Accelerating the commercialization of promising new cancer treatments relies on ensuring that patients — individually and collectively — are actively involved throughout research and drug development. This was the consensus of leading scientists, advocates, and government officials meeting in Washington, DC, at the first national policy forum convened by the Cancer Innovation Coalition (CIC). A collaboration of cancer stakeholder organizations and others working through a national campaign called Project Innovation — which is spearheaded by National Patient Advocate Foundation (NPAF) — the CIC aims to elevate cancer innovation to a national priority. To move cancer discovery forward, experts are calling for greater use of innovative clinical study designs, creating clinical trial networks and sharing data, and streamlining institutional and regulatory obstacles that hinder scientific discovery and drug development.
Innovation is the key to progress, but it is not happening fast enough. That is why we need new solutions to close the gap between advances the United States has made in science and technology and the regulatory and funding obstacles that are driving up costs and delaying new cancer therapy development. Through Project Innovation, stakeholders and policymakers can chart a new roadmap to bring forth promising new treatments.
Based on the insights from this meeting and other roundtables being held across the country, the CIC is developing specific recommendations for federal legislation and regulatory policies that will speed the pace of biomedical discovery in oncology. The coalition plans to announce its cancer innovation policy agenda in early 2015.
Creative Clinical Trial Designs
Cancer care is rapidly moving from a one-size-fits-all treatment approach toward personalized medicine. Meeting participants addressed the immediate need to improve the “ecosystem” of oncology research through greater use of innovative clinical study designs and master protocols to create a single clinical trials infrastructure for simultaneously testing multiple drugs.
Only one in 10 drug candidates showing promise in early studies will be approved for market by the Food and Drug Administration (FDA). Janet Woodcock — director of the FDA’s Center for Drug Evaluation and Research (CDER) — acknowledged that cancer discovery has become increasingly inefficient and expensive in the United States. It takes at least nine years for a new cancer therapy to go from discovery to approval compared with an average of two years for human immunodeficiency virus (HIV) drugs.
Because drug development is an uncertain process, a 2010 Tufts University study puts the cost of developing an innovative cancer drug at >US$1 billion (1). A priority for the CIC is to understand the major drivers behind such high costs, especially in relation to the time it takes to enroll patients in cancer clinical trials. Those costs could be lowered by such efforts as improving patient recruitment, expanding the pool of eligible candidates, and decreasing trial completion times.
Federal Initiatives: Woodcock said the FDA now accepts trial designs that use a single pivotal clinical trial — and in many cases, trials involving relatively small groups of patients for shorter durations. The agency also supports adaptive trial designs in which biomarkers (e.g., specific cells, genes, enzymes, hormones, and other measurable substances) can identify the patients who will respond best to a new drug. Master protocols could use common biomarkers to test multiple drugs concurrently. Such targeted approaches may be key to lowering drug development costs and expediting approvals, at least for patients in whom a given drug can be quickly demonstrated as an effective therapy.
Echoing Woodcock’s assessment, Meg Mooney — chief of the National Cancer Institute’s (NCI’s) clinical investigations branch — said that NCI is currently implementing a national strategy for precision medicine to sponsor a series of large-scale studies based on the molecular characteristics of specific cancers. Among such trials now under way are
- the Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trial (ALCHEMIST), which identifies early stage lung-cancer patients with specific alterations in two genes
- the Exceptional Responders Initiative, which studies molecular reasons why a small number of patients respond well to an investigational cancer agent when most others do not
- the Lung Cancer Master Protocol (Lung-MAP), which assigns patients with advanced squamous cell lung cancer to one of five different investigational drugs based in part on genetic profiles.
Some Lung-MAP cosponsors include Friends of Cancer Research, Foundation Medicine, the Foundation for the National Institutes of Health (FNIH), SWOG (formerly the Southwest Oncology Group), and five pharmaceutical companies: Amgen, AstraZeneca, Genentech, MedImmune (AstraZeneca’s global biologics R&D arm), and Pfizer.
Other Initiatives: The policy forum also addressed new ways that drug sponsors are expediting clinical testing through a “bring the protocol to patients” model, also known as P2P. One such effort is Novartis’ Simplified Institutional Review Board Process (“SIGNATURE”), in which cancer patients are tested for genetic abnormalities in their tumors and then treated with specific investigational therapies based on the tumors’ molecular “blueprints.”
