We Need 21st Century Clinical Trials to Produce 21st Century Cures

America got a gut-wrenching view of the complexities of drug development earlier this year when Josh Hardy, a 7-year-old cancer patient undergoing a bone marrow transplant, developed a life-threatening adenovirus infection that his compromised immune system couldn’t fight off.  With no other effective options, Josh’s parents and physicians turned to a small biotech company called Chimerix, which was developing an experimental antiviral drug to treat a related virus.

At first, Chimerix turned down the family’s request for the drug.  Chimerix had previously operated an “expanded access” program for patients like Josh, but had closed it two years ago to concentrate its scarce funds on completing clinical trials for another viral infection, CMV.

Chimerix eventually made its drug – CMX001 – available to Josh after facing a barrage of social media criticism, and after the FDA agreed to allow Chimerix to treat him in the context of a new small trial on patients with adenovirus.  Fortunately, the drug cleared Josh’s infection in a matter of days, and today Josh’s family is optimistic for his full recovery.

At the state level, Josh’s story has helped galvanize momentum for “Right to Try” legislation – passed in Colorado, Missouri, and Louisiana, with dozens of other states developing similar bills. In a nutshell, Right to Try legislation would allow patients with life-threatening diseases to access drugs after initial safety testing – called Phase I trials – if companies agreed to supply the drugs (and the FDA could still penalize the companies for providing non-FDA approved medicines to patients).

Right to Try advocates certainly have their hearts in the right place, and patients with terminal illnesses deserve better options.  But state legislation won’t change the underlying framework for conducting clinical trials for FDA approval – when many more patients will have access to them.

Josh’s moving story certainly underscores how difficult, expensive, and uncertain the current drug development paradigm is – and how current clinical trial protocols often don’t meet the needs of desperately ill patients. Granting expanded access to a handful of patients at a time, or even a few hundred, won’t help us attain what should be our overarching goal – slashing the time and cost required to bring important new medicines to patients.

Instead, we need to create a clinical trial process for the 21st Century, one that takes advantage of all of the technologies at our disposal to ensure that every patient has an opportunity to participate in clinical trials (if they want to) testing therapies tailored meet their specific disease state.

Take cancer. Cancer is really a catch-all term for hundreds of different diseases that are defined by aberrant cell growth and proliferation.  Beating the disease will likely entail mixing and matching complex drug cocktails that are precisely tailored to each patient’s specific tumor genome, much the way that HIV drugs are matched to different strains of the virus.

Enrolling patients in clinical trials to test targeted drugs (and drug cocktails) is a critical part of the process of unraveling cancer’s deadly complexity.  And yet, only about 3-5% of cancer patients ever enroll in cancer clinical trials and about 20 percent of cancer trials will fail to accrue enough patients to ever launch – wasting scarce resources.  Many cancer patients aren’t even aware that participating in clinical trials is even an option.

The high cost, and slow rate, of cancer clinical trial completion slows down the entire cancer research and drug discovery process.

Companies aren’t the real villains here.  They want to grant expanded access when they can, but also have to stay tightly focused on their best shot at FDA approval for a given drug indication, or run the risk of derailing or delaying research on an otherwise promising therapy.  If treating patients today delays widespread access to the drug later, it creates a real practical and ethical quandary.

However, there are promising strategies for sharply raising the number of patients aware of, and eligible for, clinical trials.  In the rare disease community, clinical trial consortiums often bring together multiple centers of excellence that share the same protocols for collecting data and testing new therapies in patients – lowering the cost of running the trials, accelerating patient recruitment, and reducing unnecessary bureaucracy.

Electronic health records (EHRs) can also be utilized to help match newly diagnosed patients with clinical trials they may be eligible for, including the latest biomarker-guided trials.  EHRs can also help raise awareness of clinical trials in populations – like minorities – where awareness of clinical trials is traditionally low.

Finally, we need to align our rapidly advancing understanding of diseases like cancer with the regulations governing drug development.  While whole genome sequencing and other technologies are leading us to “slice” cancer into ever smaller populations based on shared genomic features, many clinical trials still enroll patients based on tumor organ type (breast, cancer, etc.).  Shifting to a genomic-based framework would allow for smaller, faster, more individualized trials that could treat multiple tumor types, giving clinicians valuable treatment information that they might otherwise have to wait years after a drug’s initial approval to gain.

Regulators should also carefully reconsider the requirement for Phase III, randomized, placebo-controlled trials in an era of growing mechanistic understanding of complex chronic diseases.

Innovative clinical trial prototypes are already being deployed.  For instance, the National Cancer Institute, FDA, patients’ groups, and drug companies recently joined hands to pioneer an innovative approach to testing drugs for lung cancer, called the Lung Cancer Master Protocol or Lung-MAP.  Lung-MAP represents a “multi-drug, targeted screening approach that matches patients with promising new treatments based on their unique tumor profiles,” rather than trying to test one drug in one trial at a time and seeing who responds.

What is needed now is a national effort to overhaul an outdated clinical trial paradigm that serves too few patients at too high a cost – in dollars and lost lives.

Fortunately, there is a long-term, bipartisan effort in the House of Representatives to truly accelerate patient access to important new therapies.  The 21st Century Cures Initiative, led by Energy and Commerce Chairman Fred Upton (R, MI), and Rep. Diana DeGette (D, CO) is bringing stakeholders together to transform how America discovers, develops, and delivers new medicines.  In a Congress too often defined by partisan rancor, the 21st Century Cures Initiative is a welcome reminder that America’s policymakers can still come together to meet and solve great challenges.

Josh’s struggle is repeated thousands of times every day.  And in an era of Facebook and Twitter, every patient has a ready-made megaphone to demand better solutions when they come up against unnecessary roadblocks.

Washington, for a change, appears to be listening.

Morning Consult