Two developments in 2004 further transformed the situation:
1. The introduction of a revised health technology assessment guideline by the National Institute for Clinical Excellence (NICE) in the UK; and
2. The introduction of revised technology assessment guidelines for new products and for the re-evaluation of products by WellPoint Pharmacy Management (WPM) in the USA.

Where the NICE and WPM guidelines represent a major change in requirements with the need:
(i) to accommodate adequately uncertainty in modelled cost-effectiveness claims and the requirement for a reference case (NICE); and
(ii) the requirement for naturalistic, active comparator trials together with ongoing monitoring and validation of claims for cost-effectiveness and systems impact (WPM).

Put together, the NICE and WPM guidelines present formidable challenges to manufacturers in both the UK market and in the US managed care sector. If other health technology assessment and reimbursement gatekeepers adopt these new evidentiary and analytical standards, then manufacturers will have to rethink seriously not only how they adapt their clinical development programs to accommodate the reference case and active comparator requirements in Phase III trials, but the ways in which they present cost-effectiveness and system impact claims to meet monitoring and validation standards.

Preparing health technology submissions for pharmaceutical products - Meeting Formulary Submission Requirements for New Product Assessments and Disease Area and Therapeutic Class Reviews, considers how manufacturers should respond to emerging evidentiary and analytical standards as exemplified by the NICE and WPM guidelines for formulary submissions.

The report considers, in particular, the implications of the standards required in the NICE and WPM guidelines for manufacturers preparing reimbursement submissions and it goes beyond being simply a review of evidentiary and analytical standards required by reimbursement and pricing authorities that have mandated a formulary submission dossier as part of the technology assessment of new products, to establishing the standards required of a global dossier. Meeting the NICE and WPM requirements ensures that specific or targeted dossiers can be assembled to satisfy the requirements of other jurisdictions. A global dossier, therefore, if structured to meet the standards of NICE and WPM, will also meet the requirements of other jurisdictions - where individual formulary submissions are customized to meet the needs of individual health systems.

"a poorly constructed and self-serving case, where the modelled case has clearly been driven by the need to justify cost-effectiveness, seldom stands up to a critical review."