●Xさん(http://www.ashida.info/blog/2009/11/_1bms_2.html#more)への返信 from P｡
｢再発期間(duration of relapse)｣の定義についてですが､多施設の共同研究ですから､Xさんがご指摘の通り何らかの基準を策定しているはずです｡
この定義について論文で述べられているところは：
Relapses were defined according to the criteria of Schumacher et al.,(24) and the definition of both relapse and remission were consistent with those used in the North American study in RRMS. When a relapse occurred, the date of occurrence and duration (time to remission), the peak EDSS and NRS scores, and corresponding neurologic changes were recorded.
と書いてあります｡従って､Schumacherの基準による､再発(relapse)と寛解(remission)の間(time to remission)が､｢再発期間｣として算定されていることになります｡
Schumacherの論文は1965年に発表されていますが､時間がなく通読できませんでしたが､ざっと見ると､下記の項目のようです｡原著では"period of worsening(relapse)"と書かれています｡
(1) Period of worsening (relapse): This phase represents the period of development of a new symptom or group of symptoms or the period of aggravation of an existing symptom or symptoms if the course has been stationary or improving during the previous one month. To be counted as a separate period of worsening or relapse, the period must last at least 24 hours or longer. In any instance, symptomatic worsening should be counted as a relapse only if it is accompanied by an appropriate change in objective neurologic function as determined by examination.
The duration of a period of worsening is the time elapsing from the beginning of the worsening until symptoms and signs reach their maximum. If symptoms progress after a stationary or improving period of less than one month, this time period is included as part of the duration of the episode of worsening.
The latter qualification seems important to avoid the danger of recording minor changes in the course of downhill progression, noted from week to week, as separate relapses or new episodes of disease, thus giving a falsely high numerical score for the relapse rate if this is calculated.
In order to utilize relapse rates as a reflection of the course of illness, the attempt must be made to distinguish between minor and questionable degrees of progression and the abrupt flare-ups of disease activity generally implied by the term “relapse.” The course reflected by the temporal aspects of disease activity will probably be better shown, however, in the statistical tabulation of the duration of periods of worsening, than merely in their number.
つまり､｢再発期間｣とは､"The duration of a period of worsening is the time elapsing from the beginning of the worsening until symptoms and signs reach their maximum."であると定義されているようです｡
従って､｢再発期間｣とは症状増悪が始まった日から､その症状がﾋﾟｰｸとなった日までの期間ということです｡
症状増悪が始まった日は概ね分かることが多いとしても､既に神経学的後遺症を持っている患者さんに新しい症状が付け加えられ､それに対して急性期治療としてｽﾃﾛｲﾄﾞﾊﾟﾙｽなどを行っているときに､｢この日が症状のﾋﾟｰｸ｣と断定できるかどうかは､症状の種類にもよるかと思いますが必ずしも容易でないと思われます｡
例えば感覚障害などの場合です｡そもそも再発･寛解というのは必ずしもON-OFFのように明白に分かるものではなく(本疾患の掲示板をみると､｢これは再発でしょうか?｣という疑問が絶えない)､多くは連続的なものです｡
従ってSchumacherの基準のみで定義しているとすれば､｢再発期間｣の数値は観察者のﾊﾞｲｱｽを排除できず､さらにblindedで臨床試験を組んでいないので､ﾊﾞｲｱｽが入り易い状況に置かれていると推定されます｡
少しでもﾊﾞｲｱｽを減らそうとすれば､毎日神経症状のｽｺｱを付けて､そのｽｺｱﾘﾝｸﾞにより定義を決めるとか､症状の評価をblindedでやるとか､いろいろ考えられなくはありません｡しかし論文にはそれ以上の記載はありませんから､かなりﾊﾞｲｱｽの入り易い状態の｢再発期間｣なのかな､と推考されます｡