Risk vs. Access: new standards for evidence for evaluating regenerative medicines
New policies adopted by the US are challenging what counts as sufficient evidence for approving new therapies. There is currently a shift from relying on data derived from the clinical trial process in favour ofalternative forms of evidence. These new policies may speed up the approval process for regenerative medicines, provide more access to patients and reduce barriers to stem cell research. However, policy makers should also consider the risks, responsibilities and biases that may come with less stringent evaluation.
What questions & challenges are raised?
Over the past few decades evidence to support the approval of new medical treatments in the United States has typically come from clinical trials and other rigorously proven methods. Clinical trial data allows clinicians, researchers and governing bodies to measure how effective a treatment is, determine possible risks and side effects, and see how the treatment compares to other available treatments. Patients have generally had limited access to unapproved treatments because there could be big risks and little, if any, benefit. However, these practices are changing. There are many criticisms that the evidence-based clinical trial system is slow, expensive, laborious and isn’t appropriate for regenerative medicines (RMs). As such, policy makers are interested in changing the way RMs are evaluated. Social and political pressures are leading to new policies, such as the 21st Century Cures Act (CCA), that dramatically shift prior standards for what qualifies as evidence to approve new medical treatments. Dr Linda Hogle from the Department of Medical History and Bioethics at the University of Wisconsin Madison has written a commentary discussing this substantial shift in standards and draws parallels to other legislation, including Right-To-Try (RTT) laws aimed at increasing patients’ access to unapproved medical treatments. Dr Hogle cautions that these new policies may erode the standards for safety and effectiveness that were established by the rigorous and hypothesis-driven clinical trial system in the late 20th century.
What points are discussed?
The general trend noted by Dr Hogle is that new regulations (both previously passed and currently proposed) appear to weaken established criteria for what kind and quality of evidence is considered when determining the safety and efficacy of new medical treatments. By walking the reader through several aspects of the CCA and RTT laws, Dr Hogle points out that these pieces of legislation permit assessment of RM treatments using new forms of data that may be beneficial, but are also questionable. A few kinds of evidence that the CCA permits for the evaluation of new RMs include: observational data (such as a patient’s symptoms and mental state), indirect measures such as biomarker data, data from non-peer reviewed journal articles, data-mining of registries and medical records (to find patterns among patients), and associative and correlation analyses. Parts of the CCA also include the use of patient-collected evidence to assess the impact of treatments on patients’ quality of life. ‘Patient experience data’ and ‘real-world evidence’ are types of patient-collected data that respectively document how patients feel treatments are working and how reasonable it is to integrate a treatment into real living conditions. These data might be collected in diverse and innovative ways, such as through social media or smart phone applications. While the aim of these regulations is to gather a wider spectrum of data to evaluate new RM treatments, there are several notable concerns that Dr Hogle raises regarding elevating the impact and value of these new forms of evidence. The first being that RMs are very complex in nature; they often have multiple components, uncertain efficacies and side effects, large safety risks and unknown long-term effects. Another concern is deciding how much influence patients’ perceived effectiveness of treatments should have compared to measured outcomes of a clinical test, which may not agree. When it comes to collecting ‘real-world evidence’, there can be many problems encountered as to how the data will be collected and analysed. Data that is now permitted based upon personal accounts and experiences can be inherently biased and has similarities to testimonials used to advertise unapproved RM treatments. One last and large concern is that health care providers and health insurers generally want proof treatments work before they pay to provide them to patients. It is still not certain how treatments that are approved but don’t have a proven effect will be provided or paid for.
What insight does this give for stem cell policies?
In her discussion, Dr Hogle begins by pointing out that societies’ definition of what counts as evidence is always changing and that, “Research governance has always been as much about power and persuasion as about matters of fact”. Although there are valid reasons to consider alternative forms of evidence other than just clinical study data, the policies being adopted open up the opportunity for greater subjectivity when evaluating new therapeutics. Substantial questions remain about how much value is placed on alternative evidence, particularly with considerations to how it is collected and from whom it comes. Importantly, policy makers need to evaluate who benefits from policies that elevate alternative evidence for the approval of new treatments and who will bear the risks. New policies may aim to expedite patient access to novel regenerative medicines; however, to protect patients, it is prudent to balance expediency with rigour.