Guidance on Continuing
Evidence Generation
Adopted by the Board: Oct 28, 2026. Applies prospectively to submissions received on or after Oct 28, 2026.
1. Purpose and principle
Montana Senate Bill 535 (2025), codified at Title 50, chapter 12, MCA (the “Act”), creates an experimental treatment access pathway, not an exemption from evidence generation. The Board expects every treatment it approves for patient use to contribute to the evidence base on its safety, and where feasible and appropriate its effectiveness. This guidance states how applicants demonstrate that commitment and how the Board evaluates it.
The Belmont Report distinguishes medical practice, “interventions that are designed solely to enhance the well-being of an individual patient or client and that have a reasonable expectation of success,” from research, which is “designed to test an hypothesis, permit conclusions to be drawn, and thereby to develop or contribute to generalizable knowledge.” [1] Treatment under the Act is practice, not research: each patient is treated for that patient’s benefit, under a physician’s judgment and the patient’s informed consent. But the Belmont Report also addresses innovative practice directly [2]:
“When a clinician departs in a significant way from standard or accepted practice, the innovation does not, in and of itself, constitute research. The fact that a procedure is ‘experimental,’ in the sense of new, untested or different, does not automatically place it in the category of research. Radically new procedures of this description should, however, be made the object of formal research at an early stage in order to determine whether they are safe and effective. Thus, it is the responsibility of medical practice committees, for example, to insist that a major innovation be incorporated into a formal research project.”
The Board takes up that responsibility. Under the Act, innovative treatments reach patients through treatment protocols submitted by an applicant who is typically the IP holder of the treatment, administered by treating physicians exercising independent judgment for each patient. The Board places the evidence-generation responsibility on the party that controls and develops the treatment protocol; the treatment decision remains, in every case, the clinician’s and the patient’s. This guidance is the Board’s implementation of that responsibility, proportionate to the oversight each treatment already receives.
The Board’s review under this guidance is directed to patient safety, informed consent, and the adequacy of continuing evidence generation. It does not authorize denial or restriction of access based on the potential for diffuse social harms. Where risks to third parties are relevant, they must be material and directly connected to the proposed treatment.
2. Requirement
Every submission must demonstrate a continuing evidence-generation framework for the proposed treatment: how safety and outcome information will be systematically collected, reviewed, and reported while the treatment is offered. The applicant describes the framework in its submission. At approval it becomes a condition of the approval; the Board may adjust it as evidence accumulates. The required showing scales with the degree of independent research oversight the treatment already receives, as set out in Section 3. Nothing in this guidance changes the adverse-event reporting obligations that apply to every approval. [3]
Development toward approval. Each submission also states the treatment’s status in federal development, including any investigational new drug application (IND) or investigational device exemption (IDE) and its status, and the applicant’s plan for further clinical development toward marketing authorization or, where there is no such plan, the reasons. The Board takes this into account in setting and reviewing the framework under Section 3.
The Board does not approve a treatment involving a product that (a) is subject to an FDA clinical hold relevant to the proposed use, (b) was the subject of an investigational application withdrawn or terminated due to a safety concern, or (c) has been evaluated, for a use relevant to the proposed use, in one or more adequate and well-controlled clinical trials whose results, considered as a whole, either exclude a clinically meaningful benefit compared with placebo or no treatment or demonstrate net harm. A trial that did not detect a statistically significant benefit but was not adequately powered to exclude a clinically meaningful benefit does not by itself require exclusion under (c); the Board shall instead weigh such results in the risk-benefit analysis under ARM 37.106.3316(6)(a)(iii), and they shall be disclosed in informed consent. A treatment that has shown efficacy, but less than that of standard of care, is not excluded on that ground where the risk-benefit analysis under ARM 37.106.3316(6)(a)(iii) demonstrates a reasonable safety profile and the comparison with standard of care is disclosed in informed consent.
3. Satisfying the requirement
The experience of patients treated under the Act is itself part of the evidence base. Every approval therefore includes a prospective monitoring framework for those patients, specifying defined outcome measures, systematic adverse-event capture, a follow-up schedule, and stopping criteria, reviewed and approved by the Board and fixed as conditions of approval. Its intensity is proportional to the remaining uncertainty about the treatment’s risks and benefits in the population to be treated: it may lighten as knowledge accumulates, and deepens where a treatment is extended to populations or uses in which it is untested.
(a) Active FDA research oversight. Where an IND or IDE is in effect for the treatment, the framework will likely not exceed existing federal and state reporting obligations, unless the Board determines otherwise.
(b) Qualifying regulatory authority. The same applies where an equivalent authorization, registered clinical study, or pharmacovigilance obligation is in effect under a WHO Listed Authority (WLA), [4] or another regulatory authority the Board determines maintains substantially equivalent standards for data quality, monitoring, and patient protection.
(c) Where neither (a) nor (b) applies, one of the two forms of evidence generation applies:
Evidence Generation
Adopted by the Board: Oct 28, 2026. Applies prospectively to submissions received on or after Oct 28, 2026.
1. Purpose and principle
Montana Senate Bill 535 (2025), codified at Title 50, chapter 12, MCA (the “Act”), creates an experimental treatment access pathway, not an exemption from evidence generation. The Board expects every treatment it approves for patient use to contribute to the evidence base on its safety, and where feasible and appropriate its effectiveness. This guidance states how applicants demonstrate that commitment and how the Board evaluates it.
