Molecular Testing for Response to Treatment for Chronic Myeloid Leukemia (CML) Patients: Information Available to Decision Makers on the Costs and Analytical and Clinical Validity of Alternative Approaches.

Several “home-brew” and commercially available BCR-ABL gene transcript molecular monitoring detection methodologies are in use for the detection of residual leukemia disease in patients with CML. However there are a large number of variables between sample collection and final result including different volumes and cell counts samples, different RNA extraction methods, different detection instrument platforms, different reference genes to compare BCR-ABL ratios to an internal control gene and different comparators for quantification. Overcoming this lack of comparability can be attempted by either a standardization of procedures or external calibration of results obtained with the different approaches. However even with standardization or external calibration it is difficult to compare results obtained from different laboratories because of the wide range of techniques used. Equally importantly, information is required for decision makers not only on the analytical and clinical validity of the tests but also on their overall cost and cost effectiveness. The objective of this study was to assess the quantity and quality of information available to decision makers to choose the most appropriate testing procedure.

English language systematic literature review on the i) costs ii) cost effectiveness and iii) analytical and clinical validity (including intra- and inter-laboratory variability) of BCR-ABL molecular monitoring testing in CML.

From approximately 100 papers retrieved for detailed analysis we found no published studies which examined the costs or cost effectiveness of molecular testing in CML. We found one (now dated) health service technology assessment report which examined the cost effectiveness of polymerase chain reaction in the diagnosis and monitoring of patients with BCR-ABL gene rearrangement in CML. There are a number of studies which have compared alternative approaches using the same patient sample in molecular monitoring in the same laboratory. However, unambiguous conclusions from these studies are difficult to make due to i) the use of different comparators and or testing platforms, ii) studies being conducted in different time periods with consequent changes in technology and iii) wildly varying sample sizes which make comparisons of statistical significance difficult. There are several well conducted studies which have examined the variability of results from different laboratories in controlled environments.

Decision makers require information on both the costs and benefits of competing approaches to molecular monitoring detection methodologies to make informed choices on the most appropriate form of patient management. Although there is a degree of evidence on the analytical validity for different approaches to CML molecular testing, information on the costs and cost effectiveness of molecular diagnostics in CML appear is essentially non-existent. Although it is known that testing variability has potentially serious implications for patient outcomes it is also the case that decision makers require information on the costs and cost-effectiveness of different approaches to CML testing to maximize the return on health budgets that are experiencing on-going financial pressures.

Braendle:Novartis Pharmaceuticals: Employment. Hudson:phmrconsulting: Consultancy. Diego:Novartis Pharmaceuticals: Employment. Mark:phmrconsulting: Consultancy.