The Story of CPRIT, Part 2: A Problematic Grant

The grant that upset Dr. Gilman so much that he chose to resign was an award of $22 million dollars for one year.

The award had been presented to the Oversight Committeee and approved without going through any scientific review. It was a combination award to Rice and to an organization, IACS (Institute for Applied Cancer Science), associated with Lynda Chin, a scientist and wife of the president of M.D. Anderson, Ronald DePinho. Remarkably, the IACS portion of the award had not been reviewed by the provost of either Rice or M.D. Anderson, and after reaching CPRIT, it was rushed through the CPRIT approval process in a very short timeframe in March 2012, and not at all in the regular way of electronic submission and a review process mentioned in yesterday’s post.

Apparently, this had been in the works for some time. CPRIT memos show discussion of this between Jerry Cobbs, the Chief Commercialization Officer, and the IACS people as early as January. And Charles Sherr, a member of the Scientific Review Council, recounted in a May email that he had run into DePinho in October at the annual meeting of the American Academy of Arts & Sciences.

Over cocktails, I ran into Ron who immediately told me that he was in direct touch with ‘the higher-ups’ who run CPRIT and that the program and Al would soon be under pressure to change the current approach. . . . [I suggested] he might speak directly to Al. Well appreciating Ron’s malignant ambition . . . , I was not blind-sided later by the proposal to mount ‘a Lynda Chin Institute’ under the auspices of Ron and MDACC. It is  my firm belief that Ron has played a direct and important role in helping to orchestrate what is, in effect, a coup d’etat.

Dr. Gilman, on the other hand, was very much blindsided.

A week before the Oversight Committee meeting, I learned essentially by accident that CPRIT was to make an $18M aware to Lynda Chin to fund the Institute for Applied Cancer Science. The proposal on which this was based was less than 7 pages, was submitted via the back door on March 11, and was presented to the Oversight Committee for funding less than two weeks later.

When he discovered it, he was extremely angry.  Bill Gimson, the executive director of CPRIT, wrote to a member of the Oversight Committee:

Al is very, very upset that the Lynda Chin operation at MD Anderson is coming in as an incubator – he feels that she did that to avoid the research peer review and that it is not an incubator because it is research.

Earlier, Dr. Gilman had bought off on approving a $4 million grant for an incubator sponsored by Rice University, one pushed heavily by Charles Tate, a venture capitalist and commercialization advocate appointed to CPRIT’s Oversight Committee by Dewhurst (Tate had made campaign contributions amounting to hundreds of thousands of dollars to Dewhurst). The incubator was to be allowed to chose promising projects without the usual scientific oversight. (My personal thought is that this was possibly a tactical error on Gilman's part that he agreed to it, as this project was designed to be the "foot in the door" for enabling many future projects to evade the regular process of scientific review, judging by the fact that it was later described by a proponent as a commitment "to run a separate line aimed at commercialization that did not rest on scientific review.") Now, the IACS’s short proposal was joined with the Rice incubator project and the grant amount vastly increased under the rubric of describing the whole thing as appropriate for an “incubator.” As Gilman angrily wrote:

An award of $18 million for a research proposal without a research review – based on the administrative act of bolting it to an incubator proposal and the claim that this is an appropriate award for an incubator – is amazingly transparent. Deny it all you want, everyone who has looked at the proposal realizes that it is a joke. Everyone will also wonder why they cannot submit a seven page general description of a modus operandi, free of detail, and receive a multi-million dollar award if they simply say, ‘I hope to commercialize something, sometime.’

In addition, plans going forward by those who wanted to remold CPRIT were for commercialization projects to take around half of remaining monies after administration costs and a statutorily-designated 10% for cancer prevention research and activities. This was very different from what had occurred up to that point. The bulk of over the $700 million already awarded had gone to research. Matt Winkler, a member of CPRIT’s Scientific and Prevention Advisory Council, stated blandly:

We should really get out of the business of copying what the NIH does.

Joined with the idea that many “translational” projects should NOT be subject to scientific review, this was too much for Dr. Gilman – and ultimately for many others – to swallow.

