856 DRUG COSTS on
PATHOPHYSIOLOGY OF DIABETES
SIR,-In his indirect submission to the Royal Commission the N.H.S. Dr Elwood (Sept. 25, p. 677) makes some telling
points. The well-referenced sections on efficiency and effectiveness must, as he indicates, be logically followed by a paragraph on rationing. The first section on prescribing, is in complete contrast, however. Dr Elwood implies that pharmaceutical costs are excessive. This is supported by the charges that pharmaceutical firms, through their promotional activity, can reinforce doctors’ "indifference" to prescription price, and that to do so they merely need to satisfy the "general practitioner that a particular product is prescribable on form E.c.10". It is hard to see the rationale for such an emphasis on pharmaceuticals. A third of Dr Elwood’s article is devoted to prescribing while medicaments (including pharmacists’ fees and margins) account for only 11-12% of total N.H.S. costs.’ The solitary reference given in this part of the article is a (correct) definition of cost. True cost is the alternative foregone to obtain something. In this context it is useful to point out that in 1975 a prescription cost on average 130p including dispensing fees. If this prevented hospital admission, it would have resulted in a saving of £150, the cost of caring for one patient during an average stay in hospital in that year.2 Recent empirical work of my own has provided results strikingly opposed to Dr Elwood’s unsubstantiated assertions.3 I examined all new chemical entities introduced on to the U.K. prescription medicine market between 1962 and 1970. The products had already been rated qualitatively by therapeutic importance at date of launch by a panel of clinical and pharmacological experts.4 This information was compared with their respective daily dosage costs (relative to close substitutes) and with their achieved levels of sales. The results cannot be reproduced in detail here but in essence the view that prices are ineffectively regulated by market forces received no support. In pricing new products firms have to consider carefully the relative prices and merits of alternatives if they are to gain prescriber allegiance. A third of all new products were introduced at lower prices than existing substitutes. Only innovations of "major clinical significance" or those providing "substantial advantages for a majority of patients" were likely to be both highly priced and successful. Even innovations of this degree of importance tended to be priced from the start at low levels if a superseding innovation (which the original innovator presumably anticipated) appeared within two years of initial product launch. Firms do not behave in this sort of manner arbitrarily. They do so because if they did not, their competitors would take business from them by attracting their customers (the doctors) with a more efficacious and economic product. Moreover, not only are doctors apparently not price "indifferent" but promotion cannot sell a low-priced product even if it is "prescribable on form E.c.10". Minor innovations were generally successful only when priced low, but even a low price could not prevent most "marginal" and "near identical" advances from being commercial failures. The indictment which Dr Elwood makes against doctors when he argues that they should be "more cost conscious ... more sensitive to the issue of efficiency... and more questioning in the assessment of the effectiveness of what they are doing" seems unwarranted. Doctors seem already to be all of these things, at least in the area of pharmaceutical prescription. Department of Business Studies, University of Edinburgh, Edinburgh EH8 9JY
Department of Health and Social Security
W. DUNCAN REEKIE
Annual Reports. H.M. Stationery Office. 2. ibid. 3. Reekie, W. D. Pricing New Pharmaceutical Products. London, 1976. 4. Innovative Activity in the Pharmaceutical Industry. National Economic Development Office, 1973.
