaracterized his client’s signed statement. Egilman never admitted doing anything illegal and didn’t cherry-pick documents to send the Times. “Lilly has an interpretation we don’t believe is accurate,” Reinert says. While Egilman admitted to violating a protective order, “that’s not saying he did something illegal,” Reinert says.

First, on the question of whether he admitted to doing something illegal, I suppose it depends on what counts as illegal.  I generally think of federal court orders as having the force of law, being, you know, oh, what's that phrase?  Oh, right -- the basis for the rule of law.  Here, Egilman unambiguously admitted [PDF] under oath to violating the protective order duly issued by a federal judge ("I violated Case Management Order No. 3 ('CMO-3'), which is in force in the Zyprexa MDL.").

The CMO (2004 WL 3520247; also available in a big PDF here: Download CMO3.pdf) provides in the endorsement certain acknowledgments about the force of signing.  You can see Egilman's signed endorsement here: Download cmo_endorsement_egilman.pdf.  In that document, Egilman agreed:

I further agree and attest to my understanding that, if I fail to abide by the terms of the Order, I may be subject to sanctions, including contempt of court, for such failure.  I agree to be subject to the jurisdiction of the United States District Court, Eastern District of New York, for the purposes of any proceedings relating to enforcement of the Order.

So he's acknowledged (again under oath) that violation of the Order can result in sanctions, including contempt.  This is, of course, not surprising, but bolsters the idea that violation of the order is illegal.

Black's defines "illegal" in a pretty straightforward way: "illegal, adj. Forbidden by law; unlawful."  By that or any ordinary meaning of the term "illegal," it seems to me that admitting violation of a court order (remember: court orders = force of law) constitutes admitting an illegal action.  (Added: This is consistent with Judge Weinstein's repeated use of the terms "illegal," "stolen," and "conspiracy" in his order, incidentally.)

And even if one were to limit the term to only include acts that are clearly criminal, recall that Egilman was at least concerned enough about potential criminal liability to invoke the Fifth Amendment right against self-incrimination, something he expressly acknowledges again in the affidavit. (See also this post.)  That said, if "illegal" is in fact defined in such a constrained way as to only include clearly criminal conduct, it would be at least semi-credible to say that he didn't admit to acting illegally.

As for the second argument -- that he didn't admit to cherry-picking documents -- that seems plainly contradicted by the affidavit itself, which is worth excerpting at some length:

That seems to be at odds with his attorney's statement: "Reinert says that’s not the same as cherry-picking: 'He knew there were other documents but he didn’t have them.'"  Note that Egilman says  in his affidavit that he reviewed documents and released a set of documents -- i.e., not all of what he had reviewed.  Even if he no longer had them at hand, he undoubtedly could have obtained them; to call what he did anything other than cherrypicking would seem to give cherrypickers an unusual definition, to say the least.

--BC (who, as noted repeatedly before, does some consulting work for companies who are or have been adverse to parties for whom Egilman has served as an expert witness, but not including Lilly)

Updated: Egilman "Accepts Responsibility," Settles with Lilly for $100K

Pharmalot broke the story of David Egilman settling his part of the document leak with Lilly to the tune of $100,000 (to be donated to charity).  The stipulation is available here: Download EgilmanSettlement.pdf, and his affidavit is here: Download EgilmanAffidavit.pdf.  (You will note that it indicates that it is page 1 of 80; I am not posting pages 2 through 80, as they are simply Judge Weinstein's order.)

The affidavit is short; in it, Egilman explicitly acknowledges that he released documents that would help the plaintiffs and that there was an alternative perspective he intentionally avoided providing:

Given number 5, this comment from Egilman's attorney (to Pharmalot) is intriguing at least:

However, Egilman’s attorney, Alex Reinert says that Egilman didn’t admit to anything illegal.

Violation of a federal case management order is not necessarily criminal, and in that (narrow) sense, I suppose it's not the admission to "anything illegal," but he explicitly acknowledges violating a court order.

It appears that James Gottstein (the Alaska lawyer who subpoenaed the documents from Egilman and provided them to media) is still in the mix, though I'm still digging through the filings.

Update: Gottstein has changed counsel, dropping Bracewell & Giuliani and adding in Berkman, Henoch, Peterson & Peddy.  Filing here: Download GottsteinSub.pdf

Updated again: I've now looked through the dockets of both the district and circuit courts and see nothing that indicates definitively that any of the other parties have settled.  That leaves not just Mr. Gottstein but many of the enjoined entities.

Yet another (minor) update: In case you're new to the site and want some background, I've done a number of posts about Zyprexa, most about the document dispute; they're here.  Also, I forgot to mention initially that I perform a small amount of consulting for pharmaceutical clients.  Lilly is not one of my clients (nor has it been in the past), but I am involved in litigation in which Egilman is or was an expert for plaintiffs.

And another one: Welcome, WSJ Health Blog readers.  If others haven't seen the post there, do so; it's a good one.  I'm hoping to get a bit more up about the case this weekend.

--BC

O'Quinn Arbitration Ruling

Overlawyered has the O'Quinn arbitration ruling [PDF].  The whole thing is worth reading as it addresses the significant challenges in the management of funds in mass tort litigation.

