lady_express_44
10-15-2007, 01:34 PM
The Will Rogers’ phenomenon in multiple sclerosis
M. Tintoré, M.P. Sormani, *. Rovira, X. Vidal, X. Montalban, M. Filippi (Barcelona, E; Genoa, I; Milan, I)
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Introduction: In clinical medicine, it has been shown that changes in the tools/criteria used to define a diagnosis can result in spurious improvements of stage-specific prognosis without “real” change in outcome of individual patients. This is known as the “Will Rogers’ phenomenon” (WRP) and considered one of the most important biases, limiting use of historical controls in clinical trials. Since this approach looks attractive in Multiple Sclerosis (MS), where availability of disease-modifying drugs has made placebo-controlled trials ethically questionable, we assessed whether the WRP is at work also in MS. MS diagnostic criteria have seen dramatic changes over the last twenty years after the introduction of MRI in diagnostic work up.
Methods: In 1995-2001, 322 consecutive patients with a clinically isolated syndrome (CIS) at presentation suggestive of MS underwent brain MRI within 3 months of clinical onset and 12 months and 5 years later. Number and location of lesions on baseline MRI and the development of new T2 lesions at follow up were evaluated. Based on the information from 12 months from onset, patient were classified according to two different diagnostic criteria (“Poser”–P– and “McDonald”–McD) as still CIS or evolving to MS. Prognosis was defined as time needed to reach EDSS?3; Cox model and Kaplan Meier survival curves were used to compare prognosis of CIS and MS according to each set of criteria. Concordant and discordant diagnoses between the P and McD criteria were also studied.
Results: 309 patients were included and clinically followed for a median of 84 months. At 1 year, 16% of patients were diagnosed with MS according to the P criteria and 44% according to the McD. An improved prognosis was seen in both groups (CIS and MS) for patients classified according to McD criteria compared to P: probability to reach EDSS=3 at year 8 was 15% in CIS patients according to P, 9% in CIS patients according to McD, 52% in MS patients according to P, and 34% in MS patients according to McD. The group with discordant diagnosis had worse prognosis than patients classified as CIS by both criteria (HR=2.5, 95%CI=1.2-5.1, p=0.014), and better than patients classified as MS by both criteria (HR=0.42, 95%CI=0.22-0.82, p=0.01).
Conclusions: These observations support the hypothesis that “stage migration” may cause over time spurious improvements in the prognosis of MS (WRP) and call for caution using historical control groups in clinical trials.
http://registration.akm.ch/einsicht.php?XNABSTRACT_ID=53477&XNSPRACHE_ID=2&XNKONGRESS_ID=63&XNMASKEN_ID=900
The Will Rogers Phenomenon:
http://en.wikipedia.org/wiki/Will_Rogers_phenomenon
Cherie
M. Tintoré, M.P. Sormani, *. Rovira, X. Vidal, X. Montalban, M. Filippi (Barcelona, E; Genoa, I; Milan, I)
--------------------------------------------------------------------------------
Introduction: In clinical medicine, it has been shown that changes in the tools/criteria used to define a diagnosis can result in spurious improvements of stage-specific prognosis without “real” change in outcome of individual patients. This is known as the “Will Rogers’ phenomenon” (WRP) and considered one of the most important biases, limiting use of historical controls in clinical trials. Since this approach looks attractive in Multiple Sclerosis (MS), where availability of disease-modifying drugs has made placebo-controlled trials ethically questionable, we assessed whether the WRP is at work also in MS. MS diagnostic criteria have seen dramatic changes over the last twenty years after the introduction of MRI in diagnostic work up.
Methods: In 1995-2001, 322 consecutive patients with a clinically isolated syndrome (CIS) at presentation suggestive of MS underwent brain MRI within 3 months of clinical onset and 12 months and 5 years later. Number and location of lesions on baseline MRI and the development of new T2 lesions at follow up were evaluated. Based on the information from 12 months from onset, patient were classified according to two different diagnostic criteria (“Poser”–P– and “McDonald”–McD) as still CIS or evolving to MS. Prognosis was defined as time needed to reach EDSS?3; Cox model and Kaplan Meier survival curves were used to compare prognosis of CIS and MS according to each set of criteria. Concordant and discordant diagnoses between the P and McD criteria were also studied.
Results: 309 patients were included and clinically followed for a median of 84 months. At 1 year, 16% of patients were diagnosed with MS according to the P criteria and 44% according to the McD. An improved prognosis was seen in both groups (CIS and MS) for patients classified according to McD criteria compared to P: probability to reach EDSS=3 at year 8 was 15% in CIS patients according to P, 9% in CIS patients according to McD, 52% in MS patients according to P, and 34% in MS patients according to McD. The group with discordant diagnosis had worse prognosis than patients classified as CIS by both criteria (HR=2.5, 95%CI=1.2-5.1, p=0.014), and better than patients classified as MS by both criteria (HR=0.42, 95%CI=0.22-0.82, p=0.01).
Conclusions: These observations support the hypothesis that “stage migration” may cause over time spurious improvements in the prognosis of MS (WRP) and call for caution using historical control groups in clinical trials.
http://registration.akm.ch/einsicht.php?XNABSTRACT_ID=53477&XNSPRACHE_ID=2&XNKONGRESS_ID=63&XNMASKEN_ID=900
The Will Rogers Phenomenon:
http://en.wikipedia.org/wiki/Will_Rogers_phenomenon
Cherie