CIRM Delays Action on Clinical Trials, Biotech Loan Changes

The California stem cell agency today said its directors would put off until their March meeting a discussion of a proposed foray into financing of clinical trials.

CIRM also said that directors would not vote this week on changes in its $500 million biotech loan program. Instead they are expected to act later on the proposal during a special telephonic meeting.

Both topics are on the agenda for this week's meeting in San Francisco, which begins on Wednesday and continues on Thursday.

In an email, Don Gibbons, CIRM's chief communications officer, said, “Chill on the (agenda) documents. The clinical RFA discussion is being put off until the March board meeting and the loan program vote will be at a special telephonic board meeting after everyone has had a chance to review the minor changes made by the finance subcommittee. Both these agenda alterations have been in the works for a few days, I just needed to verify them.”

Earlier posts (here and here) on the California Stem Cell Report have noted that CIRM had not posted an explanation of or a justification for the loan changes. CIRM also has not laid out just what is being proposed in the clinical trial venture. All of which makes it quite difficult for researchers, biotech businesses and the public to offer any sort of well-considered comment prior to board action.

The proposed loan guidelines, however, were posted today, but still missing is an explanation of why they are needed or exactly how the changes departed from the original plan.

Also posted today, under the topic of membership of a directors Scientific Issues Subcommittee, was a 12-page report on the prescreening process in use at the agency for some grant rounds. The report included a survey of 117 applicants.

The report said, in part, that “the results suggest that applicants, PreApp (preapplication) reviewers and GWG (the scientific grant review group) reviewers favor this process. The process has created an opportunity for many applicants to compete that have not previously applied to CIRM and a significant number of these have succeeded in acquiring a grant. The process allowed us to consider more proposals within a single review cycle than would have been possible using conventional review.”

Inside Stem Cell Funding: The Cost of Making a Grant

How much does it cost to give away $230 million? Something more than $173,000 or about $12,000 for each of the 14 awards in the recent disease team round from the California stem cell agency.

Those are conservative figures based on a document posted Sunday on the CIRM Web site. The report said it could have cost up to $280,000 to approve all the grants in the disease team round if the new “PreApp” review had not been in place. That figure would have climbed to $300,000 or so if you add in about $20,000 for the cost of the CIRM directors' meeting. (We have also added $20,000 to the $152,500 figure reported for PreApp disease team process).

We say our calculations are conservative because the $20,000 figure was reported several years ago, and it is not clear whether it includes all travel and meeting expenses for the directors and staff. The calculations also do not include interest expense, which would perhaps double the total cost of each grant. Interestingly, the debt financing of research makes CIRM grants much more costly to taxpayers than NIH grants.

The main point, however, of the CIRM PreApp report dealt with a staff recommendation that the process be continued in the future. The excellent, 10-page document covered nearly all the bases on the PreApp process, including comments from reviewers, applicants, staff and more. CIRM directors will consider the recommendation to continue the process at their meeting tomorrow and Thursday.

What is missing is an analysis of whether the process removes the CIRM directors, who legally have final say on grants, even further from the approval process. Already, reviewers make the de facto decisions on grants. Directors almost never overturn positive or negative decisions by reviewers. CIRM staff, however, probably made an overt decision not to even dip a toe into that sensitive area.

Here are some of the other conclusions from the report, in addition to cost savings, concerning the virtues of PreApp:

• It “encouraged many new successful applicants – more than 50% of applicants had never previously applied for a CIRM grant.”
• Several reviewers “indicated that the overall quality of applications reviewed after the PreApp process was better than without PreApp.”
• Most applicants (87 percent), when given a choice between limiting the number of applications submitted per institution and an open submission of PreApps, preferred the PreApp process.

The pre-screening process was begun about a year ago to deal with problems handling large numbers of applications. Indeed, CIRM was swamped by more than 200 applications in one round several years ago. Handling those kinds of numbers can require more than one meeting of the grant review group, whose scientist members are all from out of state. Beyond the expense, the travel time required for four meetings a year places a professional burden on reviewers.

