I thank the Economic and Social research Council for funding this research and who provided me with a wonderful opportunity to pursue my PhD. I am extremely grateful to my supervisor, Professor Alan Brennan, for all his support, guidance and contributions to this work. His enthusiasm for the project have been motivating and inspiring throughout the PhD. I would like to thank my second supervisor Jeremy Oakley for his technical support and for comments on my thesis. I would like to acknowledge the help and assistance provided by the staff in ScHARR during the course of this study. I would like to extend particular thanks to Mark Strong for providing technical support throughout the PhD and who provided invaluable support in using Iceberg. All through my PhD I have been fortunate to have worked alongside PhD students who have provided a brilliant support and friendship network. I would like to extend particular thanks to Jenny Willson, Carl Tilling, Will Sullivan, Kiera Bartlett, Brian Reddy, and Paul Richards, for creating a helpful, amusing and positive work environment. I would also like to thank all my friends and family for their continuing love and assistance. I thank my sister Naomi for her support and advice. I must acknowledge the invaluable emotional support, contribution, and proof-reading from my father Peter, and my partner Jonathan. In sadness I thank and remember my mother Jan, whose love and encouragement have always been the greatest inspiration to me.
Table : Odds ratios and hazard ratios with confidence intervals estimated for risk factors for neuropsychiatric damage Author name Date Damage outcome Disease Activity Ethnicity anticardiolipids Organ damage Steroid Anti-malarials Diabetes Age Hypertension Mikdashi (184) 2004 Neuropsychiatric damage (OR) 2.7 (1.0-6.7) 3.0 (1.0-19.5) 4.8 (1.0-23.0) Mok (185) 2006 Neuropsychiatric damage (HR) 1.28 (1.29-1.31) 1.16 (1.10-1.23) Gonzalez (186) 2009 Neuropsychiatric damage (HR) 1.16 (1.12–1.21) 1.87 (1.22–2.87) 0.56 (0.35–0.92) 0.58 (0.36–0.93) 3.47 (1.44–8.38) Mikdashi (187) 2005 Seizures(OR) 2.29 (1.01-1.12) 2.23 (1.01–4.67) Andrade (188) 2008 Seizures (HR) 1.10 (1.04- 1.15) 2.7 (1.3–5.7) 0.35 (0.15- 0.80) 1.04 (1.00-1.08) (189) 2008 Seizure (HR) 1.0 (0.9–1.0) Mikdashi (190) 2007 Stroke (HR) 1.31 (0.40-4.31) 1.11 (0.43–2.84) 1.00 (0.98–1.03) 2.31 (1.15–4.65) HR Hazard ratios, OR Odds ratios; aCL anticardiolipin antibodies
The evidence from suggests that gastrointestinal damage occurs in a very small proportion of SLE patients. and Figure 9 show that gastrointestinal system damage occurs early in the disease. The rate of damage accrual after the first year of the disease is relatively low. illustrates that damage in the musculoskeletal system is common in SLE patients. Petri et al. (170) find that avascular necrosis (osteonecrosis) as the most common musculoskeletal complication in SLE patients affecting 14.5% of patients. Table 18 reports the odds ratios for logistic regression for musculoskeletal damage and related events. Table : Odds ratios with confidence intervals estimated for risk factors for musculoskeletal damage First Author name Date Damage outcome Disease Activity Age Steroids Immunosuppressants Arthritis Stoll (179) 2001 Musculoskeletal damage (OR) 2.26 (0.65–10.32) 0.885 (0.78–1.00) Gladman (199) 2001 Osteonecrosis (OR) 18.5 (3.2-359.6) 2.7 (1.02-8.8) 4.2 (1.6-13.7) (200) 2006 Osteonecrosis (OR) 1.03 (1.00-1.05) 3.04 (1.02 OR Odds ratios
uncertain of the long term outcomes for patients receiving treatment. 9 What difference do you think there could be in the number of patients who have cardiovascular, neuropsychiatric, or gastrointestinal damage after 5 years of biologic treatment compared with the natural history predictions. In this question reductions in damage risk due to lower disease activity scores and steroid dose have been adjusted for. Expert 1 did not believe that additional benefit to damage would be observed. Expert 2 was uncertain about the effect of treatment. Expert 3 expected large reductions in organ damage, but expressed uncertainty in the magnitude. Expert 4 was very uncertain of the long term outcomes for patients receiving treatment. 10 What difference do you think there could be in the number of patients who have renal, pulmonary or vascular damage after 5 years of biologic treatment compared with the natural history predictions. In this question reductions in damage risk due to lower disease activity scores and steroid dose have been adjusted for. Expert 1 did not believe that additional benefit to damage would be observed. Expert 2 believed that fewer patients would develop disease activity related damage. Expert 3 expected improvements in disease activity related organ damage. Expert 4 was uncertain of the effect of treatment on damage. 11 What difference do you think there could be in the number of patients who have musculoskeletal damage, ocular damage or diabetes after 5 years of biologic treatment compared with the natural history predictions. In this question reductions in damage risk due to lower Expert 1 believed that additional benefit to damage caused by steroids would be observed. Expert 2 believed that treatment was less likely to improve outcomes than the predictions. Expert 3 was very uncertain of the effects of treatment on steroid related damage. Expert 4
Table : Summary of elicitation methods used Study Selection of participants Number of participants Survey or face to face Pre-elicitation training of participants Elicitation technique Synthesis Soares (2010) Nurses with knowledge and experience of patient management 23 Group face to face A talk on the concepts and questions covered in the exercise and example exercises. Histogram with discrete numerical scale. Respondents used 21 crosses to express distribution. Linear pooling with equal weights. Harmanec (1999) Doctors Not reported Not reported Not reported Doctors reported point estimate probabilities Not reported Garthwaite (2008) Medical experts with experience in a range of issues in the decision model 4 Face to face An outline of the questions to be asked, and consultation on what covariates to include. Median and quartile selection with covariates. The model uses one response from an expert and uncertainty in increased if other experts have different responses. Leal (2007) Genetic experts and cardiologists. Experts were selected from different geographic locations in the UK 7 Questionnaire and face to face An email explaining the goal of the questionnaire. Four complimentary intervals. Linear pooling with equal weights. McKenna (2010) Experience and clinical knowledge in the UK. 5 Questionnaire Not reported Frequency chart. Respondents used 20 crosses to express distribution. Linear pool with equal weights. Boike (2009) Senior rheumatologist with experience of disease activity index used in the model. 5 Questionnaire Not reported Histogram with a discrete numerical scale. Respondents used 20 crosses to express distribution. Linear pool with weights derived calibration questions and random effects Lau (1999) Physicians. 2 Face to face Document outlining the objectives, description of cognitive heuristics and biases and other relevant issues was read by expert. Techniques include sample distribution, the betting and the likelihood method. Not reported