Reply

J. A. Snowden and P. M. Brooks1

Department of Haematology, Leicester Royal Infirmary, Leicester, UK and
1 Faculty of Health Sciences, University of Queensland, Brisbane, Australia

We read with interest the correspondence of Ho and Pullar and of van Laar et al. and welcome their contribution to the discussion of our article [1]. Risk taking in rheumatoid arthritis (RA) has been previously explored by a number of workers including Ho and Pullar [25]. We decided to revisit this area as the issue of haemopoietic stem cell transplantation (HSCT) forces the patient and doctor to trade the possibility of substantial efficacy against a defined risk of early treatment-related mortality (TRM). The standard gamble used in our study was deliberately simple, i.e. ‘return to normality off all medication’ vs death. The standard gamble was neither a description of the complex process of HSCT nor did it attempt to incorporate any predictions for outcome from autologous HSCT, which at the time of the study were unknown. We chose ‘a cure all, reverse all’ outcome as it is often impossible to quantify the potential reduction in disability by removing the active component of RA and to separate concurrent pathology in RA patients, e.g. cardiovascular disease in the long-standing steroid-dependent RA patient with obesity, immobility, diabetes and hypertension. We found that an unselected group of 53 RA patients were prepared to risk a median of 5% chance of death to be returned to normality off all medication for the rest of their lives and that the level of risk taking was related to disability and younger age. With these considerations in mind, the study was useful in showing that some RA patients, possibly the younger and more disabled, might accept risks in the order of the TRM of autologous HSCT to be free of their disease.

Compared with our study and others that have used standard gambles [13], the studies cited by Ho and Pullar draw markedly different conclusions. This is possibly due to methodological differences; in particular, the use of a logarithmic scale. For example, in their studies, the median acceptable risk of death for cure was 1 in 100 000, a risk far less than the risk of treatment associated with, for example, non-steroidal anti-inflammatory drugs [4, 5]. There are also some apparent inconsistencies, such as the greater acceptability of risks for hip surgery than for a curative procedure [5]. They attribute this to patients having difficulty with the concept of cure, but it might be more explicable by difficulties or bias in the use of a logarithmic scale, which, arguably, incorporates ‘melodramatic’, as opposed to ‘everyday’, examples of risk taking, i.e. risk of death from lightning, bee sting, plane crash, murder, parachute jump or mountaineering. We agree with them that studies comparing both standard and logarithmic intervals would be useful to clarify the situation. However, we disagree with their statement that our median level of risk taking would change if we had more sensitively analysed the interval 0–1% as a median would remain unaffected by these values.

We agree with both Ho and Pullar and van Laar et al. that our study does not directly answer the question ‘are the risks of HSCT acceptable to patients with RA?’ and that further work is necessary to answer this question specifically. However, the acceptance of the risks by over 30 patients with severe, active and resistant RA who have been enrolled on our autologous HSCT programme [6, 7] (all after counselling from independent rheumatologists and transplant physicians), and numerous reports of other cases [812], including those of van Laar et al. above, are consistent with our findings. With increasing follow-up, the efficacy and TRM of HSCT in RA will be established and such data could form the basis for more sophisticated analyses, for example, using the Markov process [13].

References

  1. Snowden JA, Nivison-Smith I, Biggs JC, Brooks PM. Risk taking in patients with rheumatoid arthritis: are the risks of haemopoietic stem cell transplantation acceptable? Rheumatology1999; 38:321–4.[Abstract]
  2. Thompson MS. Willingness to accept risks to cure chronic disease. Am J Pub Health1986;76:392–6.[Abstract]
  3. O'Brien BJ, Elsewood J, Calin A. Willingness to accept risk taking in the treatment of rheumatic disease. J Epidemiol Commun Health1990;44:249–52.[Abstract]
  4. Pullar T, Wright V, Feely M. What do patients and rheumatologists regard as an ‘acceptable’ risk in the treatment of rheumatic disease? Br J Rheumatol1990;29:215–8.[ISI][Medline]
  5. Ho M, Lavery B, Pullar T. The risk of treatment. A study of rheumatoid arthritis patients' attitudes. Br J Rheumatol1998; 37:459–60.[ISI][Medline]
  6. Snowden JA, Biggs JC, Milliken ST, Fuller A, Brooks PM. A phase I/II dose escalation study of intensified cyclophosphamide and autologous blood stem cell rescue in severe, active rheumatoid arthritis. Arthritis Rheum1999;42:2286–92.[ISI][Medline]
  7. Moore JJ, Passuello F, The Australian Bone Marrow Transplant in Rheumatoid Arthritis Study Group. Peripheral blood stem cell transplantation for rheumatoid arthritis—the Australian multicentre randomised trial. Blood1999;94(Suppl. 1);354a.
  8. Joske DJL, Ma DT, Langlands DR, Owen ET. Autologous bone marrow transplantation for rheumatoid arthritis. Lancet1997; 350:338.[ISI][Medline]
  9. Durez P, Toungouz M, Schandene L, Lambermont M, Goldman M. Remission and immune reconstitution after T-cell-depleted stem-cell transplantation for rheumatoid arthritis. Lancet1998;352:881.[ISI][Medline]
  10. Burt RK, Georganas C, Schroeder J et al. Autologous hematopoietic stem cell transplantation in refractory rheumatoid arthritis. Arthritis Rheum1999;42:2286–92.[ISI][Medline]
  11. Pavletic ZS, O'Dell JR, Bishop MR, Kessinger A, Reed EC, Ursick MM et al. Treatment of refractory rheumatoid arthritis utilizing an outpatient autologous blood stem cell transplantation protocol. Blood1998;92(Suppl. 1):370b.
  12. Bingham S, Veale DJ, Reece R, Fearon U, McGonagle D, Morgan G et al. Autologous stem cell transplantation for severe rheumatoid arthritis—dramatic clinical, laboratory and arthroscopic results. Arthritis Rheum1999;42(Suppl.):S76.
  13. Pauker SG, Kassirer JP. Decision analysis. N Engl J Med1987;316:250–8.[ISI][Medline]
Accepted 20 December 1999





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