It is common practice for developers of new health care technologies to engage in early dialogue with the major regulatory agencies; such discussions frequently center around the proposed clinical trial designs to support the registration of new interventions and suggestions on their improvement. Pricing and reimbursement agencies are increasingly using the results from health technology assessments to inform their decision making for new technologies. Such assessments are invariably underpinned by the phase 3 clinical trial evidence which may not provide answers to the key questions. Technology developers are beginning to realize that direct, early dialogue on the evidence requirements of the major pricing and reimbursement agencies, before phase 3 clinical trial designs for their key development compounds have been finalized, may be beneficial. This article reports on the pioneering efforts of one technology developer in seeking early dialogue with seven pricing and reimbursement agencies in five countries globally in 2007–2008 on their likely evidence requirements for a new oral treatment for patients with chronic plaque psoriasis. The pilot project demonstrated that a feasible process of early dialogue could be established, through a face-to-face meeting with prior circulation of a briefing book. Although there was some variation in the advice the similarities far outweighed the differences. More experience of early dialogue needs to be accumulated, involving a wider range of pricing and reimbursement agencies and compounds. The conclusion of this study, however, was that early dialogue can be a worthwhile process for all parties and can lead to a common understanding about evidence development for market access.
It has been common practice for several years for the developers of new health care technologies (primarily new pharmaceuticals) to engage in early dialogue with regulators, such as the US Food and Drug Administration. The reasons for this are self-evident. Given the large and costly investment in clinical research and development to establish the efficacy and safety of a new product, it is important for the company to be reasonably certain that, if research of an adequate quality is conducted, approval to market will be granted if the net clinical benefit is considered to be positive. Therefore, technology developers often present their proposed clinical trial designs to regulators in order to obtain feedback and to receive suggestions on their improvement.
A more recent development is that in several jurisdictions a health technology assessment, including an economic evaluation, is now required as part of the processes for determining the price and reimbursement status for new technologies. In these jurisdictions the process is that the sponsor of a new technology prepares a submission containing such an evaluation, according to an agreed set of guidelines [1]. Although the published guidelines give some clues as to the scientific quality of clinical and economic evidence that may be required, they do not provide sufficient detail to answer important strategic questions such as “to obtain reimbursement for first line use in a given category of patients, precisely what evidence should be submitted?” This is understandable, given they are not written for this purpose; they are written to help potential applicants prepare a submission from the evidence that has already been generated rather than specifying, before the event, what evidence should be generated.
Although the requirements for the submission of evidence to pricing and reimbursement agencies do not have the same legal status as submissions to regulators, from the manufacturer's perspective they are gaining increasing importance, because they are critical for market access for a new product. Market access, not product licensing, is the ultimate goal, and technology developers are increasingly viewing the clinical development program as providing data for both purposes.
A potential complication is that the evidence required for a pricing and reimbursement submission might involve the production of clinical data that go beyond that required for a regulatory submission. For example, in order to obtain reimbursement for first line therapy, it may well be necessary to demonstrate the product is more efficacious than an existing first line therapy, or it may be necessary to collect data on an outcome that is of interest to a pricing and reimbursement agency, although not required by a regulator. For example, some new anticancer drugs have obtained regulatory approval (in some jurisdictions) based on demonstration of improvements in progression-free survival, whereas some pricing and reimbursement agencies would likely require evidence on overall survival, unless they can be convinced that the relationship between the two outcomes has been well established [2], [3] and [4].
Therefore, a growing number of technology developers have realized that a dialogue on evidence requirements may be beneficial with pricing and reimbursement agencies before phase 3 trial designs are finalized with regulators [5]. This article reports on the pioneering efforts of one technology developer in seeking early dialogue with several pricing and reimbursement agencies. It reflects on the main lessons learned and considers future directions and challenges.
This pilot project demonstrated that a feasible process of early dialogue could be established. Although there was some variation in the advice obtained from the various agencies, the similarities far outweighed the differences. Several important conclusions were reached about the viability of the company's aspirations for product positioning, the desirability of particular comparisons, the outcomes to be used in trials and the length of trial follow-up.
More experience of early dialogue needs to be accumulated, involving a wider range of agencies and compounds in different clinical areas. If the process can be shown to be beneficial from a societal perspective, it would be desirable for adequate funding to be made available, either by expanding the budgets of the relevant agencies, or through self-financing arrangements like those recently established by one of the agencies.