Not science but business was the new order of the day at CPRIT, as its leaders made clear when the news of Dr. Gilman’s resignation was leaked to the press. Bill Gimson, the CPRIT Executive Director, defended CPRIT's increased emphasis on commercialization, stating in June:

We're going to reinvent ourselves on a regular basis.

As to the celerity with which the grant was approved, he said:

We did indeed move quickly with the review of the collaboration between Rice and MD Anderson, just as we have fast tracked other very exciting and potentially lifesaving commercial ventures and research recruitment awards – which can be approved in as little as a couple of weeks.

 Dr. DePinho wrote the Houston Chronicle to contend that: 

ACS is a game-changer - not a traditional research undertaking - that provides a robust pipeline for successful drug development. ... Because it is not a research project, no in-depth science was included. ... With its industry-seasoned professional staff numbering 56, the IACS conducts rigorous, goal-oriented, milestone-driven activities …Some may choose to call our proposal ‘research.’ We call it business, and we are confident Texans will be the beneficiaries. ... The current output of the IACS pipeline will prove its commercial impact in the near future.

Why Do We Eat? A Neurobiological Perspective. Part V

In previous posts, I explained that food intake is determined by a variety of factors that are detected by the brain, and integrated by circuits in the mesolimbic system to determine the overall motivation to eat.  These factors include 'homeostatic factors' that reflect a true energy need by the body, and 'non-homeostatic factors' that are independent of the body's energy needs (e.g. palatability, habit, and the social environment).

In this post, we'll explore the hedonic system, which governs pleasure.  This includes the pleasure associated with food, called palatability.  The palatability of food is one of the factors that determines food intake.

The Hedonic System

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The Story of CPRIT, Part 1: A Promising Start

HC Renewal readers who don’t live in Texas may not have followed the saga of the Cancer Prevention & Research Institute of Texas (CPRIT). It’s a fascinating story which will take me more than one post to tell even a partial version of, especially since a wealth of information is available because of FOIA requests and the superb reporting of the Houston Chronicle and The Cancer Letter.

A constitutional amendment authorizing CPRIT was proposed to the voters in November 2007. (In Texas, lots of things that could be passed legislatively elsewhere require amending the constitution, so that it’s now a very long document indeed.) With a pot of money second only to the NIH’s (up to $300 million in bonds per year was authorized for 10 years for a total of $3 billion), its ambitious goal was to make progress against cancer while making Texas a real leader in cancer research. Enabling legislation was passed and the institute got off to a good start in 2009 by putting together a leadership team that included Nobel prize winner Alfred Gilman as Chief Scientific Officer and Phillip Sharp (another Nobel prize winner) as head of its Scientific Review Council. The press release announcing Sharp’s appointment stated:

Research and prevention grant applications will be assessed using an external- to-Texas peer review process. . . . [P]olicies and processes [are being formalized] that will ensure CPRIT funds only the best scientific research and prevention projects, measures its success and shares results on progress so that Texas will lead the nation as a model for cancer research and prevention programs.

The process was formalized; and the 2009 Policies and Procedures Guide has a diagram showing that grants were supposed to be submitted electronically, be triaged for merit, and (if they survived initial triage) first go through scientific peer review, then go through commercialization review for business worthiness (only if they were translational projects), be recommended for funding, and then be submitted for review and final funding approval by the CPRIT Oversight Committee (cf. State Audit report, Appendix 5).

Peer review teams of eminent out-of-state scientists were put together, the process got going, and projects deemed worthy by the Scientific Review Council were routinely approved by CPRIT’s Oversight Committee, a group of political appointees plus the Attorney General and the State Comptroller. CPRIT money helped attract some eminent researchers to the state. 

But then, it all fell apart.

Dr. Gilman, the Nobel laureate who had set up the scientific review process, submitted a letter of resignation in May 2012, effective the following October. In his resignation letter, he stated that he would like “to prevent further award of vast funds for research programs ostensibly within incubators that were not described and therefore could not have been reviewed.”

The grant that he refers to and that had upset him so mightily was a large one-year combined award approved in March for an incubator at Rice University and for MD Anderson’s Institute for Applied Cancer Science.  

Why was he so upset about this particular award? More on that in the next installment.

