1. Federal funding: Fasten your seatbelts, it's going to be a bumpy ride.
Congress has pushed the date of the "sequester" off another two months, delaying the prospect of automatic 8.2 percent cuts in the budgets of NIH, FDA, and other federal science programs. But a sequester (or other cuts) could still happen. Consider that current funding for these programs expires in March, the FY14 budgets are still being drafted, and there will likely be a fight over the debt ceiling. Advocates need to keep making noise to make a compelling case for the critical importance of medical research. The health of our citizens and the economic and fiscal health of the nation are at stake. Resources are available on our Sequestration Station website; also check out our Time Equals Lives social media campaign, where you can contribute your story to show our leaders why medical research matters, because we will all be patients eventually.
2. FDA: Recalibrating the benefit-risk equation.
Patient groups have been saying for years that people living with a disease are often willing to accept more risk than the FDA is generally willing to tolerate in a new product. Well, now the agency can do something about it. In 2012, the latest reauthorization of PDUFA created a new "Patient-Focused Drug Development" initiative at the FDA, which allows the FDA to formally consult with patients -- initially in 20 disease areas -- about what their priorities are and what tradeoffs they are willing to accept. It may not sound revolutionary, but it could represent the beginning of a paradigm shift in the regulatory process if they get the process right, and if we don't get bogged down in fighting over what the 20 disease areas are. This will be an important initiative to track and be active in this year, and an important area for the FDA to focus on across its centers.
By the way, we heard at Partnering for Cures that nobody thanks the FDA -- so here we go! Way to go, FDA, on a second year in a row of 30-plus new drug approvals. If they do it again in 2013, is it a trend?
Saying thank you to FDA's Janet Woodcock
3. Financial innovation: Attack of the megafund.
In October 2012, MIT finance professor Andrew Lo and colleagues proposed creation of a $30 billion "megafund" to bridge the translational research-finance gap by using financial engineering to securitize a highly diversified portfolio of therapies in development, an idea FasterCures got a preview of at its Financial Innovations Lab in July 2011. The model securitizes a portfolio of research assets as collateral to raise funds in the capital markets using a mix of debt and equity that appeal to a variety of investors' risk-reward ratios. Is this the kind of large-scale solution required for the big problem of financing risky research, particularly at the early stages? Lo plans a conference in 2013 to further develop the idea. Stay tuned for more work in this area by FasterCures and the Milken Institute in 2013, because this is one of the issues we are hearing the most consternation about.
4. Reimbursement: Can value drive innovation?
Concerns in the pharma industry about the impact of reimbursement on their upstream R&D strategies are escalating, as efforts to rein in health-care costs are gaining steam. But do medical progress and the quality of care have to be sacrificed on the altar of cost-cutting? We heard some interesting discussion in 2012 from former pharma exec Frank Douglas and his new Austen BioInnovation Institute in Akron about the concept of "value-driven engineering" in medical devices, based on the principles of clinical utility, reduced complexity, and cost savings and efficiency. Douglas believes this framework can be applied to drug development as well. Can we shorten the time from molecule to hu(man) to ultimately drive down costs for payers? Will a focus on value be an innovation killer, as some fear, or can it be a disruptive driver for companies to tackle risky areas of high unmet need and first-in-class therapies? What is the methodology for deciding value? Where do patients fit into the equation? We look forward to more broad-based discussions of -- and hopefully more answers to -- these critical issues in 2013, as reimbursement could be our next cliff, if we survive the fiscal one.
5. Venture philanthropy: Playing in the major leagues.
FasterCures has been tracking and supporting the rise of venture philanthropy in medical research for almost a decade, and these strategic, patient-driven research funders have hit the big leagues and gotten the attention of the large pharma companies. Small companies have found them valuable sources of seed capital and other non-financial assets for some time, but large pharma has been slower to understand what they bring to the table. 2012 saw the Cystic Fibrosis Foundation (fresh off a big success investing in Vertex's newly-approved drug Kalydeco) invest $58 million in Pfizer's research into therapies targeting the most common CF subtype (yes, you read that right -- the foundation is funding Pfizer), and Sanofi awarded $300,000 to a team of patient groups to create a cross-disease registry to accelerate translational research. Companies like Merck Serono and Celgene are working with nonprofits like the National MS Society and the Leukemia and Lymphoma Society as "talent scouts" of sorts to identify promising early-stage research. As foundation head Bonnie Addario advised a company CEO at Partnering for Cures in November, "Put us on your boards -- we put you on ours!" We call that speaking truth to power.