In particular, it's got a fascinating discussion of O'Quinn's use of client funds to pay for what is referred to as "the Baylor study," though it's not actually associated with Baylor.  As the (partial) dissent puts it:

O'Quinn fashioned the funding of a Baylor Medical Study in somewhat less than a straightforward manner.  [Several industry studies suggested no causation.]  O'Quinn set out to fund a study to counteract these medical study findings. . . .

The name "CAPS" is found in the article as the entity funding the Baylor study.  CAPS is an acronym for a group in support of the "women" in their battles with the manufacturers.  [Ed. note: not sure why the scare quotes are there around "women."]  O'Quinn used client money to fund the Baylor study through donations to CAPS.  The method of funding is as follows:

O'Quinn would cut a check from the General Expense Fund to a designated breast implant client.  The client would then send a check out of the client's account to CAPS.  CAPS would in turn send the money to the Baylor study group.  Medical studies ethics require that a statement of disclosure be made in every medical article or study as to who the individuals and/or entities are that are funding the study.  This study at Baylor, funded in this deceptive way, nowhere states the study was being funded by plaintiffs' lawyers or O'Quinn.  This was a deceptive practice involving clients' money.  The clients were personally involved in the misrepresentation of the true funding of the Baylor study.

O'Quinn's business accountant testified that the method of funding was a "subterfuge."

Yet another consequence of Daubert and, I suppose, the more general desire to avoid bias challenges, and perhaps another reason to permit (and pursue) some discovery into the publication of relevant scholarship.

--BC

Expanding Information About Experts

Interesting new piece (out now in the Nebraska Law Review) available on SSRN.  In it, Stephen Easton (Missouri-Columbia) argues for broader information to be shared with juries about experts -- how the sausage is made, so to speak.  The more formal abstract:

Now that more than a decade has passed since the U.S. Supreme Court's decision in Daubert v. Merrell Dow Pharmaceuticals, Inc., 509 U.S. 579 (1993), it has become clear that the decision, though certainly important, was not quite the panacea for faulty expert testimony that many of us first thought it would be. As the first part of this article notes, even after Daubert, which directed trial courts to take seriously a party's motion to exclude faulty expert testimony, there are still many instances where experts testify to incorrect opinions. This article observes that, in each case where opposing experts testify to directly opposite opinions about an issue of historical fact, one of the experts must be wrong. It argues that, in any case of opposing expert testimony, we expect the jury to determine which of the experts is wrong, so we should give the jury as much information as reasonably possible to help it determine which expert is wrong and which is right. This article recommends that courts end their tendency to give expert witnesses preferred treatment, as vis-a-vis fact witnesses, under civil procedure (discovery), professional responsibility, and evidence law. Given the substantial potential for retaining attorneys to influence the testimony of their expert witnesses, courts should provide the jurors who must evaluate the resultant testimony with at least as much information about the formation of expert testimony as they do about the formation of fact witness testimony. To give the jurors the information they need to sift the wheat from the chaff in expert testimony, courts in civil cases should: (a) permit attorneys to contact opposing retained expert witnesses ex parte; (b) require disclosure and discovery regarding all communications between attorneys and the expert witnesses they retain; (c) provide for automatic disclosure of all drafts of expert witness reports that have exchanged hands between experts and the attorneys who retained them; (d) allow a party to introduce the testimony of any person designated as an expert by any party; and (e) admit bias testimony about the original retention of the expert by a party other than the one calling the expert at trial, when that is the case. By adopting each of these recommendations, courts would treat experts as they do fact witnesses and thereby give jurors the same sorts of information about the formation of expert testimony, including the influence of attorneys on that testimony, that they receive about the formation of fact witness testimony.

--BC

Egilman, Gottstein Settling with Lilly Regarding Zyprexa Document Leak?

That's suggested by a pleading filed back in May: Download 20070529_extension.pdf

It appears that Egilman was at that time very close to a settlement, while Gottstein was awaiting the resolution of those talks.

(In case you're just joining the story, David Egilman was an expert for plaintiffs in the Zyprexa litigation.  In cooperation with Alex Berenson of the NYT, he was subpoenaed by James Gottstein, an Alaska lawyer advocating against forced psychiatric medications.  The documents were widely distributed; Judge Weinstein concluded that their distribution violated his protective order and enjoined some parties from further distribution and made noises about contempt.  Go here for many more posts.  My article about it continues to muddle along.)

--BC

Shameless Self-Promotion: Law & Science at DRI

With Robert Scott, I will be presenting at this October's Annual Meeting of the Defense Research Institute.  The ludicrously large PDF of the program is here. Our subject:

The Intersection of Law and Science—The Unintended Consequences of Judicial Standards for Expert Evidence

Presented by the Toxic Torts and Environmental Law Committee

This presentation will address several unexpected results of the Daubert decision and other standards for scientific evidence. It will include a discussion of scientific studies or literature created for litigation, recent attacks in “scientific” literature on industry and
industry-funded studies and self-proclaimed “public interest” groups with ties to litigation. The presentation will also include a discussion of discovery regarding this type of litigation-related science as well as the potential and propriety of bringing discovery into the peer review process. Finally, the use of historians and historical context evidence in mass tort litigation will be explored.

"End the Censorship of Science"

An interesting column from The Scientist on the confidentiality of peer review and other materials.  The conclusion:

So what possible benefit can confidentiality serve? Who is being protected from what? One editor who responded to my e-mail replied that “review processes everywhere benefit from candor, and abundant experience tells us that without confidentiality evaluators are likely to be less candid.”

