Health technology assessment (HTA) was developed and adopted to better analyze the efficacy of health technologies and to inform decision makers often confronted with difficult choices regarding adoption and coverage. This iterative development has been described by Banta and Jonsson (Reference Banta and Jonsson1) and has become increasingly important to fiscally constrained health systems while not necessarily generating transparency, consistency, or alignment to policy (Reference Sorenson, Drummond and Kanavos2).
The scientific rigor of systematic review and health economic analysis is usually applied following regulatory approval (“postmarket”) and is based on premarket research or following data analysis from managed entry agreements (MEA). The increasing emphasis on MEAs is attributed to uncertainty, due to lack of information on effectiveness or costs (Reference Ferrario and Kanavos3). The aim is for payers and manufacturers to share the financial risk due to uncertainty and to expedite adoption. These agreements can take different forms, including price-volume agreements, outcome guarantees, coverage with evidence development (CED), and disease management programs. While MEAs may be used to offset cost pressures, when undertaken to address residual uncertainty regarding efficacy, such as coverage with evidence development, this suggests inadequate attention to coverage or health system needs and expectations in pivotal research focused on regulatory considerations. The complexity of regulatory and coverage decision making is compounded by variations in regulatory requirements internationally, the costs of undertaking premarket evaluations and a limited period of market exclusivity for nondrug technologies, driven by the relative ease of getting around existing patents. The latter reality may create pressure to realize developmental costs within a narrow time window and could be a cost-driver. Furthermore, coverage decisions following regulatory approvals have become increasingly complex so that premarket research to address regulatory requirements does not necessarily address coverage perspectives. This has resulted in a variety of approaches to more closely align protocol development between regulators and coverage decision makers which has met with variable success on a small scale or yet to be fully evaluated (4;5).
The schism between pre- and postmarket technology assessment of nondrug technologies has additional problems as identified in Ontario's approach to HTA over the past 10 years (Reference Levin, Goeree and Sikich6). This broad-based experience involving a scientific collaboration formed under the Ontario Health Technology Advisory Committee (OHTAC) included postmarket field evaluations of disruptive health technologies to resolve residual uncertainty following evidence review and produced an infrastructure to evaluate technologies in real time (Reference Levin, Goeree and Levine7). Ten of these field evaluations qualified as coverage with evidence development (Reference Levin, Goeree and Levine7). Certain realities became apparent in this process. First, the need for this approach confirmed that the quality or generalizability of premarket research for nondrug technologies was sufficiently lacking to cause uncertainty in decision making in over 20 percent of disruptive technologies considered relevant to health systems needs that warranted field evaluation. Second, 48 percent of 113 recommendations for individual technologies were negative, mostly due to low quality evidence. Third, the results of the field evaluation studies has given rise to concerns that the premarket clinical trials on which reimbursement decisions would have been made were not always consistent with the results from field evaluation studies. Examples, published elsewhere included drug-eluting stents (Reference Tu, Bowen and Chiu8), where restenosis rates for low risk patients were found to be similar irrespective of whether bare metal or drug eluting stents were used; positron emission tomography scanning (Reference Evans, Laupacis, Levine, Gulenchyn and Levin9) in which cancer-related indications were examined based on demonstrated clinical utility and have so far provided evidence for clinical utility only for lung cancer in multiple large studies; and computed tomography angiography (Reference Bowen, Chow and Freeman10) in which sensitivity compared with coronary angiography was lower than that reported in randomized controlled trials despite being tested in a teaching hospital environment. Fourth, in 10 years of postmarket HTA, no Canadian innovative technologies were submitted to OHTAC for evaluation. Because submissions to OHTAC for evidence synthesis and economic analysis on new nondrug technologies is initiated by health institutions or by the Ministry of Health and Long-Term Care (MOHLTC) to inform coverage decisions based on demand for adoption of new technologies, the absence of Canadian innovations raises concerns of obstacles between proof of concept and market adoption for young start-ups or companies finding access to other markets with less stringent regulatory conditions.
Uncertainty increases risk to innovators and investors, by leading to high rejection rates at the regulatory or coverage level which could stifle innovation by increasing risk to investors, delay adoption and reduce the period of market exclusivity. Furthermore, protracted and multiple studies to address shortfalls identified by regulators and payers results in increasing costs to manufacturers which are reflected in the final pricing and which could compromise access for patients.
THE CONCEPT OF A SINGLE HARMONIZED TECHNOLOGY EVALUATION PRE MARKET
An alternative model is needed to the existing increasingly convoluted, expensive, and protracted use of evidence for the purpose of regulatory control followed by further evidence analysis for the purpose of coverage decision making. Such an approach requires protocol development to be guided by the expectations of regulatory agencies and payers. In addition, the protocol should meet the needs and expectations of patients, the health system and end-users. This early HTA model should ideally harmonize premarket evaluation for regulatory purposes and existing postmarket requirements that form the basis for coverage decision making and adoption.
