Monday, February 11, 2013

No Improper Influence: CIRM Defends 'No Actual Conflicts' Claim

Earlier this month the California Stem Cell Report  published an item that said:
“In the wake of recent considerable criticism concerning conflicts of interest at the $3 billion California stem cell agency, its leaders have taken to saying 'no actual conflicts' have been found at the agency.
“That assertion is simply not true.”
We asked the stem cell agency if it would like to respond and said that its response would be carried verbatim. The agency's comments are below. Our take on the response follows the CIRM comments, which were authored by Kevin McCormack, the agency's senior director for public communications and patient advocate outreach.

In David Jensen’s recent blog about the stem cell agency he claims to “debunk” claims that there have been no actual conflicts in CIRM’s funding decisions saying “the agency has a long history of problems involving conflicts of interest, 'actual' and otherwise.” In fact, in the cases cited by Mr. Jensen, show 'otherwise' is the appropriate word here because as we’ll show CIRM’s conflict procedures worked and the funding decisions were not affected by any improper influence.
Let’s take it case by case, looking at each instance of a “conflict” cited by Mr. Jensen.
John Reed
In 2007, John Reed, a member of the stem cell agency’s Governing Board, contacted staff in his capacity as the president of the Burnham Institute after the Board approved a SEED grant award to a Burnham investigator. Dr. Reed did not participate in the Board’s decision to approve the award and played no role in that decision. All he did was send a letter to CIRM staff after the Board meeting to provide factual information in response to technical questions raised by CIRM staff concerning the investigator’s eligibility for an award. Those questions ultimately led staff to reject the grant. Because the Board had already made the decision to award the grant, it did not occur to Dr. Reed that the conflict rules would prevent him from contacting staff to provide relevant information. And why would it? The decision was made so there was nothing to influence. After CIRM staff received Dr. Reed’s letter, they informed Dr. Reed that he must refrain from participating in any way in CIRM's consideration of the Burnham grant. In addition, CIRM staff did not consider the letter in conducting their administrative review of the Burnham grant and their determination that the investigator was not eligible did not change. The FPPC determined that, although Dr. Reed’s conduct raised ethical concerns, he had not violated conflict of interest laws because he attempted to influence a decision that had already been made. Furthermore, Dr. Reed’s conduct did not affect a CIRM funding decision because the grant was rejected by CIRM staff.
New Faculty Awards
When a candidate applies for a CIRM New Faculty Award it is standard practice for them to include a letter of support from the institution where they hope to be working. In December 2007, during a review of applications for New Faculty Awards, CIRM staff discovered that ten applications were accompanied by letters of institutional support signed by members of the Board. This was due to a miscommunication by staff, a poorly drafted memo to Board members leading them to think it was OK to sign the letters of institutional support. The error was discovered before the Board considered any of the applications. CIRM staff determined that the letters could be perceived to create a conflict of interest and so, to avoid even the appearance of a conflict, CIRM staff disqualified the ten applications. As a result, the applications were not presented to the Board for its consideration, thereby avoiding any potential for a conflict of interest in a funding decision.
John Sladek
In 2011, while preparing the public summary for Basic Biology III applications, CIRM staff discovered that Dr. John Sladek was one of several co-authors on scientific publications with a researcher who was listed as a consultant on a CIRM grant application. This is a technical violation of the Grants Working Group (“GWG”) conflict policy, which prohibits a member of the GWG from participating in the review of an application if the member has co-authored papers with a salaried investigator listed on a CIRM application within a three year window. It should be noted, however, that Dr. Sladek’s participation in the review of the application would not have constituted a conflict of interest under state conflict of interest laws because Dr. Sladek did not have a financial interest in the application. In addition, the amount of funding involved – approximately $3,000 of salary per year for three years, less than one percent of the total award – was not material, and Dr. Sladek did not stand to receive any financial benefit from the application. Finally, Dr. Sladek’s participation in the review did not affect the outcome because the application was not recommended, or approved, for funding.
The three instances cited by Mr. Jensen share two common features. First, CIRM staff identified the potential for a conflict before any funding decision was made. Second, CIRM’s funding decisions were not affected by any improper influence.
Ted Love
Mr. Jensen also cites the service of Dr. Ted Love, a member of the Board who volunteered his time to assist CIRM in offering his scientific and medical expertise, as evidence of a conflict of interest. Although Mr. Jensen insinuates that Dr. Love’s service constituted a conflict of interest, he does not cite any facts, except Dr. Love’s “deep connections to the biomedical industry.” But the fact that Dr. Love has experience in the biotech industry does not constitute a conflict of interest, and as a member of the Board and as a volunteer to CIRM, Dr. Love abided by CIRM’s conflict of interest policies.
In the past Mr. Jensen has criticized the stem cell agency for its lack of connections and engagement with industry. In this case he criticizes us precisely because of our connection and engagement with someone who has industry experience.