If this is true, it can be accommodated by instituting a period of confidentiality for manuscript files. Here’s my proposal: Science journals open their files to reasonable requests after a five-year interval. Just as government files are made public – in the United Kingdom after a 30-year lag, in the United States after 25, according to change late last year – this would be a powerful contribution to an open society. It will get to the heart of how research is done and how human relationships govern science. And it will be a goldmine for science history studies, which are not given nearly enough credence.

I’d love a couple of months’ sabbatical poking around in the dusty storerooms of the major journals, wouldn’t you?

FDA Investigating Zyprexa Data

The NYT story has more. 

The story is written by Alex Berenson, described by Judge Weinstein as "conspiring" to improperly release documents in the litigation.  Berenson describes the document leak as such:

The document from 2000 and others were provided to The Times by James Gottstein, a lawyer who represents mentally ill people he says are forced to take psychiatric medications against their will.

Law & Science & Shameless Self-Promotion

My Nebraska Law Review piece is now out: The Overlapping Magisteria of Law and Science: When Litigation and Science Collide, 85 NEB. L. REV. 643 (2007).  I don't have hard copies yet, but it's up at both Westlaw and Lexis; if you're interested in a reprint, send me an e-mail and I'll try to get one to you.  The abstract (which does not appear in the journal):

The Supreme Court’s 1993 decision in Daubert v. Merrell Dow Pharmaceuticals transformed courts’ evaluation of expert testimony.  Many courts, applying Daubert, focus extensively on whether the purported expert’s methodology has been published in a peer-reviewed journal.

This focus on peer review results in two unintended consequences that have triggered criticism: litigation-driven scholarship and litigants taking discovery into the peer review process.  Critics contend that litigation-driven scholarship is irredeemably biased and that peer review discovery is too often an effort to intimidate scholars from speaking on subjects of public concern.

In this Article, I explore these phenomena and the criticisms of them, as well as the history of peer review itself.  Contrary to the critics, I ultimately conclude that each, in fact, can strengthen both law and science through cross-fertilization, if appropriate checks are established.  Such efforts will better reflect law and science’s overlapping magisteria (a term roughly meaning the disciplines’ area of authority).  A better recognition and understanding of this overlap will create incentives to improve both law and science.

Letter: Litigation and Research

A while back, I posted about a dispute regarding the impact of litigation on research, in particular in the context of the neurological effects of welding rods.  One of the attorneys involved (who was involved in the correspondence in Neurology, sent the following.  As I noted in the previous post (and consistent with my article linked to in that post), I generally think the dangers of such discovery are overstated.

Dear Professor Childs:

You recently called your readers’ attention to a publication by Dr. Brad Racette, entitled "The impact of litigation on neurologic research," published in 67 Neurology 2124 (2006). Dr. Racette, along with his legal counsel, decries the untoward effect of litigation on research generally, and on his research specifically. As you noted, Dr. Racette, along with his co-authors and legal counsel, and I engaged in a further exchange of views in the Correspondence section of Neurology, but the 400-word limit on letters to the editor prevented a full exploration of the issues. Dr. Racette’s response suggests that the federal court ruled that the subpoena prosecuted was over broad and burdensome. Most readers will discern the obvious equivocation in that a quashed subpoena would have placed no burden upon Dr. Racette. To the contrary, the subpoena at issue was served with a proposed protective order and an invitation to discuss how the subpoena and the order might be modified to protect legitimate interests. Those invitations were rebuffed, and the Court ultimate enforced the subpoena in large part; hence Dr. Racette’s belated special pleading in the official journal of the American Academy of Neurology.

Indeed, there is much more I could say about Dr. Racette’s activities in conducting the screenings of Alabama workers, which "medico-legal" activities gave rise to his published papers. See Racette, et al., Prevalence of parkinsonism and relationship to exposure in a large sample of Alabama welders," 64 Neurology 230 (2005); Racette, et al., "A rapid method for mass screening for parkinsonism," 27 Neurotoxicology 357 (2006). Unfortunately, a cloak of secrecy has been imposed, in the form of Court-imposed protective orders, and I am not at liberty to share all that I know with people who have not signed a mandated non-disclosure affidavit.

It might be helpful, however, to restate why the discovery provisions of state and federal rules of civil procedure are needed at all in the context of scientific studies, whether or not the studies enjoyed sponsorship by parties to litigation. After all, scientific studies are interpretations of analyses, often statistical, of data, which in turn represent multiple levels of hearsay. Consider a typical epidemiologic study. Patients give self-reports of symptoms. Physicians evaluate signs. Diagnostic tests are conducted, and their results reported and interpreted. Consultations may be sought. Diagnoses may be reached, and conveyed to patients, who in turn self-report their medical histories to subsequent treating physicians. Opportunities for error and systematic bias exist at every stage of the process of collecting diagnostic information and attempting to relate it to occupational, environmental, pharmaceutical,  or lifestyle exposures.

In our legal system, expert witnesses are generally permitted to hold forth with their opinions, based upon studies they did not conduct. Moreover, expert witnesses need not even be able to describe and vouch for the reliability of the many steps involved in conducting the studies upon which they rely. All they need do is accredit the study as one that they believe experts in their field would reasonably rely upon, and they are then permitted to build upon, and draw inferences from, the multi-layered hearsay study as though it were a proven fact. Typically, the expert witness tries to accredit the study by virtue of the authors’ reputations, the journal’s prestige, the claimed rigor of the peer-review process, and the lack of challenge to the study in the scientific literature. This method of accrediting studies can be highly effective in front of unsophisticated judges and jurors, who do not appreciate the severe limitations in the peer-review process. At best, all these lines of accreditation are weak, indirect proxies for the truth.

