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Patrick Bedford is the Senior Manager of Clinical Translation and Regulatory Affairs at CCRM. He holds a Master’s Degree in Bioethics and Health Law, and a Regulatory Affairs Certificate. Patrick has spent over 11 years applying federal regulations to emerging biotechnologies in Canada. Follow him on LinkedIN.

Do desperate times call for desperate measures in the context of early drug access mechanisms?  Regulatory agencies already recognize that they do, and there were mechanisms in place before the right-to-try movement. So, for those of us coming late to the debate, three questions remain: why were existing early access drug mechanisms inadequate; what were the options for fixing them; and, how are secondary stakeholders affected?

In the U.S., the Food and Drug Administration (FDA) already had policies to allow expanded access to novel investigational drugs, and they already recognized that there are circumstances where drugs should be able to be used widely for off label indications. These policies can be perceived as too restrictive because they rely on U.S. FDA decision-makers who apply specific criteria; however, I think the biggest concern about these pathways is that their thresholds remain subjective, opaque, and elusive. Objectivity in applying scientific expertise to evaluate chemistry and manufacturing controls (product quality), clinical safety, and clinical efficacy is regulatory armour. Despite their best efforts to make the “right” decisions, subjective benefit/risk thresholds remain the chink in the armour.

Similarly, in Canada the regulator already has long-standing policies in place to allow early access in the case of unmet clinical need for serious diseases or conditions. Health Canada does its best to apply these policies in a compassionate manner: In addition to clinical trial access mechanisms in Canada, patients have been able to obtain drugs through the Notice of Compliance with Conditions pathway, importation for personal use, and (most applicable to this discussion) the Special Access Program also known as the “SAP.” Each of these processes have been in place for over a decade. It is more difficult to say that Canadian policies suffer from the same challenges to the same extent as those in the USA, because the SAP defers the subjectivity of benefit-risk decisions to individuals and their physicians.

I suggest that this deference to patient autonomy is primarily what individual U.S. states passing “right to try” legislation aim to accomplish. This was its purpose. This assertion is supported by the basic observation that Right to Try legislation has not made the same ground in Canada as in the U.S.  I propose below another way to acknowledge the importance of patient perspectives, but before I do this, I want to highlight a key challenge to the right-to-try movement: the need for individual patients to access unapproved therapies must be balanced against two things: first, the need to protect individuals, and particularly vulnerable patients in the context of health care, from “snake oil salesmen,” (which I will not address here); and second, the need for companies to obtain data that will support market authorization and product reimbursement, which I will now briefly highlight.

Companies can and should strategically distribute their products throughout product development. Allowing compassionate access to terminally ill patients that do not meet inclusion criteria (or do meet exclusion criteria) of a carefully controlled clinical trial, for example, represents significant risks to company development, growth and success. This is because companies are required to report to the regulator any and all suspected serious adverse events from the use of their products, which includes experiences outside the clinical trial setting. Regulators take adverse event reports very seriously and consider them in risk assessments. These can contribute heavily to negative regulatory decisions or regulatory enforcement activities. Conversely, success stories outside a carefully controlled clinical trial do not heavily contribute to positive regulatory decisions. So there are risks to the company from allowing more access early in development that are not adequately balanced by benefits.

Is there a more balanced option?

The patient’s voice is what is missing from the equation. One solution was the right-to-try movement. The right-to-try movement replaces the regulator’s voice with the patient’s, which swings the pendulum quite far. A more balanced solution would balance the importance of objective regulator scientific evaluations and the need to consider patient voices in subjective benefit-risk decisions. This has been referred to as “patient input into the review process.” Allowing a system that gives patient input into the review process can help to ensure that the benefit-risk threshold decision remains appropriate. More patient input might also support other government efforts to improve regulatory transparency and openness.

This post is just one of many covering this topic as part of Signal’s second annual blog carnival about the theme Right to Try. Click here to read what other bloggers think.

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Signals accepts guest blog posts on topics relevant to stem cells and regenerative medicine, as well as submissions for its Right Turn Friday feature. See for more information. The opinions, accuracy, completeness and validity of any statements made in guest posts are the responsibility of the author only and not the editor of Signals or CCRM, publisher of Signals. The copyright of this content belongs to the author and any liability with regards to infringement of intellectual property rights remains with the author.