6. Academic research: Let's see you do that again.
Industry and investors are becoming increasingly frustrated with the lack of reproducibility of positive results from academic science published in peer-reviewed journals. In 2012, Amgen could not reproduce the results of 47 out of 53 so-called "landmark" oncology studies, and in 2011 Bayer discontinued 65 percent of its target validation projects when its results did not match published experiments. Some patient groups, like the ALS Therapy Development Institute and the Chordoma Foundation, have made replication of published results and validation of research products a core piece of their missions. Some investors are funding their own "killer experiments" before making investment decisions, and efforts like Science Exchange's Reproducibility Initiative are cropping up to find ways to systematically address the disincentives for academic researchers to validate their findings. Expect this debate to get louder in 2013 -- and hopefully coalesce around some productive solutions.
7. Data standards: Coming soon to a therapeutic area near you.
We hear over and over again that medical research desperately needs standards for collecting and analyzing data, but it's always seemed like a bite too big to chew. But the Critical Path Institute and CDISC are stepping up to the plate with CFAST, the Coalition for the Advancement of Standards and Therapies, in partnership with the FDA and the new industry consortium TransCelerate. We first heard about it at Partnering for Cures 2011, and it formally launched in October 2012, but it already has standards in seven therapeutic areas (out of 55 targeted) in various states of development. Watch for accelerated progress in 2013.
8. The other translation gap: Turning outputs into outcomes.
FasterCures has spent a lot of time focusing on the "first translation gap," between basic scientific discoveries and research in humans subjects; somewhat outside our scope has been "T2," the gap between approval of a treatment and its adoption into widespread use to improve patient outcomes, which can take as long as the R&D process. Many others have analyzed this problem, but the ImproveCareNow network has gone from analysis to action, creating a rapid learning system that is speeding the adoption of evidence-based care practices for kids with Crohn's disease and ulcerative colitis at almost 50 care centers across the country and improving their health dramatically. The Kauffman Foundation is working to scale and replicate their success through its Health Network Trust initiative. We hope 2013 will see this model launched in other disease areas.
9. Collaboration: Writing the playbook.
There now seems to be broad acceptance of the idea that collaboration among R&D stakeholders (government, academia, industry, nonprofits) is required if we are going to make progress in an increasingly complex scientific and business environment. There are many experiments in collaboration going on, and many successful outcomes that can be highlighted. It is time for more systematic analysis of what's working and what's not. While these efforts vary widely depending on the goals and the collaborators, can we draw some common lessons about, for example, what are fertile areas for collaboration, what one should look for in partners, what are the pitfalls to avoid? After all, as Luke Timmerman of Xconomy wrote recently, what we're after isn't collaboration for its own sake, it's a "creative rethinking of the biomedical R&D continuum," and "while those [collaborative] efforts are encouraging, this really should be a national conversation that involves a whole lot more players." Will 2013 be the year we start trying to know what we know, and perhaps even start redrawing that linear R&D pipeline we all know so well?
10. Innovation: Who's outside the box (you tell us).
While there's no shortage of brilliant scientists and discoveries in medical research, it can be notoriously hard to move them forward in the expensive environments of academia and industry, where risk is not necessarily rewarded. We are seeing more efforts to try to bust out of this box in ways that are more common in other fields. Philanthropist Peter Thiel, who started out by giving young people $100,000 to skip college and work on their ideas, has established Breakout Labs to fund early-stage companies with radical ideas. The National Institutes of Health is getting into the action with its "skip the post-doc" Early Independence Awards to help free exceptional young minds from the academic treadmill. Jimmy Lin's Rare Genomics Institute is crowdfunding genomic sequencing for patients with rare diseases -- and there's much discussion about crowdfunding's utility in life sciences. Crowdsourcing is gaining traction in life sciences, from FoldIt's online protein folding games to Transparency Life Sciences' crowdsourced clinical study design. Who will be redefining "the box" in 2013? You tell us -- send us your ideas at email@example.com.