Venture Capital Firm
Mr. Jensen also suggests that a conflict of interest arose from the fact that “iPierian,Inc., whose major investors [a venture capital firm] contributed nearly $6 million to the ballot measure that created the stem cell agency, has received $7.1 million in awards from the agency.” While it is true that Proposition 71 involved a multi-million dollar campaign, the funding for the campaign came primarily from individuals who had a family member who suffered from a chronic disease or injury, including individuals associated with a venture capital firm. The firm itself did not contribute to the campaign, nor did the campaign accept contributions from biotechnology or pharmaceutical companies. Furthermore, the venture capital firm did not invest in a CIRM grantee; rather, it invested in a different company which subsequently merged with yet another company to form an entity that later applied for, and was awarded a CIRM grant.
Stem Cells, Inc.
Mr. Jensen cites CIRM’s award to Stem Cells, Inc. as another source of a conflict. In support of this claim, Mr. Jensen’s references Bob Klein’s support of the award, as well as the fact that Irv Weissman, PhD, appeared in an ad for Proposition 71 in 2004. However, neither Mr. Klein’s support for the award nor Dr. Weissman’s support for Proposition 71 constitutes a conflict of interest. First, Mr. Klein, like any member of the public, has the right to express his views to the Board. The state’s revolving door laws do not apply to a former member of the Board who, like Mr. Klein, is not compensated for making an appearance. As for Dr. Weissman’s support for Proposition 71, nothing in state law prohibits a member of the public from seeking CIRM funding even though he supported the measure during the campaign. In fact, it would be reasonable to expect that most stem cell scientists in California (and elsewhere) supported Proposition 71. Disqualifying individuals from receiving funding because they supported the law would leave few, if any, eligible applicants.
Allegation of Conflict at Board Meeting
As further evidence of an “actual conflict”, Mr. Jensen cites another instance in 2008 in which a representative of a for-profit applicant publicly complained at a Board meeting that a member of the GWG had a conflict of interest “from a business perspective.” As provided for by CIRM’s regulations, the applicant had filed an appeal, claiming that the reviewer had a conflict of interest because he had a financial relationship with another company that was not an applicant for CIRM funding. CIRM’s legal counsel reviewed the appeal and determined that there was no conflict of interest under CIRM’s policy.
Saira Ramasastry and Laurence Elias
Mr. Jensen cites two instances in which CIRM’s hired consultants in support of his claim that CIRM has “actual conflicts of interest.” In 2010, CIRM retained a partner at Life Sciences Advisory, LLC, Saira Ramasastry, to assist CIRM’s External Advisory Panel, which completed its work in December 2010. In 2012, Sangamo BioSciences, Inc., nominated Ms. Ramasastry to serve on its Board of Directors. Although Ms. Ramasastry continued to provide some consulting services to CIRM through fiscal year 2011-12, none of her work for CIRM involved Sangamo or any CIRM program in which it was involved. Ms. Ramasastry’s services on behalf of CIRM did not create any conflict of interest. The same is true of the second instance cited by Mr. Jensen. In 2010, CIRM hired Dr. Laurence Elias, a former Geron employee and an accomplished clinical development professional, to provide CIRM with technical and regulatory input to ensure that the clinical elements of an RFA were technically complete and accurate. The concept for RFA had already been approved and as such Dr. Elias was not in any position to influence the overall scope or structure, nor did he have any role in evaluating applications. CIRM staff and Dr. Elias complied with all conflict of interest requirements. Neither contract led to an “actual conflict of interest”.
Diane Winokur
Mr. Jensen’s laundry list of “conflicts” also includes a reference to the recent appointment of Diane Winokur to serve on CIRM’s Board. Mr. Jensen quotes a representative of the ALS Association who said that Ms. Winokur will be “a tremendous asset in moving the ALS research field forward through CIRM funding." Of all the insinuations made in his blog this is perhaps the cheapest shot, taking aim at a woman who has dedicated her life to fighting a deadly disease, one that claimed the lives of her two sons. Mr. Jensen knows very well that the ALS Association does not speak for Ms. Winokur or CIRM and while we expect that Ms. Winokur will bring her expertise as an advocate for people suffering from ALS to the Board, she, like all members of CIRM’s Board, represents all Californians, not just those suffering from a particular disease. Ms. Winokur’s appointment does not create a conflict of interest.
Press Releases
Finally, Mr. Jensen cites a Board debate from 2006 involving a requirement in CIRM’s intellectual property regulations regarding press releases. Under Health and Safety Code section 125290.30(g)(1)(C), the discussion of standards does not create a conflict of interest, and the Board’s debate was enriched by the participation of members who brought their expertise and experience to bear.
Mr. Jensen says that one of the reasons why the IOM did not report any instances of conflict of interest in its report is that it did not look for any conflicts of “inappropriate behavior,” But Mr. Jensen was present in the public hearing at UC Irvine in April of 2012 when the IOM panel asked Stuart Drown, Executive Director of the Little Hoover Commission that also looked into allegations of conflict of interest at CIRM, if he could cite any actual instances. Mr. Drown said he could not. Nor did Mr. Jensen offer any when it was his turn to talk.