As the coat of arms of the Royal Society proclaims: "Nullius in verba." See http://www.royalsoc.ac.uk/page.asp?id=6186 <visited on April 14, 2007>. Or as the late President Reagan said in folksier style: "Trust but verify." The Korean cloning scandal, cold fusion, and other painful examples illustrate that scientists do an imperfect job of policing their community and their journals. Maybe the truth prevails in the fullness of time, but time is not a luxury that a litigant, plaintiff or defendant, caught in the jaws of the U.S. mass tort system, enjoys.

The example of the Hemorrhagic Stroke Project ("HSP"; also known as the Yale Stroke Study) is illustrative of how a study, with all the indicia of reliability, can go badly astray. Because of continuing concern over a possible relationship between the use of medications containing phenylpropanolamine ("PPA"), the FDA suggested that the manufacturers sponsor study to look for an association between recent use of PPA and hemorrhagic stroke. The manufacturers complied, and the sponsored a study, which enjoyed an independent scientific advisory board and FDA oversight. The manufacturers had no control over the conduct of the study, and the investigators retained scientific and editorial control over the work.

The HSP was a multi-centered case-control study that looked for hemorrhagic strokes in persons within an age range, and then examined whether any of them had used PPA-contained medications within a specified time frame of the onset of the stroke. The principal investigators of the HSP were highly accomplished scientists, but most of the work was done by their juniors, eager to establish themselves in tenured faculty positions. Notwithstanding the prestige of the principal investigators, the university (Yale) where the analysis was done, the oversight of disinterested scientists, open presentation of the results to an FDA Advisory Committee, the study was flawed by errors that led directly to the finding and reporting of an association in the paper, which was a featured publication in the New England Journal of Medicine. When the defendants in the PPA litigation sought discovery into the underlying data, plaintiffs’ counsel ridiculed the defendants’ efforts to discredit the "industry’s own study." Although plaintiffs were able to get past reliability challenges in federal Multidistrict Litigation, the problems with the HSP proved well-nigh insurmountable – defendants won virtually all the cases tried to verdict in the PPA litigation. After one of the first defense wins, plaintiffs sought a new trial on grounds that they were prejudiced by the extent to which the defendant attacked the validity of the HSP. At oral argument, the trial judge, Hon. Anthony J. Mohr, rejected this challenge and expressed his own skepticism about the integrity of the HSP. See, e.g., O’Neill v. Novartis Conumer Healthcare, Superior Court for California, County of Los Angeles, Transcript of Post-Trial Hearing at 47 (Mar. 18, 2004)("Yale gets a black eye"),  aff’d, ___Cal. Rptr. 3d ___, 2007 WL 586606 (Feb. 27, 2007).

The skepticism about a study such as the HSP is likely to be heightened when the study had been sponsored by an interested stakeholder. It is not only industry that has sponsored studies designed to be brought to bear on public health policy issues. Organized labor has frequently sponsored such studies, as evidenced by the collaboration between the asbestos insulators’ union and the late Irving Selikoff. More recently, plaintiffs’ counsel have directly and indirectly sponsored studies with the goal of deploying them in litigation. Several blatantly fraudulent studies, funded by plaintiffs’ counsel or by plaintiffs’ support groups, for the silicone gel breast implant litigation, helped fuel the celebrated Daubert exclusions in that litigation. The fraudulent and unreliable nature of many of the silicone studies would not have been detected if not for the subpoena-supported inquiry into the underlying data of the questionable studies.

In both science and law, studies can not be properly explored for reliability without full access to the underlying methods and data. Most journals impose severe page limitations, which prevents the sort of openness of access to data, called for by the National Academies of Science and the National Institutes for Health. Some journals now require that underlying data be submitted upon acceptance for peer review or for publication. Some of the more methodologically savvy journals have even started to make important aspects of the study, such as questionnaires and raw data sets, available as supplemental content on their websites.

Perhaps I should take solace from the following observation.  Although Dr. Racette’s work in Alabama was sponsored by plaintiffs’ counsel, plaintiffs’ counsel themselves have rejected the strictures called for by Dr. Racette. In the litigation over alleged neurologic effects of welding fume exposure, plaintiffs’ counsel aggressively have sought the data underlying studies sponsored by defendants. Dr. Racette’s public relations efforts took his special pleading to the pages of Business Week, where he complained about having to sit for three depositions.  See Arnst, "Keeping Lawyers Out of the Lab," Business Week (Feb. 5, 2007). (All these depositions involved the treatment and care of specific patients, and they were in no way different from what treating physicians routinely encounter. Inquiries into the research sponsored by plaintiffs’ counsel was deemed off limits by Dr. Racette’s counsel.) I have to say that I agree with the spokesperson for the American Association for Justice, née ATLA, who was quoted in this Business Week article as not being moved by Dr. Racette’s lament. Prohibitions against the discovery of underlying data can serve only to perpetuate the false allure of scientific infallibility, while denying litigants the right to confront and cross-examine the crucial expert witness opinion testimony that is built upon the shaky foundations of poorly conducted research. We should reject the proposal to create a privilege or a barrier that would deny litigants access to the crucial determinants of the validity of the evidence offered against them.

