HTAi Blog

Policy Forum Scoping Discussion "Progressive/Adaptive Licensing & HTA"

The HTAi Policy Forum will be discussing "Progressive/adaptive licensing & HTA" at its upcoming meeting in early 2014.  As a precursor to this, the Forum held a scoping meeting at the HTAi Annual Meeting in Seoul, South Korea, where members of the Forum members met to identify key issues in this broad topic.

A summary of the discussion is provided in this blog, organized by the following themes: criteria for AL; data & assessment issues; risk management concerns; innovation considerations; post-market issues; early dialogue opportunities; stakeholder involvement; issues for devices; and legislative concerns.

All members of the Policy Forum, HTAi and other experts in this area are invited to continue the scoping discussion by providing comments, references, or other information to be considered by the Policy Forum in defining the scope of their upcoming meeting.

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Guiding questions for small group discussion

Scientific Secretariat introductory presentation

  • Criteria for AL 1 comment

    It is important to determine criteria for when (and when not) to use AL, and to identify what is needed to grant license approval at different stages in the process.

    Criteria proposed by the Forum include:

    AL may be the most appropriate where a technology:

    • Offers evidence/promise of large treatment effect and change in standard care (disruptive technologies?)
    • Address areas of unmet medical need (life threatening conditions with no treatment alternatives; ultra-orphans, rare diseases; emerging infections)

    And/or where there is:

    • Evidence of magnitude of potential impact vs. standard of care.
    • Sufficient data availability

    AL may be less appropriate for:

    • "Me too" drugs
    • Where there is limited/no data availability

    It may also be useful to establish principles for the application of AL with buy-in from HTA agencies, regulators & industry.  Such principles might include:

    • AL is a select/voluntary process
    • Clear criteria for selection, e.g., areas of high uncertainty, access to technologies is not delayed or made more restrictive
    • Access to data for demonstrating real-world effectiveness
    • Sharing of risks including costs of additional evidence required
    • A more streamlined process
    • Continual incentives for R&D in important areas of unmet need
    • Look at all new treatments/comparators in AL

    ---> QUESTIONS:

    Is there a need for criteria or principles in guiding decisions about when to apply AL?

    What are other examples of possible criteria/principles?

  • Data and assessment 2 comments

    The following points were raised regarding data collection, evidence generation and assessment:

    • Data hierarchy: AL may require moving from RCTs as the primary/only determinant of market approval to some mix of RCTs, other trial designs (e.g., pragmatic trials), observational studies, registries, and community-based data.  What is the acceptable mix of studies & study design and level of evidence?  What are the limitations of the data?  Is there a need for novel methods?  Are different stakeholders more open/accustomed to different levels of evidence than others (e.g., HTA may be more familiar with observational data than industry)?
    • Patient groups: How to determine patient populations, e.g., on the basis of Phase 2 studies?
    • Outcomes: What outcomes (surrogate or otherwise) are important in AL, particularly where these are to be harmonized with HTA-specific outcomes?
    • Access to data/data sharing:  In AL/HTA harmonized approaches, who owns the data?  Who provides the data collection infrastructure?  Currently, regulators have all the data, HTA has only the data that companies provide.  What about intellectual property issues?
    • Problem of new drugs coming into the market that effect how older drugs are analyzed: confounding.

    ---> QUESTION:

    Are there other issues around data collection, evidence generation and/or assessment that should be considered?

  • Risk management

    The following topics regarding managing different kinds of risk related to AL approaches:

    • Uncertainty of benefits/harm: how to address clinical uncertainty/hazards to less "proven" technologies under AL?  Is it possible to share the risks (costs) of evidence development?
    • Clinical risk: how to address clinician's concerns about patient safety and possible harm, including risk of litigation, while patients are being treated with a technology subject to AL?
    • Cost/pricing risk:  Who pays for drugs under AL?  What evidence is this to be based on?  What is the relationship between initial and final price?  There may need to be a new approach to pricing in AL.  Commercial risk may not be viable.  What is the risk to public/health system budgets?

