Monday, 3 September 2012

The Will Rogers Phenomenon

William Penn Adair "Will" Rogers (November 4, 1879 – August 15, 1935) was an American cowboy, performer, humorist, social commentator and motion picture actor. He was one of the world's best-known celebrities in the 1920s and 1930s. 

The Will Rogers phenomenon is obtained when moving an element from one set to another set raises the average values of both sets. It is based on the following quote, attributed (perhaps incorrectly) to Will Rogers: "When the Okies left Oklahoma and moved to California, they raised the average intelligence level in both states."

The effect will occur when both of these conditions are met:

  1. The element being moved is below average for its current set. Removing it will, by definition, raise the average of the remaining elements.
  2. The element being moved is above the current average of the set it is entering. Adding it to the new set will, by definition, raise the average.

OBJECTIVE: Using different criteria for classifying MSers into various stages of a disease can modify the stage-specific prognosis, even though the overall disease course remains unchanged. This is known as the "Will Rogers phenomenon," precluding the use of historical controls for treatment trials. We assessed whether the Will Rogers phenomenon may affect MS prognosis when applying different diagnostic criteria.

METHODS: CISers with a clinically isolated syndrome (CIS) suggestive of MS were studied. After 1 year, each patient was classified as CIS or evolved to MS according to two diagnostic criteria (Poser and McDonald). The outcome for prognosis was the time to reach an Expanded Disability Status Scale score > or = 3.0.

RESULTS: 309 MSers were studied for a median period of 84 months. After 1 year, 16% of patients had MS according to Poser and 44% according to McDonald criteria. The probability to reach Expanded Disability Status Scale score > or = 3.0 at median follow-up was 11% in CISers according to Poser and 7% according to McDonald criteria; it was 46% in MSers according to Poser and 27% acccording to McDonald criteria. The group with a discordant diagnosis had a worse prognosis than that of CISers according to both criteria (p = 0.01), but better than that of MSers according to both criteria (p = 0.01).

INTERPRETATION: The use of different diagnostic criteria may generate spurious improvements in the medium-term prognosis of MS. This calls for caution in using historical controls for MS trials.


"The Will Rogers Phenomenon has occurred as the more active CISers are taken out of the CIS group and added to the MS group. This improves the outcome of both groups because the CISers left behind in the CIS group are more benign and it improves the MS group as the CISers that have been moved from CIS to MS are less active than the old MS group. 


As a result of the Will Rogers Phenomenon we cannot use historical controls for MS trials. Each change in the diagnosis of MS alters the prognosis. Therefore in clinical trials we need contemporary placebo of control groups. I hope this posting is clear?"

4 comments:

  1. "Contemporary placebo of control groups" - I understand where you are coming from on this - but can't you also suggest that other measures can be taken into consideration that reduce the reliance on active versus placebo testing styles?

    A previous post talked about neurofilaments as indicators of progression.

    Could new DMTs be assessed on their impact on NF or other measures - that would be 'above' the placebo effect?

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  2. There is some hidden positive news within this research. Based on the McDonald criteria, 73% of MSers will be EDSS 2.5 or below (which is fully ambulatory - mild disability in one functional system or minor in two) after 8 years. 93% of those with a CIS diagnosis can expect the same outcome. In fact, those diagnosed under the 2010 McDonald criteria can expect a better statistical prognosis as this widened the definition and would thus have had an even further Will Rogers effect.

    Caveat: Yes, EDSS has its limitations and, yes, some people will fare much more badly than this (that's why it's not 100%) but for fairly newly diagnosed people thinking their life is over with immediate effect, this is a further example of the fact that the pace of disability progression is often slower than people believe when facing their MS fears.

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  3. i need to know how many oligoclonal bands need to be present for the diagnosis of ms

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    Replies
    1. By definition oligoclonal means 2 or more bands. Monoclonal refers to one!

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