The view from the California Stem Cell Report:
Generally speaking, CIRM's response about “actual” conflicts of interests is a reiteration of what the California Stem Cell Report carried at the time of each incident and does not add much new to the discussion of the issues. All of the agency's earlier responses could be found in the links in the “debunking” piece. Additionally the agency confuses what are clearly actual conflicts with other instances that could involve either actual or perceived conflicts, which the IOM noted can be as deadly as the real thing. However, in the most egregious cases involving Reed and later the five medical school deans, the agency would like the public to believe that these were not serious matters because the staff detected and caught the conflicts before the grants were made.
That is like saying a burglar who was caught in the act before he escaped with his booty committed no offense.
The acts were committed by members of the CIRM board, and they were violations of conflict of interest standards. In the case of the five deans, that is why the agency voided 10 applications totaling $31 million from their five institutions. If there had been no actual conflict of interest, that would not have been necessary.
As for blaming the staff for “miscommunications,” the applications that the five deans signed were quite clear and offered them the option of having another person at their institution sign the grant proposal. Other deans on the board did not sign applications in the same round. Those applications were then handled in the normal fashion. One might ask how in the world could the head of a medical school who was also serving on the CIRM board NOT recognize a conflict of interest when asked to sign a request for cash from the board on which he served?
Regarding John Reed and his conflict of interest violation, both he and then CIRM Chairman Robert Klein have acknowledged Reed's actions were wrong. Klein, an attorney who directed the writing of the 10,000-word measure that created CIRM, advised Reed to contact CIRM staff to lobby on behalf of a grant that was approved by the board but was about to be denied by staff.(See here, here and here.)
CIRM's response contends that Reed's 6 ½ page letter was nothing more than “factual” information dealing with technical matters. That is hardly the case. In fact, Reed explicitly “emphasized” (Reed's word) that failing to comply with his letter would damage the future of the stem cell agency. Denial of the grant, he said, “will surely discourage clinical researchers from participating in the CIRM mission to advance stem cell therapies.”   
Reed's action was inappropriate, and the California Fair Political Practices Commission warned Reed about his actions. The journal Nature reported,
“California’s Fair Political Practices Commission (FPCC) decided that Burnham Institute President violated conflict-of-interest rules by writing a letter to the California Institute of Regenerative Medicine appealing a decision that an affiliate of his institute was ineligible for funding.”
The California Stem Cell Report's “debunking” piece went beyond "actual" conflicts to describe other instances where conflicts emerged. Readers can go back to the original links for all the details, but the cases of StemCells, Inc., and iPierian, Inc., are worth reviewing again. Both cases involve fund-raising efforts that ran into millions of dollars for the ballot measure campaign that created CIRM. The campaign was run by Bob Klein who later became the agency's first chairman, serving for six years and becoming something of a hallowed figure in stem cell circles. One of the principal jobs of a campaign manager is to raise the millions needed to run a successful statewide election campaign in California. It is common for members of the public to believe that major campaign contributors are rewarded later for their contributions. Whether that was the case in these instances, the reader must decide for himself or herself. But the appearance is less than salubrious for an agency that claims to have never seen an actual conflict of interest as it has handed out $32,000 an hour, 24 hours a day, seven days a week during the last six years.
The facts are that about 90 percent of the $1.7 billion awarded by the CIRM board has gone to institutions tied to present and past members of its governing board. The agency, however, does work hard to be sure legal conflicts do not arise during board action on grant applications, using a voting procedure that is so convoluted that the actual vote on nearly all applications is not even announced at board meetings. Sometimes the procedure means that only a handful of governing board members can participate in debate or vote. In the case of the five medical school deans, as the board struggled to deal with the fallout in 2007, only eight of the 29 members of the board could participate in the discussion because the rest had conflicts.
As for CIRM's comments about “insinuations” and “cheap shots” by the California Stem Cell Report, we naturally differ with that characterization. The case in point involved what the chief scientist for a patient advocate group said she expected as the result of a recent appointment to the board. The scientist's remarks were offered as example of the type of expectation and entitlement that can arise when governing board members must be picked from specific constituencies, as is the case with all 29 CIRM board members.

