A serious disease or condition is “associated with morbidity that has substantial impact on day-to-day functioning” (see 21 CFR § 312.300(b)(1)). A life-threatening condition is a disease or condition “where the likelihood of death is high unless the course of the disease is interrupted . . . and . . . with potentially fatal outcomes, where the end point of clinical trial analysis is survival” (see 21 CFR 312.81(a)). For all of these expedited programs, the applicant must also demonstrate the requisite level of evidence to support the safety and effectiveness of the product at a population level.FDA has previously granted expedited program designations to therapies for public health emergencies.

It remains unclear how much guidance FDA will provide given the Congressional intent for the Agency to be hands-off.Determining Eligibility for “Right to Try” UseUnder the new law, for a patient to eligible for “Right to Try” use, s/he must have:Been diagnosed with a severely-debilitating or life-threatening disease as defined at 21 C.F.R. § 312.81;Exhausted approved treatment options and is unable to participate in a clinical trial involving the particular investigational drug (this must be certified to by a qualifying physician); andProvided written informed consent to the physician regarding the particular investigational drug.It is not clear whether the sponsor or the physician is required to document either the certification regarding patient eligibility or the informed consent. It is also not clear how much information the sponsor should provide to the physician in order for that subject to be truly informed about the potential risks and benefits of the investigational drug.For a particular investigational drug to be eligible, it must:Have completed a Phase 1 study (as described in 21 C.F.R. § 312.21);Have not been approved or licensed for any use;Be subject to a filed New Drug Application (NDA) or Biologics License Application (BLA) ; or be under investigation in a clinical trial that is both “intended to form the primary

r stakeholders seeking Medicare coverage, it does provide a clearer idea of CMS’s expectations when reviewing a request for a NCD when CED is an option. As in the past, interested parties are encouraged to meet with CMS’s Coverage and Analysis Group and to maintain a dialogue with the agency throughout the process, to exchange ideas and to fine-tune the proposed clinical trial in order to reach a consensus with CMS.ENDNOTES[1] “Guidance for the Public, Industry, and CMS Staff: Coverage with Evidence Development,” Document Issued on November 20, 2014, available at: http://www.cms.gov/medicare-coverage-database/details/medicare-coverage-document-details.aspx?MCDId=27[2] “National Coverage Determinations with Data Collection as a Condition of Coverage: Coverage with Evidence Development,” available at: http://www.cms.gov/Medicare/Coverage/Coverage-with-Evidence-Development/index.html[3] CMS may make an exception “if the disease or condition being studied is life threatening as defined in 21 CFR §312.81(a) and the patient has no other viable treatment options.”

Where appropriate, the clinical research study is not designed to exclusively test toxicity or disease pathophysiology in healthy individuals. Trials of all medical technologies measuring therapeutic outcomes as one of the objectives may be exempt from this standard only if the disease or condition being studied is life threatening as defined in 21 C.F.R. § 312.81(a), and the patient has no other viable treatment options. The study is registered on the ClinicalTrials.gov website and/or the Registry of Patient Registries by the principal sponsor/investigator prior to the enrollment of the first study subject.