A Condemnation of Suppression of Medical Research... by Ben Goldacre in the New York Times

Amazingly, this topic now seems to be in the mainstream.

The Goldacre Version in the New York Times in 2013

In his op-ed, Ben Goldacre introduced it thus:

the entire evidence base for medicine has been undermined by a casual lack of transparency. Sometimes this is through a failure to report concerns raised by doctors and internal analyses, as was the case with Johnson & Johnson. More commonly, it involves the suppression of clinical trial results, especially when they show a drug is no good.

He noted that this problems was supposed to be fixed by the registration of clinical trials, and by changes in editorial policies at medical journals:

many in the industry now claim it has been fixed. But every intervention has been full of loopholes, none has been competently implemented and, lastly, with no routine public audit, flaws have taken years to emerge.

 The Food and Drug Administration Amendments Act of 2007 is the most widely cited fix. It required that new clinical trials conducted in the United States post summaries of their results at clinicaltrials.gov within a year of completion, or face a fine of $10,000 a day.  But in 2012, the British Medical Journal published the first open audit of the process, which found that four out of five trials covered by the legislation had ignored the reporting requirements. Amazingly, no fine has yet been levied. 

An earlier fake fix dates from 2005, when the International Committee of Medical Journal Editors made an announcement: their members would never again publish any clinical trial unless its existence had been declared on a publicly accessible registry before the trial began. The reasoning was simple: if everyone registered their trials at the beginning, we could easily spot which results were withheld; and since everyone wants to publish in prominent academic journals, these editors had the perfect carrot. Once again, everyone assumed the problem had been fixed. 

But four years later we discovered, in a paper from The Journal of the American Medical Association, that the editors had broken their promise: more than half of all trials published in leading journals still weren’t properly registered, and a quarter weren’t registered at all. 

Goldacre's conclusions were:

Withholding data not only misleads doctors and patients; it’s an insult to the patients who have participated in clinical trials, believing that they were helping to improve medical knowledge. 

Medicine routinely overcomes enormous technical challenges, and there is nothing complicated about the changes needed to prevent Johnson & Johnson, or Roche — or anybody — from withholding information.

Hear, hear!

Our Version, Starting in 2003

Note that 10 years ago, in 2003, in my article on American health care dysfunction that could have been only published in Europe, (Poses RM. A cautionary tale: the dysfunction of American health care. Eur J Intern Med 2003 Mar;14(2):123-130.  Link here)  I noted that an important cause of this dysfunction is that:

the scientific basis of medicine is increasingly under attack.

The integrity of medical research has been violated by the deliberate suppression of its results.

At that time, I suggested one solution would be:

Medical schools and universities must re-affirm their support of scholarly work in the spirit of free enquiry,...

Furthermore, in one of our first posts on Health Care Renewal in December, 2004, in the context of the discovery of internal company documents (in this case, from Eli Lilly) that showed that information about the adverse effects of a drug (in this case, increased aggression associated with fluoxetine, that is, Prozac), we wrote,

The increasingly complex story of suppression of SSRI research seems to be part of a growing epidemic of suppression of medical research.

Let's say it again. Withholding data from clinical research is unethical because:
1. it breaks the promise to research subjects that their voluntary participation has scientific or social value, but undisseminated research has no value; (See Emanuel EJ et al. What makes clinical research ethical? JAMA 2000; 283: 2701-2711.)
2. it impedes scientific progress;
3. it prevents patients from receiving the best possible medical care.

But until this unethical behavior starts having negative consequences for its perpetrators, the epidemic of research suppression is likely to continue. 

Note the similarity to what Goldacre published in the Times yesterday.  You heard it here first.

Summary

To date we have published 102 posts with the label "suppression of medical research."  Obviously, Ben Goldacre's NY Times op-ed shows that suppression of research still rarely leads to negative consequences for its perpetrators.  Obviously, by making drugs, devices, and other health care interventions appear safer and more effective than they really are, suppression of medical research has lead to huge revenues for health care corporations, and has made many health care executives exceedingly rich, and many of the health care professionals and academic leaders who have enabled or implemented research suppression somewhat rich.  In the face of such perverse incentives, until we end the impunity of those who suppress medical research (and by the way, those who authorize, direct, or implement all sorts of other unethical, criminal and corrupt behavior we discuss on Health Care Renewal) things will not get better.  I can only hope that having this subject appear in a New York Times op-ed may lead to some real progress.

