An increasing number of decision makers now require health economic support for reimbursing and listing new products, specifically in relation to their impact at the local level. With the majority of regulatory submissions still based on core global data, there is a pressing need for best practice guidance on customising key results for individual markets.

The priority, according to experts at a recent IMS Health symposium, is early, forward planning and flexible, transparent modelling that is responsive to local requirements for reimbursement. The symposium formed part of the International Society for Pharmacoeconomics and Outcomes Research’s (ISPOR) 8th Annual European Congress held in Florence in November, and focused specifically on issues around the transfer of economic evaluations and potential solutions for generating estimates that are applicable to local situations. Led by Prof. Lieven Annemans, Principal, HEOR at IMS, and former president of ISPOR, the meeting attracted more than 400 delegates keen to gain insights from industry expert, Dr Jens Grueger, Head of Pricing and Health Economics at Novartis, and health economics specialist Dr Frank-Ulrich Fricke, Principal, HEOR at IMS in Germany.

Requests converging but localisation key

Dr Grueger began the session by outlining some of the key issues facing pharmaceutical companies as they strive to meet the growing demand for more extensive and sophisticated economic analyses. On the positive side, he noted a convergence in the nature of data requests from decision makers, which typically now fall under four main headings:

1. Current treatment standard and justification of unmet need

2. Clinical data relative to current treatment standard in the respective country

3. Evidence of cost effectiveness

4. Budgetary impact in the local setting

But despite the emerging consistency, customisation of results to the local setting is important. “As manufacturers we are never in a position to provide country-specific data for all the countries that are now requesting this information”, explained Dr Grueger, “We have a set of core clinical trials and if we are lucky there are at least two countries where we will have specific local data for a sufficient number of patients – typically the US and Japan. For the rest of the world, and that includes Europe, this is less likely”. Moreover, as he went on to clarify, the expectations of different constituencies remain very diverse, complicating the development of appropriate models - now a “non-negotiable” fact of life for reflecting the results of clinical trials in alternative populations.

The complex nature of the modelling process is perhaps not surprising. Extrapolating a core set of clinical data to different settings of care involves a detailed process of identifying multiple variables, gathering extensive data and designing and populating the model itself. Factors such as epidemiology, treatment alternatives/comparators, outcomes, management of key events, resource use, duration, and so on, must all be taken into account along with relevant discount rates, financial perspectives, resource costs, etc. Models must therefore be sufficiently flexible to accommodate a range of diverse parameters including different patient segments, treatments, resource categories, and outcomes. As Dr Grueger pointed out, “The credibility of the information we produce for each country depends greatly on the transparency of the model we provide”.

Lost in translation

Dealing with the outputs of country-specific economic evaluations is also a challenge since the results can vary significantly from those observed in the clinical trial. Wide differentials in treatment outcomes, relative performance, and the magnitude of benefits and cost-offsets are not unusual. Interventions shown to save money in one country can represent huge added costs in another. The use of methotrexate compared with laparoscopic salpingectomy in the management of ectopic pregnancies is a documented case in point: its impact has been found to range from a cost saving of nearly $800 per patient in one market to an added cost of nearly twice that amount in another. Variations in reimbursement requirements, diagnosis and treatment, resource use, and valuation of resources and outcomes all contribute to these discrepancies. As Dr Grueger noted, “Consistency then becomes very difficult and long explanations are often required as to why the observations are so different”.

Towards solutions

Strategies for handling these country differences depend greatly on the intended purpose of the analysis, a point underscored by Dr Fricke in his discussion of potential solutions. If the intention is to extrapolate clinical trial data to a particular country or region then customisation to local requirements and target audiences will be essential. In these cases, advance discussions with decision makers can be helpful to clarify their needs and ensure that the model proposed will be acceptable. If, on the other hand, comparing outcomes across multiple countries is the primary goal, then achieving standardisation will be key to meeting international objectives and a broader target audience. Here the challenge is to identify a set of common resources that can form a basis for comparison across different settings.

Strategies will also vary according to the type of study being conducted. Dr Fricke considered the potential options for three - modelling, piggy-back assessments and real-life evaluations.

A modelling approach

First and foremost, models should aim to be transparent, flexible, populated with a complete and consistent set of data and be entirely relevant to the perspective of their intended audience. Among other factors, inputs need to include:

• Epidemiological data on pathways of care, patient segments and treatment patterns
• Information on treatment for specific events and in relevant patient populations
• Local resource use and cost data

The type of information required on resource use will depend on specific criteria around the event costs being addressed, the perspective of the analysis (e.g. providers, payers, patients) and the funding/reimbursement systems involved (e.g. lump sum, fees for service, etc.).

The definition of the “relevant patient population” in a country will be a function of product registration and positioning but, as noted by Dr Fricke, it is important to be aware that local opinion leaders will often have their own, very different, thoughts on positioning the intervention. This is only one of many important reasons to begin the modelling process as early as possible (alongside Phase I/II). Such a strategy can be critical to establishing clear positioning from the start and disseminating a consistent message at the local level well in advance.

Piggy-back studies and real-life evaluations

Additional approaches to generating health economics data that were also briefly discussed include “piggy-backing” on an existing clinical trial and carrying out real life studies to capture occurrences after an event in the clinical trial. Piggy-back studies have the ability to generate quality data for a lower cost than a dedicated prospective health outcomes evaluation, but strategies are dependent on the clinical basis of the trial and the efforts required to incorporate local specifics. It is important to take different pathways of care and financing systems into account and here local expert panels and guidelines can be helpful. Real-life studies are at risk of heterogeneity and also rely heavily on local validation.

Keys to credibility and reimbursement success

Delegates were left with a number of important, take home messages to ensure the credibility of health economic evaluations and successful reimbursement and listing:

• Start early and involve key countries from the outset
• Make sure that your health economic model is:
• Flexible and transparent
• Responsive to local reimbursement requirements
• Transferable across different countries
• Populated with transparent costs
• Supported by multiple sensitivity analyses
• Appoint someone with the authority and credibility to front the model with decision makers at all

ISPOR accolade for IMS HEOR contributed presentations

The symposium underpinned an extensive programme of IMS activities at the congress. These included more than 50 poster and oral presentations of new health economic findings in a range of countries and therapeutic areas and a hands-on workshop comparing the role of health technology assessment and economic analyses in various European healthcare systems.

Two IMS contributed presentations received the coveted accolade of an ISPOR Contributed Research Award; a pharmacoeconomic evaluation of aggressive cholesterol lowering after acute coronary syndrome in Belgium was selected as Best New Investigator Poster Presentation, and a UK cost-utility analysis of self monitoring of blood glucose in patients with Type II diabetes received the prize for Best Podium Presentation.

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