SIR,-We agree with Dr Frayn and Dr Heath (Aug. 21 427) that control of glucose utilisation is more important maintaining a set plasma-glucose. They do not, however, cate how the body might assess or regulate "normal" glucose utilisation or maintain the "necessary" raised fasting plasmaglucose of diabetes. We submit that both could be achieved . the hepatic/beta-cell feedback loop.’ In insulin-deficienc a states, this loop provides a compensatory basal hyperglycæmia to stimulate normal (or theoretically slightly subnormal basal insulin levels, whereas if there were hepatic insulin resistance. the basal plasma-insulin would be increased (as is found in obesity and insulin receptor deficiency2). Thus, despite insulin deficiency or resistance, a near-normal effective action of insulin is maintained in the fasting state. This, together with substrate control of fuel utilisation,° allows a more or less normal flux of metabolites, including glucose, aminoacids, and free fatty acids. Whilst the plasma-glucose is a major determinant of the fasting insulin concentration, the "stability" of the effective basal insulin concentration has wider implications than the control of glucose utilisation. Dr Frayn and Dr Heath, citing Reaven’s group,5 assume that the hyperglycaemia of diabetes is primarily due to penpheral insulin resistance. Reaven and his colleagues now suggest that a decreased "efficiency" of peripheral glucose uptake confirms this postulate.** However, their diabetics had higher plasma-glucose concentrations, and also greater absolute penpheral glucose uptakes than the normal subjects. The glucose uptakes were approximately appropriate for the different glucose concentrations at the same insulin concentration.’ 8 Thus an alternative interpretation of Reaven’s results would be that their diabetics’ hyperglycæmia was predominantly secondan to the demonstrated increased hepatic glucose production6 (which might result from a decreased insulin production capacity). Other investigators suggest that insulin deficiency is the predominant feature of diabetes,9 10 and we find that mild diabetics of normal-weight have normal insulin sensitivity.1l-!1 Insulin resistance usually affects the liver as well as the periphery 14 11 (and this helps to maintain normal glucose utthsation). The fasting peripheral insulin levels, in diabetes, are similar to those of normal subjects of similar adiposity,16 and we suggest that this makes hepatic insulin resistance unlikelv. If there were insulin resistance solely in the periphery, we suggest it would increase fat mobilisation and promote muscle free-fatty-acid utilisation (perhaps even producing lipoatrophy), but that the hepatic/beta-cell feedback loop would mamtain only slightly raised glucose and insulin concentrations.A complex control mechanism would be required for peripheral insulin resistance to produce a high basal plasma-glucose with a normal basal insulin concentration. R. C. TURNER Nuffield Department of Clinical Medicine Radcliffe Infirmary, Oxford OX2 6HE R. R. HOLMAN 1. Turner, R. C., Holman, R. R. Lancet, 1976, i, 1272. 2. Perley, M., Kipms, D. M. Diabetes, 1966, 15, 867 3. Kahn, C. R., Flier, J. S., Bar, R. S., Archer, J. A., Gorden, P, Martin, M. M., Roth, J. New Engl. J. Med. 1976, 294, 739. 4. Randle, P. J., Garland, P. B., Hales, C. N., Newsholme, E. A. Lancet, 1963, i, 785. 5. Shen, S. W., Reaven, G. M., Farquhar, J. W. J. clin Invest 1970, 49, 2151. 6. Kimmerling, G., Javorski, W. C., Olefsky, J. M., Reaven, G M., Diabetes, 1976, 25, 673. 7. Park, C. H., Morgan, H. E., Henderson, M. J., Regen, D. M, Cadenas, E, Post, R. L. Rec. Progr. Horm. Res. 1961, 17, 493 8. Denton, R. M., Yorke, R. E., Randle, P. J. Biochem. J 1966, 100, 407. 9. Fujita, Y., Herron, A. C., Seltzer, H. S. Diabetes, 1975, 24, 17. 10. Perley, M. J., Kipnis, D. M. J. clin. Invest. 1967, 46, 1954 11. McCarthy, S. T., Harris, E., Turner, R. C. Diabetologia (in the press). 12. Turner, R. C., Harris, E., Ounsted, M., Ponsford, C. Unpublished. 13. Turner, R. C., McCarthy, S. T., Holman, R. R., Harris, E. Br med. J. 1976, i, 1252. 14. Felig, P., Wahren, J. in Contemporary Topics in the Study of Diabetes and Metabolic Endocrinology (edited by E. Shafrir), p 2. New York, 1975. 15. Soll, A. H., Kahn, C. R., Neville, D. M., Roth, J. J. clin Invest. 1975, 56, 769. 16. Porte, D., Bagdade, J. D., Lerner, R. L. Excerpta med. int Congr. Ser. 1971, no. 231, p. 544.