人生沒有用不到的經歷

這兩天生物醫學領域有一個重要的新聞，考生不妨試圖瞭解浩鼎「解盲」的來龍去脈，因為恰巧在學測甄試前發生，可能會成為生物醫學相關領域科系的面試考題。另一個重要的觀念是利益衝突(Conflict of interest)。

藥物的臨床試驗中，為避免研究者、醫師、病人對藥物療效的過度期待，會使用雙盲試驗。病人被隨機編入對照組及實驗組，對照組給予安慰劑，實驗組給予試驗藥物。無論是病人或醫師都不知道誰使用試驗藥物(雙盲)，臨床試驗結束才進行臨床數據解盲與分析。

2000年以後最有名的解盲分析是治療肺癌的標靶藥物--艾瑞莎(Iressa)，2003年Nature Review Cancer有一篇文章：
http://www.nature.com/nrc/journal/v3/n8/full/nrc1159.html
學術網路才能看原文，若需要原文pdf檔，可寫e-mail給版主。
其中有一段：
Gefitinib (Iressa, 250 or 500 mg orally once daily) as a third-line therapy for NSCLC (non-small-cell lung cancer) has been evaluated in 142 patients with advanced NSCLC whose disease had progressed despite at least two prior chemotherapy regimens including a platinum drug and docetaxel, or who had experienced unacceptable toxicity on these agents. At the recommended dose (250 mg daily), the objective tumour response rate was 13.6%, and the median duration of objective response was 8.9 months.

Gefitinib (Iressa) has also been evaluated in combination with platinum-based chemotherapy regimens in two trials involving 2,130 chemotherapy-naive patients with advanced NSCLC. Addition of gefitinib did not demonstrate any increase, or trend towards such an increase, in tumour response rates, time to progression or overall survival.

解盲的結果發現，Iressa單獨使用或與傳統化療並用，統計學上療效有限。但在臨床上確實有個別的病人出現異乎尋常的療效，2004年答案揭曉：
http://www.nejm.org/doi/full/10.1056/NEJMoa040938
若需要原文pdf檔，可寫e-mail給版主。
BACKGROUND
Most patients with non–small-cell lung cancer have no response to the tyrosine kinase inhibitor gefitinib, which targets the epidermal growth factor receptor (EGFR). However, about 10 percent of patients have a rapid and often dramatic clinical response. The molecular mechanisms underlying sensitivity to gefitinib are unknown.

CONCLUSIONS
A subgroup of patients with non–small-cell lung cancer have specific mutations in the EGFR gene, which correlate with clinical responsiveness to the tyrosine kinase inhibitor gefitinib. These mutations lead to increased growth factor signaling and confer susceptibility to the inhibitor. Screening for such mutations in lung cancers may identify patients who will have a response to gefitinib.

大部分的肺癌病人服用Iressa都沒效，約有10%的肺癌病人腫瘤EGFR基因有突變，因而Iressa對這些病人特別有效。換句話說，Iressa的療效存在於10%的誤差之中，因此在2130個接受試驗的病人，統計上看不出顯著的療效。

浩鼎的問題在哪兒？
解盲失敗，也沒在臨床上看到個別的病人出現異乎尋常的療效。

這兩天新聞的焦點在哪兒？
簡言之就是臨床試驗的「Conflict of interest (利益衝突)」，執行臨床試驗的醫師及研究者與生技公司的共生利益會影響試驗結果的分析，因此在臨床試驗進行之前必須加以防範，以維持試驗的客觀性與準確性。
http://markliu.org/COI-1.pdf