Enrollment Rates Remain Low
Despite positive developments in study design, scientists and patient advocates at the policy forum painted a disturbing picture of overly restrictive eligibility criteria, patients unaware of trial availability, consent-form complexities, burdensome institutional procedures, and negative clinic environments — all of which can keep eligible patients from enrolling in cancer trials. Because of such problems (and the time and costs involved), 70% of all clinical trials now take place outside the United States (2). Even academic sponsors tend to conduct their studies internationally.
“Clinical trials should be ‘standard of care’ for cancer patients,” said Joan Schiller, a cancer researcher at the University of Texas Southwestern Medical Center. “We need to address these issues in a scientific, quantitative fashion to determine what works and what doesn’t — just like we address all clinical issues.”
One possible solution involves programs that promote shared decision-making between patients and physicians. For example, the Cancer Support Community’s (CSC’s) free, national Open to Options program, which teaches patients to ask questions of their physicians and effectively communicate their treatment goals. Vicki Kennedy (CSC’s vice president of program development and delivery) says that, in a three-year pilot program, 49% of program-trained patients discussed clinical- trial participation with their doctors, and 8% enrolled — far above the national average of 2–5%.
Barriers to Genetic Testing and Patient Access
Although regulators and scientists advocate for greater use of biomarker-driven clinical trials, experts at the policy forum raised flags about barriers to genomic testing. They pointed to major differences in the way such tests are regulated. The promise of using biomarkers in cancer trials has gotten ahead of laboratories’ ability to prove their “clinical validity” to Medicare and other payers. To address these problems, several experts called for greater real-time access to clinical records and a coordinated effort to collect clinical-outcomes data through registries of all types.
Experts also called for immediate action to address the inequities that limit patient access to innovative cancer treatments. In particular, they pointed to a practice by both Medicare and commercial health insurers to move newer cancer therapies into the highest “specialty tier” of coverage. They charge patients a percentage of the drug’s cost: 25–71%, according to recent estimates (3).
Calling that practice “a travesty,” Ted Okon (CEO of the Community Oncology Alliance) compared it with lower copays for physician services and hospitalizations, which are covered as medical benefits. Insurers cover cancer medicines taken at home as pharmacy benefits and can thus require much higher copays, even though cancer drugs have been shown to help reduce overall treatment costs. Compounding the problem, cancer patients (including those covered under the new state insurance exchanges) often don’t know whether their medications are on payer formulary lists when they sign up for coverage. That leaves many patients uncertain until it is too late to consider different insurance plans.
Cancer specialists also warned that the increasing trend of hospitals and health systems buying out physician- owned community cancer clinics is shifting cancer care to hospital outpatient departments. That restricts access for patients living in rural areas and increases costs overall. In fact, according to data from the American Society for Clinical Oncology, >1,200 community cancer care centers have closed, consolidated, or reported financial problems since 2008 (4).
“The current system is broken and involves network problems, difficulties getting access to specialists, and shifting costs of cancer medicines to patients through formulary policies,” said Lauren Barnes (a senior vice president at Avalere). “We need to discuss the total patient burden if we are going to improve access and transparency for patients.”
About the Forum And Project Innovation
Taking place on 30 September 2014, this national policy forum was the first in a series of regional forums, town halls, and workshops that the CIC is hosting around the country as part of Project Innovation. From these sessions, the group will develop a national cancer innovation policy agenda with specific recommendations for federal and state governments to accelerate delivery of promising new treatments to cancer patients. Primary funding for this initiative comes from the NPAF with additional support through research grants from Celgene Corporation, Eli Lilly, Novartis, and Pfizer.
1 Tufts Center for the Study of Drug Development. Tufts CSDD Outlook 2010. Tufts University: Boston, MA, 13 May 2010; http://csdd. tufts.edu/files/uploads/outlook-2010.pdf.
2 Glickman SW, et al. Ethical and Scientific Implications of the Globalization of Clinical Research. New Eng. J. Med. 360, 2009: 816–823.
3 2014 Forecast Series: A Conversation with Nancy Davenport-Ennis. OBRoncology 8(1) 2014; http://obroncology.com/obrgreen/article/2014- Forecast-Series-A-conversation-with-Nancy-Davenport-Ennis.
4 American Society for Clinical Oncology. Joint Statement on the President’s Budget from ASCO, Community Oncology Alliance, ION Solutions, and the US Oncology Network. The ACO Post 12 April 2013; www.ascopost.com/ViewNews.aspx?nid=2127.