Despite the fact that innovation can improve patient outcomes and is a vital economic driver, divergent paths could develop between fiscally constrained health systems and new health technology development. When health systems are divorced from the drivers of innovation, the likelihood increases that new technologies are thrust on health systems without any understanding of their relevance or utility, which is elaborated on in the next paragraph. The lack of a process to screen out irrelevant innovations that have limited or no clinical utility will lead health systems to regard new health technologies as a liability rather than an asset. For nondrug technologies, this perception is compounded by the fact that nondrug technologies most often require front-ended one-time costs as opposed to drugs where costs more often compound over time but can be amortized over the length of the illness especially in chronic disease management.
Merging the interests of health systems and innovators has never been so important and this can best be achieved through closer partnerships between innovators and health systems in the premarket space. Closer agreement is required further upstream in the technology lifecycle between new technology pipeline development and the needs of health systems. This would include criteria for determining relevance such as the definition used by the premarket MaRS EXCITE program which defines relevance by disruptiveness, optimizing patient outcomes and/or health system efficiencies and other issues of relevance to health systems such as convergence with overall strategic direction and policies. New health technologies that meet these criteria should be evaluated in the premarket space because they are of interest to patients, health systems, and to industry. The key to this process is the willingness for industry, government, regulators, payers, patients, and end-users to become involved in protocol design so that the protocol reflects these balanced interests, are incorporated in study design and reflected in primary and secondary outcomes. While this process can never guarantee a favorable regulatory or coverage decision, it will mitigate the risk of rejection.
The evaluation of new technologies should be funded by industry, as is currently the case for premarket evaluations but ideally, the clinical trial design, protocol development and data acquisition and analysis should be undertaken by neutral clinical trials methodology centers at arms’ length from industry. It is also desirable for systematic review and economic analysis to be conducted premarket and in parallel with the clinical evaluation as a way of evaluating the relative efficacy and economic reality of the new technology once the data from the clinical evaluation are available.
Engagement with decision makers before finalizing clinical trial protocols can improve successful final coverage decisions and expedite adoption (Reference Hofer, Jakobsson and Zafiropoulos11) There are increasing examples in which this advice is offered to manufacturers early in the technology lifecycle, some of which are referenced here (5, Reference Hofer, Jakobsson and Zafiropoulos11).
There are two additional considerations that pertain to collaborative premarket evaluation. First, it should be possible to define conditions of adoption of new effective technologies into the health system. This is of benefit to the health system because it provides sufficient lead time to prepare for the adoption of nondrug technologies which have an impact on end-user training, reimbursement, health human resource requirements, institutional infrastructure and services and to realize opportunities to modify access to pre-existing less effective alternatives. Second, given that a harmonized single premarket study will expedite adoption, there should be opportunities to continue to track more invasive technologies for longer-term safety and effectiveness postmarket.
DEVELOPING PROOF OF CONCEPT
The approach described above was implemented in Ontario, Canada, in February 2012 and is being reported elsewhere. This program, called Excellence in Clinical Innovation and Technology Evaluation is run out of the MaRS Development District in Toronto (MaRS EXCITE). To date, fifty companies have applied to have their technologies evaluated, nine technology evaluations have been activated, and six are undergoing further review having been approved by the Board through the most recent call for innovation. The first technology will be fully evaluated by December 2015 is a disposable mask that is worn during sleep at home, avoiding the need for sleep laboratory testing for the diagnosis of uncomplicated sleep apnea. Plans are underway to develop conditions of adoption for this technology by the health system.
While there are increasing examples of engagement by HTA organizations, payers, and regulators with industry in the premarket space, some of which are referred to above (5, Reference Hofer, Jakobsson and Zafiropoulos11), the MaRS EXCITE program is the first of its kind to develop a fully comprehensive approach to evaluation that includes a collaborative approach to clinical trial protocol development that includes all parties likely to be involved in regulatory, coverage, and adoption considerations. Within this program, clinical trials are conducted through methodology centers linked to one or more of twenty four research hospitals and systematic review, economic analysis and defining conditions of adoption into the health system are included as part of the process.
CONCLUSION
Health technology assessment was originally applied, in part, to new health technologies as a decision tool once the technology had satisfied regulatory approval. This is not the most appropriate place in the technology lifecycle for this evaluation to occur. A more constructive and meaningful approach would be through single studies that harmonize regulatory and coverage considerations and that include perspectives of potential stakeholders that could be impacted by the technology. This would have the desired effect of encouraging the expedited adoption of disruptive effective technologies through this less convoluted and more efficient approach. It could also reduce costs to industry, reflected in more affordable technologies, drive economic development and innovation and, above all, improve patient outcomes and/or health system efficiencies.
CONFLICTS OF INTEREST
LL receives funding from MaRS through an Ontario Government grant
