Rapid Responses to:

LETTERS: Sally C Davies and Marilyn Roberts-Harwood European register of patients with sickle cell disease treated with hydroxyurea is being set up BMJ 1998; 317: 541a [Full text]

Rapid Responses: Submit a response to this article

Rapid Responses published:

EUROPEAN REGISTER OF PATIENTS WITH SICKLE CELL DISEASE

Ade Olujohungbe   (29 September 1998)

EUROPEAN REGISTER OF PATIENTS WITH SICKLE CELL DISEASE 29 September 1998
Ade Olujohungbe, SENIOR REGISTRAR CHRISTIE HOSPITAL Send response to journal: Re: EUROPEAN REGISTER OF PATIENTS WITH SICKLE CELL DISEASE	Authors' reply: EDITOR: We welcome the launch of a European register of patients with sickle cell disease treated with hydroxyurea, and will certainly offer anonymised details of our treated patients. However, Dr Davies would be the first to agree that a register collecting data retrospectively cannot address research questions in the way that formal , prospective, controlled studies can. Dr. Davies writes that "in 1995, Charache et al showed conclusively in the US that hydroxyurea ameliorates the clinical consequences of most patients", and certainly the results of that excellent study (1) were most convincing. However, there is marked clinical heterogeneity in this condition , and it cannot be assumed that the outcome would necessarily be identical in a different study population. Although the genotypes of patients in the USa are not likely to differ radically from those in the UK, it is important to recognise the extent to which the clinical phenotype in this disease can be influenced also by previous pain management experience and other social and enviromental as confirmed by the study " Living with Sickle Cell" (2), and this might give rise to differences in outcome. Further, while the US study demonstrated clearly the effectiveness of hydroxyurea in reducing pain episodes and certain other complications in that study population, of course it could not address all the questions concerning its use. For example, is maximum tolerated dose necessary for maximum clinical benefit, is daily dosing more effective than intermittent dosing and would toxicity be reduced by the latter, what agents given together with hydroxyurea augment clinical response? We entirely agree that these major clinical research questions need to be addressed by a collaborative approach between centres and we look forward to seeing this established in the UK. However, even then, recruitment may still be an issue as we have outlined. If a large centre such as Brent can only accrue 10 patients slowly, we will have to wait a long time before the Uk is going to make any contribution towards answering these important clinical questions. It should not be assumed that failure to recruit patients is necessarily indicative of poor study design or lack of an appropriate clinical question. Our failed studies were emphatically not designed 'to familiarise clinicians with hydroxyurea'. For example, at the North Middlesex Hospital, our pilot study was designed to look at the possibility that recombinant human GM-CSF might augment the response to hydroxyurea, as might theoretically be expected. There was a clear research question and we were most careful to articulate it sensitively and fully to our patients, but we recruited only 4 of the 20 we had hoped to. A.Yardumian, Consultant Haematologist, North Middlesex Hospital, London N18. A. Olujohungbe, Senior Registrar in Haematology, Manchester Royal Infirmary. K. Cinkotai, Associate Specialist in Haematology, Manchester Royal Infirmary. (1) Effect of Hydroxyurea on the frquency of painful crisis in sickle cell anaemia. Charache S, Terrin ML, Moore DR et al New England Journal of Medicine 1995, 332: 1317-22 (2) 'Living with Sickle Cell' Maxwell K, Streely A Public Health Department of Guy's and St. Thomas' Hospital; work in progress, presented at Kings Fund 5.2.98.