Here is how the PreApp process works. Each initial proposal is assigned to three external reviewers, who receive electronic copies of the proposals. No meeting of the external reviewers is held, and they do not see each other's reviews. Following the external review, CIRM science officers evaluate the proposals. A CIRM review meeting is then held with attendance limited to appropriate science officers, review officers, legal staff and the president of CIRM, Alan Trounson.

According to CIRM, the proposals are “ordered according to the level of enthusiasm across all reviewers with those having a unanimous recommendation to invite on top and a unanimous recommendation not to invite at the bottom.”

CIRM said,

“The PreApps were considered and discussed taking into account any discrepancies among reviewers. For each application, the science officers took a majority vote to invite or not invite the applicant to submit a full application. The CIRM President and CIRM CSO (chief scientific officer)do not participate in the vote unless the Science Officers are at a tie.”

The report is a forthright and clear explanation of the PreApp process that should be required reading for all potential applicants. It also could serve as a model for other background information on all items on the CIRM directors' agendas.

Coming Up at CIRM: Grant Triage and More Cash for Training, Translational Research

Directors of the California stem cell agency will meet Dec. 9-10 to consider a pay increase for one of its two vice chairmen and to give away more money for training at state and community colleges.

The agenda for the meeting at Stanford University was posted yesterday on the CIRM Web site. As usual, only the sketchiest information is currently available on the matters to be considered, but more is expected to posted over the next few days.

CIRM did not specify the amount of the increase proposed for Art Torres, who has served as a vice chairman for eight months. Currently he receives a $75,000 salary for what is supposed to be a half-time job. Our impression, however, is that he putting in considerably more effort than that.

Torres, former head of the state Democratic Party and longtime state legislator, brings to the board political know-how and connections along with state government expertise that are found nowhere else at CIRM.

Duane Roth, a San Diego businessman, is the other CIRM vice chairman. He has declined a salary.

The board is expected to act on additional grants in the “Bridges” training program. The board last January put off funding some applications in the so-called tier two category because of CIRM's financial difficulties, which are now resolved through June 2011.

Grant applicants may be interested in an item dealing with conflict of interest appeals on applications. The board is scheduled to make an unspecified “correction” concerning such appeals.

Of special interest to applicants is a CIRM staff recommendation to continue the triage or pre-application process on grants. The procedure was used on the disease team round and involves initial staff and outside reviewer screening of brief grant proposals. Only those applicants who make that cut may apply for grants.

Also on tap is approval of a round of “early translational” grants and creation of a board of directors “Subcommittee on Communications with the California Public” and a “Task Force on Public Media.” The task force would be derived from the communications subcommittee.

If you have comments for the directors on these proposals, you can send them directly to CIRM at mking@cirm.ca.gov. If you would like to comment on them for the benefit of readers of the California Stem Cell Report, you may do so by clicking on the word “comments” at the end of this item. Anonymous comments are permitted.

CIRM Begins Application Triage Experiment

The California stem cell agency is moving forward on its plan to perform closed-door, staff-connected triage on grant proposals before they move into the peer review process.

John M. Simpson, stem cell project director of Consumer Watchdog of Santa Monica, Ca., reported on the action by CIRM directors on Tuesday. But he suggests an alternative that could serve CIRM's desire to reduce the number of applications on some grant rounds. Just open up the grant application process so that the public would know who is applying and hear the pros and cons on the applications.

Writing on his organization's blog, he said,

"It's our $3 billion that's being handed out. If you want our money, you ought to be willing to ask for it in public. Nothing builds more trust in a review process than having it completely transparent."

Simpson reported that Tuesday's special, teleconference board meeting failed to muster a quorum despite an attempt to set up multiple out-of-state locations for the convenience of traveling board members. Only 15 checked in. Nineteen are needed for a quorum. The full board has 29 members.

Failure to attain a quorum meant no action on the request by the International Society of Stem Cell Research for $400,000 to help finance its $1.5 million convention in San Francisco in 2010. It was the second time the board has failed to act on the request.

Here is a link to CIRM's four-page explanation of the triage proposal. The process will be applied in the $60 million basic biology round. The RFA should be posted before the end of this year with the "pre-applications" due towards the end of January.