ADDENDUM (2 February, 2013) - see also comments on 1BoringOldMan blog. 

Modern Healthcare: "Health IT Iconoclasts"

The healthcare executive-targeted journal "Modern Healthcare" has named Dr. Ross Koppel, Dr. Deborah Peel, Dr. Larry Weed, and yours truly as "healthcare IT iconoclasts."  Dr. William Bria corroborated the importance of iconoclasty in this domain.

(I would rather see the term "defender of patient's rights" rather then "iconoclast", but I'll settle for the latter if it gets the message out.)

Author Joe Conn writes:

... health IT has long had its critics, even among its pioneers and proponents, as these four prominent health IT iconoclasts will attest. All four consider themselves to be proponents of health IT, but they rail against a tide of health IT boosterism. Their targets: misplaced priorities, failing to promote EHR usability and interoperability, inadequate concern for patient safety and privacy, overemphasizing EHR adoption, understating IT costs and overestimating the return on public IT investments.

He then profiles the four.

On Univ. of Pennsylvania professor and industry punching-bag Dr. Ross Koppel:

Researcher Ross Koppel started an uproar in 2005 when he and a colleague coauthored an article in the Journal of the American Medical Association that found a first-generation computerized physician order entry system (CPOE) at the Hospital of the University of Pennsylvania was simultaneously creating new errors even as it reduced others.

Koppel’s bombshell—he’s now an adjunct professor of sociology at the University of Pennsylvania— brought down the wrath of information technology boosters. The Healthcare Information and Management Systems Society, a health IT trade group, challenged the study’s “methodology and its subsequent outcomes,” and criticized its authors for their “limited view” and not “looking at the big picture.”

... In 2009, he revealed in another JAMA article that health IT vendors’ contracts included “hold harmless” clauses that shielded software developers from legal liability for medical errors their systems caused, even if the developers had been warned about the defects. “That got me major upheaval,” the worst of his career, Koppel recalls.

On privacy advocate, psychiatrist Dr. Deborah Peel (no relation to Emma Peel, although there are similarities in the "has guts" department):

“Let’s face it,” Peel says, “HHS is the agency that eliminated patient control over electronic medical records and has remained hostile to patients’ rights ever since.”

Days before the 2002 revision [HHS redraft of the privacy rule of the HIPAA Health Insurance Portability and Accountability Act] went into effect, a group of patients calling themselves Citizens for Health, and more than dozen other plaintiffs, including Peel, sued HHS Secretary Tommy Thompson in federal court, alleging the revisions violated patients’ constitutional rights to privacy. They lost at both the trial and appeals-court levels and were denied a hearing on appeal to the U.S. Supreme Court in 2006.

Peel launched the not-for-profit Patient Privacy Rights Foundation in 2003.

... “Where I’m coming from is, I’ve spent all this time in a profession with people being hurt,” Peel says. “Starting in the 1970s, when I first let out my shingle, people came to me and said, if I paid you in cash, would you keep my records private. Now, we’ve got a situation where you don’t even know where all your records are. We don’t have a chain of custody for our data, or have a data map” to track its location.

 On SOAP-note and Medical Informatics pioneer Dr. Larry Weed:

It’s a rotten system,” declares Dr. Lawrence Weed, who at age 89 is the dean of healthcare information technology iconoclasts.

Weed isn’t disparaging any particular brand of electronic health record system. A dismissive “they’re inadequate” would fairly well cover a Weed-guided tour of today’s EHR systems.

“People don’t get the general picture,” he says. “It’s broken. It’s basically an unsound system.” By that he means the entire healthcare system, but not because its providers are using faulty information technology, but because they’re using IT the wrong way, at least in part.

... In 1984, to help physicians cope [with the knowledge explosion], Weed developed a computer-based, diagnostic support system he called the problem-knowledge coupler. The software company he founded, but is no longer with, PKC, now part of Sharecare, still sells the system. Weed still proselytizes with fervor, calling for the use of computers to store, retrieve and apply medical knowledge.

