Implementing Coverage With Evidence Development

HTA QUARTERLY | SPRING 2018

Market Trends and Updates: Is There Consensus on Implementing Coverage With Evidence Development?

Managed entry agreements (MEAs)—contractual agreements that allow market access for drugs by distributing the risk of uncertainty between the budget holder and the pharmaceutical, device, or diagnostics manufacturer—are used in many countries to control financial risk. MEAs are broadly divided into financial-based agreements and performance-based agreements. Currently, the former is more common due to its simplicity and familiarity, but the latter is becoming increasingly prevalent due to the drive for reimbursement agencies or budget holders to concurrently manage costs when making timely and appropriate coverage decisions.

Coverage with evidence development (CED) refers to one type of performance-based risk-sharing arrangement that is often used to manage outcome uncertainty (Figure 1, shown as “coverage dependent upon evidence generation”). It links population-level reimbursement to coverage based on continued prospective data collection that will address key element(s) of uncertainty existing at the time of regulatory approval. Frequently, this uncertainty involves information related to an intervention’s effectiveness that may impact healthcare resource use or outcomes.

Figure 1.

CED Definition

The decision to provide coverage can be associated with research to be conducted alongside product use (OWR) or only when the product is used in the context of research (OIR). Following the data collection period, there may be a pre-agreed adjustment or renegotiation to modify price or coverage.

OWR vs. OIR

When to Consider CED?

CED agreements are best suited in situations where a treatment or technology demonstrates promise for significant benefits, yet uncertainties remain regarding its future clinical or economic impact at the time of approval (Figure 2).

Figure 2.

For budget holders, CED offers an option to make a technology available in a controlled manner while allowing them to predetermine which evidence will be needed to ensure coverage of the technology. Budget holders can gain greater certainty and greater value for the money spent when employing a CED.

For manufacturers, CED provides the opportunity to introduce a new and promising technology which otherwise might be rejected or delayed. Through CED arrangements, manufacturers can hasten the availability of promising therapies to address unmet patient needs. Given that the funding for additional evidence generation associated with CED may be covered in full or in part by public sources, rather than by the manufacturer, these arrangements may also provide a means for data collection at a reduced cost.

For both patients and clinicians, CED results in earlier access to new and promising diagnostic tests and medicines, leading to an increase in available treatment options.

Implementation and Challenges

While potentially beneficial across stakeholders, CED arrangements can also pose substantial challenges (Figure 3).

Figure 3.

For a CED agreement to be successful, the evidence gap and resulting uncertainty must be overcome through prospective gathering of additional evidence, generated within an appropriate time frame, and addressing the element(s) of uncertainty for recommending coverage. It is also beneficial to have a clearly laid out and formalized process with all stakeholders regarding how and when future decisions will be tied to the additional evidence that is generated. CED can employ observational studies and RCTs in either an OWR setting or an OIR setting, as applicable and appropriate.

Global Perspective: Updates and Disparities in CED Agreements

A number of countries are using or have used CED in their reimbursement approval processes. The United States and the United Kingdom both updated their CED programs in the last 5 years (2016 and 2013, respectively), and the Netherlands introduced a new approach to CED agreements in 2012. Other countries using CEDs include Sweden, Australia, Italy, Belgium, China, and France. While use of CED agreements is widespread, the approach to their implementation is not consistent across countries. In many instances, country-specific information on the process for establishing a CED is limited, which can pose difficulties for manufacturers.

United Kingdom

Launched in mid-2016, an updated appraisal process for drugs reviewed through the Cancer Drugs Fund (CDF) aims to allow patients access to promising new cancer treatments while more evidence is gathered on effectiveness.
By November 2017, NICE had recommended 11 treatments for use within the CDF.
If a drug has the potential to meet the criteria for regular approval but significant uncertainty remains, the drug can be made available within the CDF while additional evidence is generated to resolve the key areas of clinical uncertainty and show that the medicine works in the NHS population.
The process begins with a drug not recommended for routine use and proceeds by evaluating the therapeutic necessity for the drug and feasibility of evidence generation. Once recommended, specific criteria and requirements for prospective evidence generation are collaboratively established.

United States

The majority of CED arrangements in the US are administered through the Centers for Medicare & Medicaid Services (CMS) as part of the national coverage determination (NCD) and involve medical devices or diagnostics. In 2017, there were an estimated 22 CED agreements published by CMS, with a preponderance in cardiology followed by oncology.
New guidance for the CED program established by CMS was issued in 2013 in response to several implementation challenges. Under this program, a technology may be approved for a patient on the condition that they are participating in a registry or clinical trial (OIR) and the routine costs of an approved clinical trial in both treatment arms are paid. At the end of a cycle, CMS reconsiders the CED coverage decision and may remove the requirement for study participation as a condition of coverage.

Sweden

From 2008 to 2016, there were a total of 65 agreements in Sweden with a CED component spanning a number of different disease areas including oncology and endocrinology.
Requests for CED agreements by TLV are driven by weak cost-effectiveness models, especially if there is uncertainty around utility, patient benefits, transition probabilities, and model structure. Additional drivers include low relevance of evidence for clinical practice, extrapolation of long-term efficacy, and lack of comparative effectiveness data.
Agreements are typically set at an average length of 3 years; however, review of past CEDs suggests that, for a significant number

The Netherlands

In 2012, an updated CED policy was put in place to cover interventions that are not yet part of the basic reimbursement package due to lack of evidence on effectiveness.
Criteria for technologies to be considered in the CED system are the definition of the essential evidence gap, the specific research question and quality of a detailed research protocol, the feasibility to collect relevant evidence during the 4-year period, and the value relative to the research budget needed.
A limited number of technologies can be temporarily included in the national reimbursement package for a 4-year period.

Conclusions

Implementation of CED agreements provides earlier access to therapies and technologies for which some aspects of the evidence are still uncertain at the time that efficacy and safety are established. Challenges do remain in funding sources, operational issues with respect to data collection, and managing competing interests of the various stakeholders. However, when these challenges can be overcome, CED agreements help distribute and mitigate risk and enhance the available evidence base for further coverage decisions. Moreover, they may allow manufacturers to introduce drugs that might otherwise be rejected or delayed, and offer patients earlier access to often much-needed innovative treatments.

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