Original article
Evidence Requirements for Innovative Imaging Devices: From Concept to Adoption

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Changes in the regulatory and reimbursement environment for advances in imaging in the United States are leading to increasing requirements for formal clinical evidence of efficacy, effectiveness, and safety. The authors describe 5 phases of an imaging product's lifecycle: design, regulatory clearance and approval, early adoption, reimbursement, and full adoption. Each phase has distinct needs for clinical evidence. With increasing costs of clinical evidence generation, the question of ownership of the responsibility to gather clinical evidence at each successive phase becomes important. Mismatch between the pace of advances in imaging technologies and the time required to do formal clinical trials to clear regulatory and reimbursement evidence requirements threatens patient access to the benefits of innovation such as reduction in exposure to radiation. Public and payer requirements for clinical evidence must also be evaluated for their impact on incremental design improvements, which have historically characterized advances in diagnostic imaging.

Introduction

The first generations of plain film x-ray, CT, ultrasound, and MRI were so transformative that questions of efficacy and effectiveness were usually nonexistent. Today, with the rise in health care expenditures and advances in computer science fueling growth in technologies throughout the life sciences, innovations in imaging, especially major advances, are coming under increased public policy analysis. Manufacturers deciding to introduce new imaging technologies into the US market must plan for an increasing set of regulatory, reimbursement, and adoption hurdles.

Specifically, federal regulators and payers (and their private counterparts) regularly invoke more highly defined requirements for evidence of efficacy and effectiveness, and safety and necessity. We characterize the types of clinical evidence corresponding to the 5 phases in a successful product lifecycle from clinical introduction to full adoption and the appropriate means of generating and using such evidence. We describe (1) product design, (2) FDA clearance and approval, (3) early clinical adoption, (4) reimbursement, and (5) full clinical adoption.

This sequence of evidence phases for new applications of novel features in medical devices is driven by the unique US regulatory and reimbursement environment. Although the development of imaging technology is global, the United States has been the largest and most influential adopter of advanced imaging. Therefore, increases in US evidentiary standards may have a global impact on innovation and access to imaging.

In general, private markets, whether for health care or other goods, ensure economically valuable and efficient transactions through price signaling as consumers match their personal marginal utility to market prices while at the same time producers are matching their marginal costs to those same prices. In the US health care system, most coverage and payments are effectively set by CMS, heavily influencing private payers. Historically, CMS paid for services that were “medically necessary,” so the discussion of value was not part of this conversation, but new measures of utility or value are increasingly being demanded [1].

Assessment of clinical utility will differ according to the varying perspectives of payers, providers, employers, patients, and politicians. Utility from the vantage point of payers and providers may be driven by cost, each driven by a profit motive, while from the vantage point of employers, the time to return to work would also be considered. Conversely, patients may be less concerned with cost (if they are not paying) but more concerned about quality and quantity of life; for them, the relevant outcome of a diagnostic procedure is change in diagnosis or treatment. That is to say, diagnostics are different from therapeutics; as distinct from the outcome of a therapeutic intervention, a diagnostic outcome is a change in treatment plan. This is clear from the fact that a diagnostic test may result in changing plans for concerted therapeutic intervention to watchful waiting or palliative care.

Politicians may be concerned with access across the entire population. These viewpoints can lead to divergent assessments. For example, if a category of expensive imaging procedures enabled a choice of therapy to prevent sudden death, a patient's perspective might suggest that this is extremely valuable, whereas a payer's perspective might suggest the opposite because the procedure may now generate an entirely new set of care expenditures in exchange for a relatively small overall improvement in survival. An employer or societal perspective might be influenced by whether the patients are of working age [2]. Changes in the current evidentiary standards are being driven by payers' perspective, so we will focus on that reasoning.

In this paper, we outline the sequential generation of clinical evidence for new imaging technologies. We do so from the point of view of a manufacturer deciding whether to make an investment in research and development of innovative features or applications in imaging.

We outline 5 phases of evidence development for imaging applications and technologies (Table 1). Each of the 5 phases of evidentiary development leads to a decision point for investors in and manufacturers of imaging technologies as they weigh opportunity costs. The monetization of investment costs and returns stretches over many years, and therefore investment decisions will be discounted over time using net present value calculations.

Section snippets

Phase 1: Product Design and Introduction

Unmet clinical imaging needs can be addressed by new devices or novel features in current devices. Whether as additions to existing products or as elements of a completely new product, these features are captured in a design history file with a view to describing the product for which marketing authorization is requested. Clinical evidence gathered during this phase is useful in refining the design, gaining commitment to further investment in development of the product, and confirming the

Phase 2: Regulatory Clearance and Approval

Once a company decides to move forward with market introduction (on the basis of business planning, clinical and bench data, etc), the regulatory strategy and evidence needs are mapped out. The FDA classifies medical devices into 3 groups: classes I, II, and III.

Class I devices are considered low risk and primarily exempt from the 510(k) premarket notification clearance route. The 510(k) route (21CFR807.81) is the submission process to the FDA to demonstrate that the medical device is at least

Phase 3: Early Adoption

Once the FDA has cleared or approved a product for marketing, the device will likely become available for physicians to use. To the extent that the device is innovative, new clinical questions can be answered. For example, when spiral CT scanners became available, radiologists could look for appendicitis; as faster CT scanners and power injectors became available, chest CT could be used to look for pulmonary emboli; and more recently, as 64-slice CT became available, coronary arteries could be

Phase 4: Reimbursement

Historically, reimbursement for new health care technologies was directly tied to physician adoption. If the technology was “medically necessary,” as loosely defined under the original Medicare enabling statute, it would be covered [1]. From a manufacturer or investor perspective, this reimbursement policy meant that simple product utility to clinicians in clinical decision making was the prime determinant of business success or failure.

Congressional concern with spending growth has led to

Phase 5: Full Adoption

Widespread adoption of the technology or device is the final hurdle for manufacturers of imaging equipment. Manufacturers and investors perform significant “due diligence” in coming to their prediction of the level of adoption of their products by clinicians. Historically, the evidence the manufacturers used was grounded in market research and expert opinion rather than clinical evidence. Even without any formal clinical trials, the discipline of the marketplace exerted very strong pressure on

Conclusions

Many factors influence medical imaging technology adoption with various stakeholders, but the ultimate basis of acceptance and use is strong clinical evidence supporting the diagnostic value.

Advances in computer science are driving rapid growth in the capabilities of imaging devices, increasing the adoption of these devices and thus the substitution of precision diagnosis for empiric clinical evaluation. The resulting growth in the proportion of health care dollars spent on imaging has occurred

Cost Benefit Analysis

Compares potential monetary costs with benefits of initiative.

Cost-Effectiveness

Measures monetary costs relative to a measure of effectiveness (incremental cost per units of blood pressure or cholesterol reduced). Since costs and benefits are measured in noncomparable units, their ratio provides a yardstick with which to assess relative (productive) efficiency. Incremental cost-effectiveness ratio’s (ICER) allow CE comparison between technologies.

Cost Utility

Is an adaptation of cost-effectiveness analysis that measures an

Acknowledgment

We gratefully acknowledge work by Eric Z. Silfen, MD, chief medical officer of Philips Healthcare, in the strategic direction of this paper.

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