    ---> QUESTION:

    Are there other aspects of risk management that should be noted?

  • Innovation

    The following points were raised about the relationship between AL and technology innovation:

    •  Regulators already have restricted conditional approval approaches.  These approaches can "kill a product" because payers will not currently cover it with an AL designation.
    • Strict regulatory requirements effectively limit the extended use/repurposing of technologies.
    • AL/CED approaches may be perceived as a threat by industry as they "simply add requirements for more data without reviewing any requirements at the front end".
    • An integrated regulatory/payer approach would incentivize innovation.
    • Patent specificity

    ---> QUESTION
    Are there other aspects of the relationship between AL and innovation that should be noted?

  • Post-market

    The following points were raised by the Forum about post-market issues:

    • How to manage exit/disinvestment of unsuccessful technologies admitted under AL?  How to end AL agreement if criteria are not met?
    • What is the cost of enforcement/monitoring of technologies once approved for AL?
    • How to restrict use of a technology in practice ("spillover")?  There are no legal tools available for this.
    • AL may affect the bigger picture/pathway of how drugs are brought to market.


    Are there other aspects of the post-market phase of technologies that should be considered?

  • Decision making

    The following points were raised regarding decision making considerations around AL:

    • AL involves shifting a decision point of market access, but what is the appropriate point?  It is typically suggested to move this to Phase 2 or even Phase 1 of technology development.  What evidence is needed at different points?  What stakeholders need to be involved? When is the most appropriate point to consider pricing decisions?
    • What is the balance point between uncertainty of risk, uncertainty of benefit (regulator) and uncertainty of value (payer)?
    • Does AL automatically mean ME/CED is used as well?  If so, how might these be harmonized?
    • What if the regulator and payer disagree, e.g., does AL necessarily provide access to patients if the payers do not agree to cover the treatment even though regulators approve it?
    • With two (or more) decision points in AL, what if there is a discrepancy in the initial licensing decision and the final/full decision?


    What other issues are relevant to decision making in AL contexts?


  • Early dialogue

    The following points were raise regarding early dialogue:

    • There may be opportunities to link with early dialogue initiatives that give scientific advice in order to define data for (1) initial licensing/reimbursing, and (2) further steps for revision of licensing-reimbursing
    • Early consultations with stakeholders will enable prospective understanding/agreement regarding evidence expectations
    • EMA Safe Harbour enables a company to come to EMA without commitment (i.e., early non-binding agreement)

    ---> QUESTION:

    Are there other aspects or examples of early dialogue that should be considered in the Forum discussion?

  • Stakeholders 1 comment

    The following considerations were raised regarding stakeholders:

    • When is it appropriate to include specific stakeholders in defining & implementing AL?  For instance: payers,  HTA bodies, industry?
    • What kind of patient awareness is needed to provide informed consent to treatments under AL?


    Are there other issues around which stakeholders should be involved in AL process and when this should optimally occur?

  • Devices 1 comment

    The following points about devices were raised by the Forum:

    • How devices are affected/included in AL is unclear.  The context and issues are different for devices and diagnostics than for drugs.
    • Germany has a new law for adaptive licensing for devices to assess the potential for AL for medical devices.
    • USA has a parallel review program for devices; it is a type of adaptive licensing: FDA approval always includes limitations.
    • AL should be adapted for the specific technology in question (drugs, devices, biologics, etc.)

    ---> QUESTIONS:

    Are there other important issues to consider regarding devices, diagnostics or other non-drug technologies and AL?

    Are there other initiatives looking at how AL might be applied to non-drug technologies?

  • Legislative issues 1 comment

    The following legislative issues were mentioned:

    • How do different AL proposals fit within the current legislative framework? Are the proposals a legislative solution or a non-legislative solution (requiring policy changes, not legislative changes)
    • If clinical trials are done differently, AL could work under existing laws.

    ---> QUESTION:

    Are there other legislative issues to be considered in this topic area?