OBJECTIVES Payers have a perception that orphan products are extremely expensive. The current health technology assessment (HTA) systems might be too restrictive for orphan drugs, therefore potentially denying patients access to life-saving medicines. While price is important, it should be considered in relation to a broader range of product attributes, such as unmet need and disease severity that are not considered in cost-effectiveness analysis used by many HTA agencies. To overcome these challenges multi-criteria decision analysis (MCDA) has been proposed as an alternative to evaluate technologies.  The aim of this study was to identify criteria reported in the literature, and to assess their impact on the total “score” for each product in relation to price. METHODS A systematic literature review was conducted to identify the most frequently cited attributes in MCDA.  From the leading attributes identified, we reviewed and plotted the relationship between single attributes and the average annual treatment costs for several drugs used in the treatment of endocrine-related rare diseases. Annual treatment cost was based on UK prices for the average daily dose per patient.  RESULTS The three most frequently mentioned attributes were ‘disease severity’, ‘treatment impact on condition’, and ‘level of research undertaken to support use of the product’. Disease severity was not shown to influence product price. Similarly, orphan drugs are not necessarily more expensive than products without orphan drug status. There is little discernible relationship between treatment ‘convenience’ and average annual treatment cost.  A trend was observed between the market size and the average annual treatment cost.  CONCLUSIONS If society is concerned about equity and equal access to medicines for all patients, MCDA may offer a viable alternative to inform in reimbursement decisions for orphan drugs. The analysis can be used to inform investigations on the application of MCDAs in rare diseases.