Nathan Schachtman

McCarter & English, LLP

Philadelphia, PA

N.B. The views expressed above are my own personal views, and not necessarily shared by my firm or my clients. I think it is likely obvious, but I will say it anyway: I have typically represented defendants in product liability cases, and I have been on both sides of demands for underlying study data.

Discovery into Research

My Nebraska Law Review piece (which should be out any day now, honest) addresses discovery into peer review, exploring a case related to vinyl chloride litigation.  There's been another recent confrontation about the issue relating to welding rod litigation, with an article (subscription only for full text) written by researchers who had performed work for plaintiffs criticizing the potential for litigation to interfere with research.

One of the defense lawyers involved has responded (with a reply from the researchers below it).  For the reasons I present in my article, I generally think the discovery sounds reasonable.  (An earlyish draft is here.)

FDA to Limit Financial Conflicts

Pharmalot has a summary.

Hilden on Zyprexa

Julie Hilden has posted a Writ column on the Zyprexa document leak.  She comes out essentially where I do on the propriety of the conduct of the parties involved -- suggesting that they should have tried the legal methods first.  I think without making that effort, any attempt to argue that the leakers were engaging in civil disobedience is silly.

She raises reasonable questions about the value of the protective order in mass torts in the first place, which, as I've noted before (and will address in an in-progress law review article) really depends on how much you consider the litigation system to be a mechanism for public information distribution as opposed to the resolution of private disputes.  I think people can reasonably come down on either side on that issue; I would prefer that the information-forcing take place through regulatory means rather than litigation, which is an extremely imprecise tool for such things, but then again, there's plenty of reasons to doubt the FDA's ability to do information forcing well, at least today's FDA.

And she also assumes something that I still haven't seen to be clearly true -- that the documents in fact provide reliable information that was not available before.  (I still have not reviewed the actual documents.)  Most of the coverage suggests that the documents have all sorts of unpleasant behavior by employees (including most likely improper off-label marketing), but I haven't seen the sort of thing that actual physicians would want to rely upon in making prescribing decisions.  Nor have I seen anything that indicates that the leaked documents contained, for instance, data that should have been given to the FDA but was not.  I'm open to being wrong on both counts -- and will be reviewing the documents for the article -- but it's not self-evident at this point.

Regardless, it's worth a read.

(Apologies for incoherence - it's my daughter's spring break and her friend's here, so there's more noise than usual...)

Appeals in the Zyprexa Documents Matter

Alaska lawyer Jim Gottstein and plaintiffs' expert David Egilman have both filed their notices of appeal from Judge Weinstein's order.  Of note, Gottstein has now apparently retained Bracewell & Giuliani (Download 3-13-07NoticeofAppeal.pdf); he was previously represented by an attorney in Alaska.

Potential Bias in Outsourced Risk Assessment

The LA Times has the story of a regulatory agency tasked with evaluating human risks of various chemicals outsourcing that work to Sciences International.  One potential problem: Sciences International has extensive work with industry, including entities with products regulated by the agency.

Lots of on-the-one-hand and on-the-other-hand in the story, and it's worth reading all the way through.

Zyprexa: Pennsylvania Sues and Thoughts on Sequestered Science

David Michaels (GWU) has a useful post noting the Pennsylvania suit (Bloomberg story) against Lilly and others for allegedly fraudulent marketing of Zyprexa and other anti-psychotic medications.  The basis for such suits, as I understand them, is the excess payments made by states through the Medicare program for drugs that they contend ought not to have been prescribed and would not have been if not for the fraud.  As is common, the suits are brought by private firms who also represent individual plaintiffs.

More interesting, Michaels also notes the possible tension between protective orders and the public health:

At [a 2004] meeting, we wrestled with the question of whether courts should allow information vital to protecting the public’s heath to be hidden from the public as part of a settlement. In many instances, attorneys representing both the plaintiffs and the defendants prefer to seal documents. The defendants may avoid public embarrassment and further suits; the plaintiffs (and their attorneys) get larger monetary awards by agreeing.

The drug maker Lilly has paid $1.2 billion to more than 28,000 individuals who claimed they developed diabetes or other diseases from taking the anti-psychotic drug Zyprexa. The attorneys on both sides, those representing Eli Lilly and those suing the drug manufacturer, agreed to seal the studies and other documents that supported these claims. Does the public’s right to this information trump the right of the parties to the litigation to secrecy?

He's got more, and it's well worth reading.  It's a subject I'm working on for a new article, though I'm taking off a fairly small bite, focusing on how electronic communication and anonymizing technologies change the impact of protective orders, rather than doing big picture stuff about the propriety of protective orders in the first place.

One question to which I do not know the answer: How much would registration of clinical trials and easier access to adverse event data mitigate the concerns?  Obviously that wouldn't capture everything one might want to know about off-label marketing and the like, but it seems like it should provide access to the actual data (both reliable, and in the AER context, unreliable) from which one could draw conclusions about Bad Things(tm) occurring. 

I observe that Lilly has started making available clinical trial data post-2004, and AER data is nominally public (if obscure and generally useless) too.  Seems likely to mitigate (but not, I assume, eliminate) the concerns, perhaps leaving much of what remains confidential either actual trade secrets or stupid bad documents that sound terrible but don't actually provide useful data on which conclusions should be based.

