How Should Functionally Equivalent Drugs be Reimbursed?

Statutory reimbursement agencies as well as private insurers throughout member states of the Organization for Economic Cooperation and Development (OECD) reimburse the cost of medicines on the basis of criteria that include robust clinical evidence, budget impact analysis, and incremental cost effectiveness. The Centers for Medicare and Medicaid Services (CMS) in the US are no exception to this rule and are, in principle, seeking to maximize benefit for their Medicare enrollees, whilst ensuring reasonable drug outlays for the small number of drugs that they reimburse. This paper provides a retrospective analysis of the way two functionally equivalent drugs are treated for reimbursement purposes by the CMS; the period under consideration was 2001–3. The two drugs, epoetin-α and darbepoetin-α, are used for the treatment of anemia in renal failure and in patients receiving chemotherapy. By reviewing the publicly available pharmacological and clinical data of epoetin-α and darbepoetin-α, the paper confirms the two drugs’ functional equivalence, despite their structural differences. The implications of dose conversion ratios and costs to Medicare are subsequently explored. It is argued that the issue of dose equivalence between epoetin-α and darbepoetin-α has significant implications for patients, practitioners, and payors. A payor’s perspective is adopted in this respect, whereby clinical evidence and pricing data are used simultaneously. Based on the clinical evidence, a dose conversion ratio for epoetin-α:darbepoetin-α is established, which achieves a comparable clinical effect for the two drugs and this is set to be <254IU:1μg. The incremental costs to Medicare are calculated subsequently. The Average Wholesale Price and the Outpatient Prospective Payment System rule that Medicare uses to reimburse providers are used and suggest that treatment of cancer patients with chemotherapy-related anemia with epoetin-α would save Medicare an estimated $US600 million each year. Patients would also benefit significantly in terms of lower co-payments for epoetin-α. The evidence is supportive of the decision made by the CMS to reimburse the two drugs at the rate reflecting the achievement of comparable clinical effects and therefore reducing the pass-through payments for darbepoetin-α to zero for the 2002–3 fiscal year.     

Increased lymphocyte beta-adrenergic receptor density in progressive multiple sclerosis is specific for the CD8+, CD28- suppressor cell.

Beta-adrenergic receptor density on T cells from healthy humans is greatest on suppressor cells (CD8+, CD28-) and the effect of catecholamines, secreted by the sympathetic nervous system, predominates on this subset. The sympathetic skin response, a measure of sympathetic nervous system function, is absent in most patients with chronic progressive multiple sclerosis (MS). We measured beta-adrenergic receptor density on suppressor cells, cytotoxic cells, and monocytes from patients with chronic progressive MS and healthy control subjects. Control receptor density on suppressor cells was 2.8 +/- 0.3 fmol/10(6) cells versus a density of 5.1 +/- 0.7 fmol/10(6) cells for patients. Cytotoxic cell (CD8+, CD28+) receptor density was 1.4 +/- 0.4 fmol/10(6) cells in control subjects and 0.9 +/- 0.3 fmol/10(6) cells in the patients. Monocytes displayed beta-adrenergic receptor densities of 2.6 +/- 0.4 fmol/10(6) cells in normal individuals and 2.7 +/- 0.4 fmol/10(6) cells in the patient group. CD8 lymphocyte beta-adrenergic receptor densities in patients with relapsing-remitting and those with stable MS were not different from control values, yet were significantly less than the values for patients with chronic progressive MS. We find that mononuclear cells from healthy control subjects and patients with chronic progressive MS proliferate in response to 200 units/ml of recombinant human interleukin-2 (IL-2) similarly. However, IL-2 treatment increased beta-adrenergic receptor density on normal mononuclear cells, but failed to increase it on mononuclear cells from patients with chronic progressive MS.(ABSTRACT TRUNCATED AT 250 WORDS)     

Are ADDH and ADHD the same or different?

To assess the relationship between the DSM-III criteria for attention deficit disorder with hyperactivity (ADDH) and the DSM-III-R criteria for attention-deficit hyperactivity disorder (ADHD), children from an inner city parochial school were evaluated using a 30-item teacher questionnaire consisting of the DMS-III and DSM-III-R criteria for these disorders, the revised Conners Parent and Teacher Questionnaires, and a continuous performance test. Diagnostic groups were established based on teacher ratings of the DSM items and evaluated in relation to the rating scale data and continuous performance test. While children who were identified by teachers as having ADDH almost always satisfied the criteria for ADHD, a new group of children who were hyperactive and impulsive but less clearly inattentive also met the criteria for ADHD. Implications of the change in diagnostic criteria are discussed.