The Belmont Report distinguishes medical practice, “interventions that are designed solely to enhance the well-being of an individual patient or client and that have a reasonable expectation of success,” from research, which is “designed to test an hypothesis, permit conclusions to be drawn, and thereby to develop or contribute to generalizable knowledge.” [1] Treatment under the Act is practice, not research: each patient is treated for that patient’s benefit, under a physician’s judgment and the patient’s informed consent. But the Belmont Report also addresses innovative practice directly [2]:
“When a clinician departs in a significant way from standard or accepted practice, the innovation does not, in and of itself, constitute research. The fact that a procedure is ‘experimental,’ in the sense of new, untested or different, does not automatically place it in the category of research. Radically new procedures of this description should, however, be made the object of formal research at an early stage in order to determine whether they are safe and effective. Thus, it is the responsibility of medical practice committees, for example, to insist that a major innovation be incorporated into a formal research project.”
The Board takes up that responsibility. Under the Act, innovative treatments reach patients through treatment protocols submitted by an applicant who is typically the IP holder of the treatment, administered by treating physicians exercising independent judgment for each patient. The Board places the evidence-generation responsibility on the party that controls and develops the treatment protocol; the treatment decision remains, in every case, the clinician’s and the patient’s. This guidance is the Board’s implementation of that responsibility, proportionate to the oversight each treatment already receives.
The Board’s review under this guidance is directed to patient safety, informed consent, and the adequacy of continuing evidence generation. It does not authorize denial or restriction of access based on the potential for diffuse social harms. Where risks to third parties are relevant, they must be material and directly connected to the proposed treatment.
2. Requirement
Every submission must demonstrate a continuing evidence-generation framework for the proposed treatment: how safety and outcome information will be systematically collected, reviewed, and reported while the treatment is offered. The applicant describes the framework in its submission. At approval it becomes a condition of the approval; the Board may adjust it as evidence accumulates. The required showing scales with the degree of independent research oversight the treatment already receives, as set out in Section 3. Nothing in this guidance changes the adverse-event reporting obligations that apply to every approval. [3]
Development toward approval. Each submission also states the treatment’s status in federal development, including any investigational new drug application (IND) or investigational device exemption (IDE) and its status, and the applicant’s plan for further clinical development toward marketing authorization or, where there is no such plan, the reasons. The Board takes this into account in setting and reviewing the framework under Section 3.
The Board does not approve a treatment involving a product that (a) is subject to an FDA clinical hold relevant to the proposed use, (b) was the subject of an investigational application withdrawn or terminated due to a safety concern, or (c) has been evaluated, for a use relevant to the proposed use, in one or more adequate and well-controlled clinical trials whose results, considered as a whole, either exclude a clinically meaningful benefit compared with placebo or no treatment or demonstrate net harm. A trial that did not detect a statistically significant benefit but was not adequately powered to exclude a clinically meaningful benefit does not by itself require exclusion under (c); the Board shall instead weigh such results in the risk-benefit analysis under ARM 37.106.3316(6)(a)(iii), and they shall be disclosed in informed consent. A treatment that has shown efficacy, but less than that of standard of care, is not excluded on that ground where the risk-benefit analysis under ARM 37.106.3316(6)(a)(iii) demonstrates a reasonable safety profile and the comparison with standard of care is disclosed in informed consent.
3. Satisfying the requirement
The experience of patients treated under the Act is itself part of the evidence base. Every approval therefore includes a prospective monitoring framework for those patients, specifying defined outcome measures, systematic adverse-event capture, a follow-up schedule, and stopping criteria, reviewed and approved by the Board and fixed as conditions of approval. Its intensity is proportional to the remaining uncertainty about the treatment’s risks and benefits in the population to be treated: it may lighten as knowledge accumulates, and deepens where a treatment is extended to populations or uses in which it is untested.
(a) Active FDA research oversight. Where an IND or IDE is in effect for the treatment, the framework will likely not exceed existing federal and state reporting obligations, unless the Board determines otherwise.
(b) Qualifying regulatory authority. The same applies where an equivalent authorization, registered clinical study, or pharmacovigilance obligation is in effect under a WHO Listed Authority (WLA), [4] or another regulatory authority the Board determines maintains substantially equivalent standards for data quality, monitoring, and patient protection.
(c) Where neither (a) nor (b) applies, one of the two forms of evidence generation applies:
i) IRB-reviewed research. Where the applicant’s evidence-generation activity constitutes human-subjects research under federal law, the applicant conducts that activity under a research protocol approved and continuingly reviewed by a registered institutional review board. The treatment itself remains treatment under the Act.
ii) ETRB-approved monitoring framework. Where the evidence-generation activity does not constitute human-subjects research under federal law, the framework is maintained under the Board’s review alone and must meet evidence-generation standards equivalent to or higher than those of recognized regulatory authorities, or medical centers recognized as leading in the field relevant to the treatment.
ii) ETRB-approved monitoring framework. Where the evidence-generation activity does not constitute human-subjects research under federal law, the framework is maintained under the Board’s review alone and must meet evidence-generation standards equivalent to or higher than those of recognized regulatory authorities, or medical centers recognized as leading in the field relevant to the treatment.
4. Transparency
Safety and outcome data collected under this guidance flow into the Board’s monthly adverse-event review, its consolidated quarterly safety outcome reports, and its annual public report of aggregate, de-identified results (ARM 37.106.3316(6)(c)). The annual report identifies, in aggregate, the number of approvals relying on each route under Section 3.
5. Relationship to existing documents
This guidance applies prospectively and does not modify existing approvals or agreements. It is implemented through the Board’s submission documents as in effect at the time. It is a companion to, and does not modify, the Guidance on Resolving Eligibility Ambiguities.
[1] National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, The Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research (April 18, 1979), Part A (“Boundaries Between Practice and Research”).
[2] Id., Part A.
[3] Adverse-event reporting obligations under the applicable submission agreement; ARM 37.106.3317(1), (4) (ETC reporting to the department and the Board).
[4] World Health Organization, WHO Listed Authorities (WLA): regulatory authorities designated by WHO following performance evaluation against the Global Benchmarking Tool.