The role of plaintiffs' firms involved in individual personal injury suits also bringing the Medicare suits has some potential conflicts as well.  As Michaels points out, the plaintiffs have some incentive to keep bad documents secret if they think they can get the defendant to globally settle cases; that secrecy provides leverage.

One point of clarification on David's post: I imagine in the settlements the parties merely agreed to maintain the documents' status under the protective order issued by the judge, not to seal the documents anew.  As I've noted previously, the protective order does include a mechanism for unsealing documents that are not properly designated as confidential.  I believe an effort to do that is proceeding in the Zyprexa case.

My usual disclosure: I do a small amount of work for pharmaceutical clients in the defense of tort litigation.  Lilly is not and has never been a client of mine.

Science & Law

Apologies for the slightly below-average post counts lately -- I'm presenting at this DRI conference next week and it's taking some of my time that I might otherwise be doing this.  (Especially since I'm immediately after lunch on the second day of the conference.  I might be well-served by using actual fireworks to keep folks awake.)

Speaking of that, though, (a) if any readers will be there and want to say howdy, please do (or send me an e-mail), and (b) if any readers have good recent examples of (1) litigation-driven scholarship or (2) discovery into the peer review process, I'd love to hear about those too.  I have good ones, but it's always nice to have the most recent ones.  I'm also considering including some discussion about the expansion of the scope of what gets deemed expert testimony -- e.g., historians testifying as to a chronology of events (which sounds more like closing argument to me), so if anyone has a good recent example of that at hand, send it along.

The (Partial) Failure of Daubert

That's the conclusion David Bernstein (George Mason) in a new SSRN posting, "Expert Witnesses, Adversarial Bias, and the (Partial) Failure of the Daubert Revolution."  The abstract:

This manuscript raises two questions that have been surprisingly missing from the voluminous law review literature on expert evidence since the landmark Daubert decision. First, what is the underlying rationale for the replacement of the old qualifications-only, let-it-all standard for expert testimony with Daubert/Federal Rule of Evidence 702's requirement that all expert testimony be subject to a stringent reliability test? Second, once we have identified this rationale, has the “Daubert revolution” succeeded on its own terms?

I conclude that the implicit rationale for the reliability test is to preserve the perceived advantages of the adversarial system, while mitigating the harms to the courts' truth-seeking function by the inevitable strong biases that accompany adversarial expert testimony. These biases include the conscious biases of hired guns, the unconscious biases of other paid experts, and the selection biases that result from the fact that attorneys “shop” for their experts from a large pool of qualified individuals.

Rule 702 thus attempts to serve a worthy goal, but it far from fully succeeds in efficiently achieving this goal. First, in the context of forensic expertise in criminal cases, Rule 702 does nothing to address the huge gaps in resources between the prosecution and most defendants that severely inhibit defendants' ability to challenge unreliable prosecution expert testimony.

Second, Rule 702, applied correctly, does succeed in barring “junk science” causation evidence in toxic torts cases. However, it does so at the expense of excluding speculative evidence supporting causation, even when most experts in the field would conclude that the relevant evidence is a sufficient basis from which to find causation by a preponderance of the evidence. While Rule 702 is easily preferable to the prior overly permissive regime, it likely goes too far in insisting on a reliability test that makes the courtroom stricter about causation evidence than is the scientific community itself. The way around this problem is to amend Rule 702 to allow courts to admit educated guesses about causation, but only when nonpartisan experts, not subject to adversarial bias, are willing to make such guesses.

Finally, Rule 702 puts severe restrictions on the testimony of experience-based testimony by connoisseurs. Such experts may only testify if their field of expertise is a legitimate one, and they have proven to the court that they truly have the expertise they claim. Rule 702 also properly prevents attorneys from shopping for outlier and hired gun connoisseurs, given that there is no objective way for a jury to determine whether an experience-based expert's views are correct or representative of other experts in the field. Therefore, in the context of connoisseur testimony, courts should either replace adversarial experts with a panel of nonpartisan experts, or only allow an adversarial expert to testify if his conclusions are consistent with those of a nonpartisan advisory panel.

NYT Covers Zyprexa

And the story does a pretty good job of giving an overview, including the judge's conclusions about the paper's reporter's conduct.  The opening paragraph:

A federal district judge in Brooklyn ruled yesterday that confidential marketing materials belonging to Eli Lilly & Company about its top-selling anti-psychotic drug Zyprexa must be returned to the company by a doctor and a lawyer who, the judge said, engaged in a scheme to leak them to the news media.

The story does later note that Weinstein called Berenson's conduct "reprehensible," but I probably would have included him in the lede.

AP & Bloomberg on the Zyprexa Documents

Bloomberg has a story on Judge Weinstein's order.  The new stuff is here:

New York Times spokeswoman Diane McNulty noted that Berenson and the newspaper declined Weinstein's invitation to come to court to explain how they obtained the documents.

``Unfortunately, that resulted in an opinion which vastly overstates Alex's role in the release of the documents,'' McNulty said. ``We continue to believe that the articles we published were newsworthy and accurate and we stand by our reporting.''

Lucy Dalglish, executive director of Reporters Committee for Freedom of the Press, called the judge's order ``troubling.''

