Month of CIRM: Reviewing Review

Dr. Gil Sambrano, Vice President Portfolio & Review

All this month we are using our blog and social media to highlight a new chapter in CIRM’s life, thanks to the voters approving Proposition 14. We are looking back at what we have done since we were created in 2004, and also looking forward to the future. Today we take a look at our Review team.

Many people who have to drive every day don’t really think about what’s going on under the hood of their car. As long as the engine works and gets them from A to B, they’re happy. I think the same is true about CIRM’s Review team. Many people don’t really think about all the moving parts that go into reviewing a promising new stem cell therapy.

But that’s a shame, because they are really missing out on watching a truly impressive engine at work.

Just consider the simple fact that since CIRM started about 4,000 companies, groups and individuals have applied to us for funding. Just take a moment to consider that number. Four thousand. Then consider that at no time have there been more than 5 people working in the review team. That’s right. Just 5 people. And more recently there have been substantially fewer. That’s a lot of projects and not a lot of people to review them. So how do they do it? Easy. They’re brilliant.

First, as applications come in they are scrutinized to make sure they meet specific eligibility requirements; do they involve stem cells, is the application complete, is it the right stage of research, is the budget they are proposing appropriate for the work they want to do etc. If they pass that initial appraisal, they then move on to the second round, the Grants Working Group or GWG.

The GWG consists of independent scientific experts from all over the US, all over the world in fact. However, none are from California because we want to ensure there are no possible conflicts of interest. When I say experts, I do mean experts. These are among the top in their field and are highly sought after to do reviews with the National Institutes of Health etc.

Mark Noble, PhD, the Director of the Stem Cell and Regenerative Medicine Institute at the University of Rochester, is a long-time member of the GWG. He says it’s a unique group of people:

“It’s a wonderful scientific education because you come to these meetings and someone is putting in a grant on diabetes and someone’s putting in a  grant on repairing the damage to the heart or spinal cord injury or they have a device that will allow you to transplant cells better and there are people  in the room that are able to talk knowledgeably about each of these areas and understand how this plays into medicine and how it might work in terms of actual financial development and how it might work in the corporate sphere and how it fits in to unmet medical needs . I don’t know of any comparable review panels like this that have such a broad remit and bring together such a breadth of expertise which means that every review panel you come to you are getting a scientific education on all these different areas, which is great.”

The GWG reviews the projects for scientific merit: does the proposal seem plausible, does the team proposing it have the experience and expertise to do the work etc. The reviewers put in a lot of work ahead of time, not just reviewing the application, but looking at previous studies to see if the new application has evidence to support what this team hope to do, to compare it to other efforts in the same field. There are disagreements, but also a huge amount of respect for each other.

Once the GWG makes its recommendations on which projects to fund and which ones not to, the applications move to the CIRM Board, which has the final say on all funding decisions. The Board is given detailed summaries of each project, along with the recommendations of the GWG and our own CIRM Review team. But the Board is not told the identity of any of the applicants, those are kept secret to avoid even the appearance of any conflict of interest.

The Board is not required to follow the recommendations of the GWG, though they usually do. But the Board is also able to fund projects that the GWG didn’t place in the top tier of applications. They have done this on several occasions, often when the application targeted a disease or disorder that wasn’t currently part of the agency’s portfolio.

So that’s how Review works. The team, led by Dr. Gil Sambrano, does extraordinary work with little fanfare or fuss. But without them CIRM would be a far less effective agency.

The passage of Proposition 14 means we now have a chance to resume full funding of research, which means our Review team is going to be busier than ever. They have already started making changes to the application requirements. To help let researchers know what those changes are we are holding a Zoom webinar tomorrow, Thursday, at noon PST. If you would like to watch you can find it on our YouTube channel. And if you have questions you would like to ask send them to info@cirm.ca.gov

From bench to bedside – CIRM plays a vital role in accelerating science

Dr. Maria T. Millan, President & CEO of CIRM

The field of stem cell research and regenerative medicine has exploded in the last few years with new approaches to treat a wide array of diseases. Although these therapies are quite promising, they face many challenges in trying to bring them from the laboratory and into patients. But why is this? What can we do to ensure that these approaches are able to cross the finish line?

A new article published in Cell Stem Cell titled Translating Science into the Clinic: The Role of Funding Agencies takes a deeper dive into these questions and how agencies like CIRM play an active role in helping advance the science. The article was written by Dr. Maria T. Millan, President & CEO of CIRM, and Dr. Gil Sambrano, Vice President of Portfolio Development and Review at CIRM.

Although funding plays an essential role in accelerating science, it is not by itself sufficient. The article describes how CIRM has established internal processes and procedures that aim to help accelerate projects in the race to the finish line. We are going to highlight a few of these in this post, but you can read about them in full by clicking on the article link here.

One example of accelerating the most promising projects was making sure that they make important steps along the way. For potential translational awards, which “translate” basic research into clinical trials, this means having existing data to support a therapeutic approach. For pre-clinical and clinical awards, it means meeting with the Food and Drug Administration (FDA) and having an active investigational new drug (IND) approved or pre-IND, important steps that need to be taken before these treatments can be tested in humans. Both of these measures are meant to ensure that the award is successful and progress quickly.

Another important example is not just giving these projects the funding in its entirety upfront, rather, tying it to milestones that guide a project to successful completion. Through this process, projects funded by CIRM become focused on achieving clear measurable objectives, and activities that detract from those goals are not supported.

Aside from requirements and milestones tied to funding, there are other ways that CIRM helps bolster its projects.

One of these is an outreach project CIRM has implemented that identifies investigators and projects with the potential to enhance already existing projects. This increases the number of people applying to CIRM projects as well as the quality of the applications.

Another example is CIRM’s Industry Alliance Program, which facilitates partnerships between promising CIRM-funded projects and companies capable of bringing an approved therapy to market. The ultimate goal is to have therapies become available to patients, which is generally made possible through commercialization of a therapeutic product by a pharmaceutical or biotechnology company.

CIRM has also established advisory panels for its clinical and translational projects, referred to as CAPs and TAPs. They are composed of external scientific advisors with expertise that complements the project team, patient advocate advisors, and CIRM Science Officers. The advisory panel provides guidance and brings together all available resources to maximize the likelihood of achieving the project objective on an accelerated timeline.

Lastly, and most importantly, CIRM has included patient advocates and patient voices in the process to help keep the focus on patient needs. In order to accelerate therapies to the clinic, funders and scientists need input on what ultimately matters to patients. Investing effort and money on potential therapies that will have little value to patients is a delay on work that really matters. Even if there is not a cure for some of these diseases, making a significant improvement in quality of life could make a big difference to patients. There is no substitute to hearing directly from patients to understand their needs and to assess the balance of risk versus benefit. As much as science drives the process of bringing these therapies to light, patients ultimately determine its relevance.