On me:

The title of Dr. Scot Silverstein’s teaching website at Drexel University, “Contemporary Issues in Medical Informatics: Good Health IT, Bad Health IT, and Common Examples of Healthcare IT Difficulties,” [link] summarizes the veteran physician informaticist’s general outlook on the current state of affairs in health information technology.

It tells you nothing, however, of the passion with which Silverstein speaks or writes about the subject. Also a frequent contributor to the popular reformist “Healthcare Renewal” blog, Silverstein writes with the fire you might expect coming from a self-described computer geek who says he has witnessed a faulty electronic health-record system mysteriously drop a single medication from a patient’s medication list. That missing drug led to a medical error that resulted in a year of suffering and, eventually, that patient’s death, he says.

Silverstein’s passion is even more understandable when he tells you that patient was the doctor’s own mother.

... The health IT world, Silverstein says, parts neatly between “good IT” and “bad IT.” There are those who push hard for the good and complain about the bad, physicians and other clinicians he calls “pragmatic,” and for whom he has sympathy and respect. And then there are those who stay silent, ignoring or acquiescing to the bad, the “hyper-enthusiasts” for whom he holds only unmitigated scorn. “The doctors who don’t speak up about health IT, who work around it, which can cause its own bad results, those are traitors to the oath they took to first do no harm,” he says.

“Physicians are still being accused of being Luddites for not adopting this stuff,” Silverstein says. “Physicians are not Luddites. When it’s good IT, it’s used. I see the tension now between hyper-enthusiasts, who turn a blind eye to the negatives, and pragmatic physicians and nurses who have work to do.”

Finally, Dr. William Bria, longtime president of the Association of Medical Directors of Information Systems (AMDIS) sums up the article this way:

... When it comes to the criticism, “the one thing we can’t do with this information is to ignore it."

“Many, many technologies have come and gone in the history of medicine over the centuries, and it often has been a maverick physician that has called a timeout on ineffective medications or treatments.

“There is little question that, going forward, medicine will be using information tools,” Bria says. “However, I believe it’s becoming also very apparent that we need a modulation and a proper regulation of information technologies used in day-to-day care.”

Amen to that.

The article is available here.

-- SS

The lengths a hospital will go to in order to protect their EHR - Motion for Reconsideration of Denial of Motion for Reconsideration of Denial of Objections

My mother was injured and then died as a result of an EHR foul-up.  She sued the hospital where the mid-2010 accident occurred while she was still lucid, and I am now substitute plaintiff.  Yet the case has been held up through the defense (mis)using court process to stall.

It seems the lengths a hospital will go to in order to protect their EHRs (i.e., from Discovery by an expert such as myself, which could show many problems) are amazing.

To wit, their latest filing, in an attempt to throw a monkey wrench into the gears of the legal discovery process:

2/1/2013

Motion

BY [redacted] HOSPITAL MOTION FOR RECONSIDERATION OF JANUARY 17, 2013 ORDER DENYING MOTION FOR RECONSIDERATION OF COURT ORDER DATED JUNE 22, 2012 WITH MEMORANDUM OF LAW WITH SERVICE ON 02/01/2012

They've filed a motion asking the Court to reconsider its decision that denied their mid-2012 motion asking the Court to reconsider its denial of their objections to the legal paperwork.

Yes, that probably needs to be read several times in order to be understood; I cannot simplify it any further ...

The new motion is a mere 521 pages in length (the original Motion for Reconsideration was a slim 485; of course they charge the hospital by the hour for document preparation and electronic filing with the Court).

The major objection about the paperwork is, in essence, that a "Certificate of Merit" (a certification of case merit by a qualified medical professional) needed to be filed not just for Defendant (the hospital) but for each and every employee/agent for whom the Defendant is vicariously liable under the doctrine of Respondeat Superior:

Respondeat superior (Latin: "let the master answer"; plural: respondeant superiores) is a legal doctrine which states that, in many circumstances, an employer is responsible for the actions of employees performed within the course of their employment. This rule is also called the "Master-Servant Rule", recognized in both common law and civil law jurisdictions.