``Any time you have a federal judge finding that a reporter participated in a conspiracy, that's a frightening notion,'' she said. ``This is an area where I don't think the law is crystal clear.''

* * *

Dalglish added that, while Weinstein didn't issue any sanctions against Berenson, ``it's not often that you have a federal judge on the record finding that a reporter engaged in a conspiracy.''

The story adds that Mr. Gottstein is contemplating an appeal and that Berenson is on a leave to write a book.

Meanwhile, the AP story has the plainly inaccurate title, "Court Halts Spread of Lilly Documents," when of course the documents remain easily findable and will stay so; Judge Weinstein made no real effort to prevent their further distribution, so long as the distribution is done by someone other than those to whom they were originally leaked.  It also adds this:

Egilman's attorney, Edward Hayes, said: The judge has "told us not to do certain things, and our response is, 'We're sorry, and we'll never do it again.'"

In a statement, Gottstein insisted that his only concern was "patient safety" and that he never meant to defy the court.

"This was not a conspiracy to harm Eli Lilly," he said.

Some More on the Zyprexa Order

Some overall reactions to Judge Weinstein's order (linked to below):

The basic takeaway is that Judge Weinstein is completely convinced that Dr. Egilman, James Gottstein, and Alex Berenson conspired (a term he uses, along with "conspiracy," thirty-eight times in the order) to avoid the protective order, and he wants to do what is practical to mitigate the effects of that conspiracy.  But he recognizes the futility of really preventing the documents' distribution (something I've noted before too).  The bottom line result -- enjoining the people who received the documents from Gottstein and have not returned them, refusing to enjoin websites, and presumably scaring the hell out of the "conspiracy" trio -- tracks those conclusions precisely.  The actual impact on the availability of the documents will be approximately zero.

I'm a little skeptical of the Court's First Amendment conclusions, but I'm not a con law guy either, so my view is relatively uneducated.  And the breadth with which he sees his powers to enjoin seems perhaps enthusiastic, but it's not something I've looked at carefully.

The order points up what is a real problem (one I'm writing about in long form, hopefully to get submitted this spring) -- that past treatment of leaking documents in disregard of protective orders -- hasn't put in place the right kind of incentives to ensure that orders are enforced.  When litigants and courts perhaps once could hope to unring the bell, today it's impossible with internet distribution.  Judge Weinstein certainly hints in this order that he's going to make at least two of the three involved very uncomfortable, but to my knowledge courts have been if not blase, not particularly enthusiastic about tracking down or punishing those who violate their orders.  He expressly acknowledges the need to set up proper incentives:

Conspirators in the instant case who deliberately thwarted a federal court’s power to effectively conduct civil litigation under the rule of law, as well as those in concert with them, should be enjoined to deter further violations of this and other courts’ orders.

* * *

It is not necessary now to decide whether in the long run the public was better served by this conspiracy to flout CMO-3 than by seeking direct and open revelation through amendment of the court’s protective order.  Even if one believes, as apparently did the conspirators, that their ends justified their means, courts may not ignore such illegal conduct without dangerously attenuating their power to conduct necessary litigation effectively on behalf of all the people.  Such unprincipled revelation of sealed documents seriously compromises the ability of litigants  to speak and reveal information candidly to each other; these illegalities impede private and peaceful resolution of disputes.

There's another effect of electronic communication that I don't think I've mentioned before (and that I'll also address in the article), and that's the exponential growth of the number of pages in play.  I don't know how many pages have been produced by Lilly; the Order references "millions" of documents.  One case I was involved in had, if memory serves, something approaching tens of millions of pages produced, with individual witnesses sometimes having hundreds of thousands of pages of documents on a server.  Colleagues who had been involved in pre-e-mail litigation suggested that it would have been uncommon to see even a million pages in one case; perhaps someone else can confirm. 

It boggles the imagination to think that a litigant can do a particularly good job of designating documents accurately as to confidentiality, and no doubt it frustrates people like Dr. Egilman to see documents he believes are inaccurately designated as confidential (especially since he is, I think, unlikely to conclude that Lilly's commercial concerns are a reasonable basis for keeping many thinigs confidential).  And that frustration -- that view that there is massive overdesignation -- may well make experts, attorneys, litigants, and others more prone to want to disregard protective orders.  (It's worth observing that Judge Weinstein concludes that in fact the bulk of the documents were appropriately designated as confidential.)

Of course, neither Gottstein, Egilman, Berenson, nor indeed anyone else (besides apparently some third-party payors) made any effort to follow the mechanism set forth in the protective order to de-designate the documents.  As I've mentioned before, if you're looking for a judge who is likely to be friendly to such an effort, Judge Weinstein is a good one.  But there was no effort at all.

And of course, the plaintiffs' signing on to keeping the documents confidential may reflect a recognition that keeping the documents secret gives the plaintiffs greater leverage in further settlement discussions (recall that tens of thousands of cases have already settled).

In any event, some money quotes:

A New York Times reporter, Alex Berenson, was aware of the protective order.  He discussed with a plaintiffs’ expert, Dr. David Egilman, means of escaping the order’s restrictions and obtaining protected documents in the expert’s possession . . . even though Egilman had agreed in writing to be bound by the order. . . .

