Early Access & Compassionate use, when should drugs be available?

To be available for patients, a medicine must get an authorization to go to market (so called market authorization) from relevant authorities (e.g. FDA in the US or EMA in the EU). Exceptionally, a medicine could be made available before getting its market authorization under specific conditions thus defining the Early or Expanded Access/Compassionate Use.

Of note, there are generally and classically three phases of experimentation/trials:

· Phase 1: initial small-scale experimentation on humans to see how the drug is absorbed and whether there are initial side effects of increasing the dose (Toxic doses to animals have been already determined in animal trials)

· Phase 2: assesses the effectiveness of the medicine in patients, as well as common short-term side effects

· Phase 3: provides statistically robust proof of effectiveness and often involve thousands of patients and clinical trial sites around the world.

In some cases, some patients have exhausted all available alternatives for treatment and have no other solutions afterwards. In these cases, they could enroll in ongoing clinical trials. Sometimes, some patients do not qualify or are not eligible to join these trials since clinical trials have a set of criteria that patients should have/meet to be part of the trial. In this particular case, comes the role of early access to treatment and these patients can benefit from experimental medicines in development outside the settings of clinical trials but still under strong control of their physicians.

In the US, there are regulations for Compassionate use/Expanded access. Under these regulations, the U.S. Food and Drug Administration (FDA) permits a company to provide an unapproved drug to a patient under the following conditions:

· The patient has a serious or life-threatening condition

· The patient is not (able to be) enrolled in its clinical trials

· The company must be willing to provide the drug

· The company gets permission from the FDA before proceeding.

In the EU, similar regulations exist, with more or less smooth applicability. For example, in France, the latest reform now calls the French expanded access mechanism (formerly known as Temporary Authorization of Use or ATU) as either Early or compassionate access. For both, the following conditions are required:

· The patient has a serious or life-threatening condition

· The patient is not (able to be) enrolled in its clinical trials

· Safety data are provided

· Presumption of efficacy

· Presumption of innovation

Research shows that new medicines become available through the ATU mechanism in France roughly 210 days earlier than they otherwise would become available.

The application for early access in France is done by physicians. Once accepted by the French health authorities, the (experimental) medicine is imported and the statutory health insurance pays for the patient who gets it free of charge.

Similar mechanisms/programs exist in other EU countries (e.g. Italy, Spain, The Netherlands, etc.).