|Brainstorming session at the alpha clinics workshop in November 2012|
CIRM has already described how the Alpha Clinics concept was conceived and organized in a whitepaper drafted after consultation with stakeholders (that whitepaper is on our website). Nonetheless, we can’t pass up this opportunity to more closely examine the unique role of this proposed clinical network, and how it can complement resources that currently exist.
An important question is whether the number of clinical trials for investigational stem cell products justifies the expenditure of establishing a new clinical network with this focus. Is there a trend for growth? The Nature Medicine article reprinted a graph showing robust and continuous activity in investigational cell therapies during the past decade—with around 60-80 Investigational New Drug or IND submissions filed each year from 2003 to 2011. (IND registration is a program where the FDA gives researchers permission to ship an experimental drug across state lines as part of a clinical trial.) Most of these were minimally manipulated products such as blood and blood stem cell products.
What is striking is that we are now seeing a wave of new activity, increasing clinical testing for a much wider variety of investigative stem cell-based products, for a much broader range of disease indications. The technologies are becoming more complex, employing gene modification or coming from novel pluripotent cell types such as embryonic stem cells. Clinicaltrials.gov data over the past decade support this conclusion.
Manufacturing, regulatory and clinical considerations for this new class of stem cell products carry new challenges. So does ensuring that the public is educated about what constitutes a bona fide stem cell “therapy”, and the potential risks and benefits of participating in clinical trials.
One might ask—aren’t there already clinical networks in place with sufficient know-how, focus, and resources to efficiently and effectively overcome these obstacles? The NIH, for instance, supports many clinical networks. One of these—the NHLBI’s PACT program-- is specifically designed to advance cell therapies, including stem cell products. PACT focuses on the manufacturing and process development of cell products for disease indications related to NHLBI’s mission, as well as for areas of shared interest with other defined NIH-funded investigators. In some cases, these missions are compatible with those of the Alpha Clinics. Thus when possible, leveraging PACT resources for process development and cell manufacturing could advance the mutual objectives of the two networks.
CTSAs also may support Alpha Clinics activity, by, for instance, collaborating on efforts to establish shared IRBs and standing master agreements. As a model, CTSAs have already forged partnerships with a variety of specialized clinical networks, including NeuroNext.
Despite the existence of such resources, it’s hard to ignore the fact that clinical networks possessing a continuous and robust source of know-how for testing of stem cell therapies in humans are few and far between. The few that exist mostly focus on specific disease areas.
Clearly there is a need for more resources. Researchers we asked pointed to the many difficulties they have faced, in recruiting for trials, regulatory affairs, obtaining reimbursement for their products, effectively providing information to patients, and educating people about what it means to be a subject in a “first in human” clinical trial. As we found in a “gap analysis” conducted at workshop held last November—the list of gaps is a long one.
Stakeholders participating in the workshop, which included patient advocates, investigators from academia and industry, clinicians, regulatory and health care economic consultants, and others, from within and outside of California, were very enthusiastic about the possibility of creating a clinical network and sites that would help address these challenges. They believed the Alpha Clinics network could accelerate stem cell therapies, build efficiencies, and discourage stem cell tourism, during the next five years and beyond.
It should be noted that most of the gaps identified in the workshop and site visits will only be encountered by investigators nearing or holding Investigational New Drug (IND) registration, which allows them to begin a clinical trial. These gaps would not likely be identified as concerns by the larger community of translational researchers, many of who are not contemplating clinical trials for many years.
A final musing—it is interesting to consider what role “training”, in the conventional sense of the word, will play in the Alpha Clinics network. Who will provide expertise for training in a clinical arena that, in many respects, is still in its infancy? In the purest sense of the word, “training” connotes the unidirectional transfer of information from a teacher to a student. While mentoring and eventually more formalized training processes will certainly be important elements of this initiative, we envision that the benefits of network learning will be more powerful at this stage.
CIRM’s vision is to build a unique and valuable storehouse of information, data, and expertise. The Alpha Stem Cell Clinics Network will use a network-based approach for simultaneously concentrating and growing the necessary research, regulatory, manufacturing, and clinical expertise in this arena. This accelerated learning approach will take hold when all members of the network share information and data, so that each member can benefit from the experiences of others. The sharing of knowledge within the network, and with outside entities and networks, will elevate the entire field. It will yield better clinical trial design, accelerated approval of high quality treatments, and data and know-how to inform regulatory and reimbursement decisions. Most importantly, a wider range of treatment options and more reliable information will become available for people with incurable diseases and injuries.
That’s not just good for the researchers, it’s good for the patients.