Both Berenson and Egilman were cognizant of the fact that paragraph 14 of CMO-3 took account of the possibility that the protected documents could be subpoenaed by courts or executive agencies.  So Berenson provided Egilman with the name of an Alaska attorney, James Gottstein, unconnected to the instant litigation, who might be willing to employ a pretense to subpoena the documents and help disseminate them in violation of the protective order. . . .

To carry out the scheme for obtaining and disseminating the protected documents, Gottstein intervened in a state case in Alaska wholly unrelated to Zyprexa.  In that case, he then subpoenaed from Egilman confidential documents he knew to be under the protective order which bore no relevance to the Alaska litigation.  The subpoenaed documents were sent by Egilman to Gottstein pursuant to an expedited amended subpoena about which Lilly was deliberately kept in the dark so that it would be unable to make a timely objection. . . . Gottstein immediately sent the confidential documents on to Berenson and others. . . . .

None of the three conspirators, Berenson, Egilman, and Gottstein, sought a lifting or modification of the protective order, despite the declassification procedures provided for in paragraph 9 of CMO-3.  See In re Zyprexa, No. 04-MD-1596, 2004 WL at *5.

While the order ends up rejecting some of the arguments (presented by the EFF and others) that the breadth of the injunction sought by Lilly would run into constitutional problems, Judge Weinstein does explicitly recognize the First Amendment relevancy:

A perplexing issue is presented by Lilly’s request for an injunction against websites to which the conspirators sent the documents or which might have been used for further dissemination by those to whom the documents were originally sent. . . .  The internet, with its almost infinitely complex worldwide web of strands and nodes, is a major modern tool of free speech and freedom both here and abroad.  Its reach extends as far as, and perhaps exceeds, that of newspapers and other traditional media.  The law is rightly hesitant about allowing government –– including the courts ––  to inhibit and restrict the use of such modern instruments of communication.  See U.S. Const. amend. I.

I think it was perhaps more significant than was made explicit here that the PSC was on board:

Irresponsible people may exercise their own right and opportunity to speak in a manner abusive and constrictive of the rights of others on the internet, in the press, and in other fora.  Those whose rights have been abused by the conspirators in violation of the court’s protective order include Lilly and tens of thousands of plaintiffs and their attorneys who depended upon CMO-3 and sealing orders of the court to effectively prosecute this important litigation without unnecessary breach of the parties’ privacy.  It is significant that both the PSC and Lilly support the issuance of the injunction now being issued.

On the notion that the Times's situation is analogous to the Pentagon Papers:

Nor is this a case of a newspaper obtaining, with clean hands, documents provided to it by government employees, whistleblowers, or protestors.  See Smith v. Daily Mail Publ’g Co., 443 U.S. 97, 103 (1979) (“[I]f a newspaper lawfully obtains truthful information about a matter of public significance then state officials may not constitutionally punish publication of the information, absent a need . . . of the highest order.”) (emphasis supplied).  It is unlike New York Times Co. v. United States, 403 U.S. 713 (1971) (hereinafter “Pentagon Papers”).  In the Pentagon Papers case, there was no suggestion that the documents were purloined at the New York Times’ or Washington Post’s instigation.  Here, a reporter was deeply involved in the effort to illegally obtain the documents. . . .  Affirmatively inducing the stealing of documents is treated differently from passively accepting stolen documents of public importance for dissemination. . . .  But see Bartnicki v. Vopper, 532 U.S. 514, 528-29 (2001) (noting that the issue has been left open).  The New York Times itself appears to recognize the distinction.  See The New York Times, Ethical Journalism: A Handbook of Values and Practices for the News and Editorial Departments, 9 (Sept. 2004) (“Staff members must obey the law in pursuit of news.  They may not break into buildings, homes, apartments, or offices.  They may not purloin data, documents or other property, including such electronic property as databases and e-mail or voice mail messages.  They may not tap telephones, invade computer files or otherwise eavesdrop electronically on news sources.  In short, they may not commit illegal acts of any sort.”).

On what happened after Gottstein started to distribute the documents:

Individuals to whom Gottstein sent the documents began devising schemes to evade court orders to return the documents even before any such orders had been issued.  In an email dated December 16, 2006, Robert Whitaker wrote to Gottstein: “I would consider building a website that would, ahem, make all the documents available.  What could they do to me?  And how could they know how the documents got to me?  There are several channels apparently that could be the source.  You should proceed now in whatever way makes it easiest for you, and let others worry about getting this information out or making it public.”  Pet’r Findings of Fact, supporting ex. 30.

[Time to make dinner for the kids.  More later.]

 

Zyprexa Order Issued!

Good heavens, that was fast.  Briefing finished yesterday, and here's the order: Download memorandum_final_judgment_order_injunction_07504.pdf

I haven't read it yet, but it appears to conclude that the immediate recipients are still within an injunction, but that secondary (and those further out) are not.  A very quick glance suggests that this paragraph is a reasonable summary of what Judge Weinstein thinks about Egilman, Gottstein, and Berenson:

Berenson’s, Egilman’s, and Gottstein’s brazen flouting of this court’s protective order raises serious questions about their responsibility.  The court, based on the evidence before it, is not satisfied that they can be counted on to return all copies of the documents they may have in their possession or control.  Egilman and Gottstein are therefore being permanently enjoined as noted in Part IV.H.5, supra.  Berenson is not being enjoined since no injunction against him has been sought by Lilly.  See Part IV.H.4, supra.

More -- much more -- to come, probably this afternoon.