A major problem with this claim is that the law simply says otherwise.  Also, Certificates of Merit have, under the identification field where the sued party's name is penned in, the label "defendant" ... not "defendant, employees, agents, their uncles and aunts, and their little dogs too for whom defendant is vicariously liable."  Not to mention, among other issues, that such misconceptions are specifically put to rest by the actual Civil Procedural Rules Committee rules as published by the state's court administrative body:

"The [certificate of merit] rule requires the filing of only a single certificate of merit as to a claim against a defendant that is based on the activities of licensed professionals who are not named in the action."

Such a certificate was timely filed.  In fact, one Certificate was timely filed against the defendant hospital for corporate negligence, and another timely Certificate was filed for defendant's vicarious liability.

That's why the court threw out the objections, and the Motion for Reconsideration of its denial of the objections..

In defense of their position that Certificates for each person for whom the defendant is vicariously liable should have been filed (which is an especially frivolous argument since there is a statement in the law that they do not need to be named), the hospital defense ignored all plaintiff's arguments regarding the filing of the Certificates of Merit such as above.  It then cites two cases where the Certificates of Merit were filed over a year late (there is a 60 day limit) or not filed at all.  

But they didn't stop there.  The defendants also wanted the (local) court to 'certify' (give permission for) them to appeal the denial of their objections to Superior Court (the certification may be done if the issues at law are felt possibly controversial).  The local court threw that request out, too.

The defense appealed to Superior Court anyway, apparently claiming manifest injustice was done by the local court.  Several hundred more pages, more fees.  The Superior Court dismissed the appeal - or, perhaps stated more accurately, refused to even consider it.

All this eats up time.

Now, I'm not an attorney, nor do I have access to the major legal databases.  However, Google is getting to be very good at pulling up legal cases due to its indexing of many other resources, such as legal books and publications and public case docket repositories.

When I Google "Motion for Reconsideration of Denial of Motion for Reconsideration" or "Motion for Reconsideration of Motion for Reconsideration", very little comes up.  One case is from the early 1990's in the High Court of American Samoa. (If you know where that is without looking it up, you're more geographically literate than I.)

When all else fails ... throw a monkeywrench into the Wheels of Justice  ... and be paid handsomely for it!

The Defense stalling maneuvers have served to help me advise other Plaintiff's attorneys in EHR-related medical malpractice and evidence spoliation matters (the motion above will be presented at my upcoming talk at the American Association for Justice Winter Conference in Florida as an example of how far a hospital will go to protect their EHR).  

The stalling has also been serving as a useful learning experience for me regarding the working of the Court system, enhancing my abilities to assist the Plaintiff's side.  Perhaps I should be paying tuition to the Defense in my mother's case ...

(The Plaintiff's Bar - and injured patients - need help.  I have, for instance, learned in sworn testimony of hospital IT experts that some major commercial EHR's permit a clinician to alter their notes prior to their final "signoff" and resultant "record lock" -- which can be days later -- without leaving an electronic trail or any evidence whatsoever of the changes.  I have learned that some EHR's permit late-entered notes to appear in apparent chronological sequence in an EHR printout with whatever apparent time is desired.  I have learned that the audit trails and other metadata themselves of major commercial EHRs can be altered by someone with sufficient database privileges with no trace, save for perhaps database engine transaction logs on backup tapes, highly difficult to retrieve.)

In effect, one motive for hospitals to acquire EHR's might be the EHR's abilities to facilitate "retroactive risk management" through, in essence, alteration of history.

Finally, I hope I won't have to see a "Motion for Reconsideration of Denial of Motion for Reconsideration of Denial of Motion for Reconsideration of Denial of objections to the paperwork."

-- SS

Why Do We Eat? A Neurobiological Perspective. Part IV

In this post, I'll follow up on the last post with a discussion two more important factors that can affect energy homeostasis and therefore our food intake and propensity to gain fat: age and menopause.

Age

Although it often isn't the case in non-industrial cultures, in affluent nations most people gain fat with age.  This fat gain continues until old age, when many people once again lose fat.  This is probably related to a number of factors, three of which I'll discuss.  The first is that we tend to become less physically active with age.  The second, related factor is that we lose lean mass with age, and so energy expenditure declines.

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