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10 trends

In recent years we’ve seen efforts to streamline regulatory and reimbursement pathways as a way to optimize patient access to acutely needed drugs. These efforts address arguments that the regulatory process isn’t fast enough or innovative enough to meet the needs of today’s patients, however they are generating controversy and push-back from industry leaders.

RTT laws for the terminally ill

State right-to-try (RTT) laws, aimed at giving terminally ill patients access to unapproved, experimental therapies, are sweeping the country. The first state RTT law was passed by Colorado in May 2014. Since then, some 20 states have enacted RTT laws, and a federal RTT bill, HR 3012, was introduced in the House in July 2015.

The goal of these laws is to give terminally ill patients access to vitally needed treatments. However, they remain controversial, in part because they fail to address patient welfare and public health, and because they create potential conflict between federal and state laws. A recent Health Affairs op-ed notes that several federal courts have concluded that the U.S. Food and Drug Administration’s (FDA) comprehensive regulatory regime governing drug products preempts state laws designed to legislate in this area. As a result, the article argues, “although these laws have created an expectation that terminally ill patients will be able to quickly access potentially life-saving treatments by being exempted from the rules of the… [FDA], this expectation is, quite simply, false.”

Last year, FDA accelerated its process for reviewing requests under its expanded access or compassionate use program in response to these laws. This is also arousing controversy around the legal and ethical implications of giving patients access to unproven medications. A NEJM article sums up the argument, saying, ‘debate will need to take into account the simple concept…that it may well not be in the interest of patients, however sick they may be, to have easier access to products that are ineffective and may actually worsen their clinical status.’

Alternative development pathways

Discussions around the proposed 21st Century Cures legislation have included alternative development pathways. These could potentially replace the traditional three-phase clinical trial paradigm as today’s technologies and science have potential to keep patients safe while accelerating access in ways not envisioned with the Gold Standard three-phase randomized clinical trial.

Two of the key elements of alternative development pathways are Adaptive Trial Designs and Master Protocols, which allow multiple drugs to be evaluated in the same trial and to identify effected and non-effected populations faster. Adaptive Trial Designs use Bayesian methodology to characterize drug efficacy more precisely and efficiently in selected populations, based upon cumulative experience. A Master Protocol allows multiple drugs to be evaluated in the same trial. An example of an adaptive trial using a Master Protocol is the I-SPY 2 trial (Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging and Molecular Analysis), from a consortium involving industry and academia, with FDA collaboration. The trial is for women with newly diagnosed locally advanced breast cancer segregated into treatment arms based upon biomarkers and other criteria. These tools are anticipated to help reduce duplicative start-up and patient recruitment processes, and positively impact time and cost.

Quintiles’ research indicates that patients are willing to use therapies developed under an accelerated pathway. This is based in part on a 2012 survey of patients living with chronic disease, which found that patients want access to new medicines sooner, and that those in greatest need are willing to accept more uncertainty about a new therapy if it offers potential to improve their health.

What does this mean for biopharma?

The art and science of ‘listening to the patient’ will become paramount as regulators call for more patient-centric risk-benefit assessment, payers require more member-centric values, and patients demand more consumer-centric messaging. Looking ahead, pressure will continue to mount to get new therapies to appropriate populations, where the risk-benefit relationship is acceptable, at the earliest possible stage. Observational data will be essential in evaluating risk-benefit.

A collaborative and networked approach will be needed, such as that used in MIT’s NEW Drug Development ParadIGmS (NEWDIGS) program, a ‘think and do’ tank that takes a systems approach to advancements aimed at enhancing capacity to deliver new, better, affordable therapeutics to the right patients, faster. Members include Bristol-Myers Squibb, GlaxoSmithKline, Johnson & Johnson, Novartis, Pfizer and Sanofi.

As regulators explore adaptive pathways, biopharma companies can shape statistical design of clinical trials and evidence generation as a whole, broadening the view of regulators to consider observational designs. Regulators are exploring data sharing and even parallel pathways with health technology assessment (HTA) agencies to gain a better-informed view of product effectiveness. Biopharma companies can seize this opportunity to harmonize core elements of their evidence package such as benefit-risk, while tailoring other clinical, economic, and humanistic proof points to specific decision-makers.


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