And as for my testimony at the IOM hearing last April, here is a link to my statement, which includes a discussion of conflicts of interest.  

1 comment:

  1. Anonymous5:18 PM

    David: I love it that you pay attention to CIRM and am glad that you point it out whenever CIRM obfuscates.

    But this is too much. CIRM- the staff, the ICOC, and the funded scientists are all human beings, and until there is a granting agency that is entirely staffed by robots, there will be potential for conflict of interest.

    Yes, I am angered that Klein and Weissman were successful in using their personal powers of persuasion to get approval for grants that they favored--whether their motives were personal or financial is irrelevant--the board should not have rewarded this bad behavior.

    Yes, I think that Reed was duped by his faculty into writing an inappropriate letter of support.

    Yes, I am alarmed that ICOC members wrote letters of support for their young faculty members- they weren't trying to short-circuit the rules, they were just doing what they always do when a young faculty member writes a grant for the NIH. Stupid, but not wicked.

    This is what conflict of interest is: conflict of interest is what happened in Texas when a cancer award was made to some friend of the administration, without any scientific review at all.

    CIRM is an experiment, and almost all the time it has done the right thing. Sure, these non-robots make mistakes, but they learn from them. None of these bad things has become chronic, and although CIRM has not always moved swiftly enough, the unfair acts have usually happened only once. Wait- there is one thing- the extraordinary petition process: the applicants seem to have learned to ignore the instructions. But that's our fault, not CIRM's- the rules clearly state what constitutes a cause for a complaint. CIRM should just tell us to shut up and read the directions.

    I'm certain that history will show that CIRM was a bold experiment that jump-started life-saving stem cell research as surely as the Susan G. Komen foundation brought to light the woefully inadequate funding for breast cancer research.

    I'm not asking you to ease up- I'm just asking you to put CIRM into perspective- by writing about the good as well as the bad.


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