WIKI的疫苗實驗說明

【縛雞之見】
以下是WIKI的資料
第一階段：主要為了檢測安全性（無嚴重不良事件SAE）和免疫反應的證據（抗體產生），並以統計方式觀察顯著性。逐漸增量，以找出臨界值。
第二階段：擴大實驗對象
第三階段：在自然環境下觀察毒性、免疫原性和SAE，證明安全、有效（有注射者較不會得病、無注射者較會得病），之後發證
第四階段：獲得許可和上市後，不斷收集有關疫苗使用、不良反應和長期免疫力的資訊，以調整銷售、適用範圍等。

Phase I

The Phase I study consists of introducing the vaccine candidate to assess its safety in healthy people. A vaccine Phase I trial involves normal healthy subjects, each tested with either the candidate vaccine or a "control" treatment, typically a placebo or an adjuvant-containing cocktail, or an established vaccine (which might be intended to protect against a different pathogen). The primary observation is for detection of safety (absence of an adverse event) and evidence of an immune response.

第一階段的研究包括引入候選疫苗，以評估其在健康人群中的安全性。疫苗第一階段試驗涉及正常的健康受試者，每個人都用候選疫苗或 "對照 "治療，通常是安慰劑或含有佐劑的雞尾酒製劑，或已建立的疫苗（可能是為了防止不同的病原體）進行測試。主要的觀察是為了檢測安全性（無不良事件）和免疫反應的證據。

After the administration of the vaccine or placebo, the researchers collect data on antibody production, on health outcomes (such as illness due to the targeted infection or to another infection). Following the trial protocol, the specified statistical test is performed to gauge the statistical significance of the observed differences in the outcomes between the treatment and control groups. Side effects of the vaccine are also noted, and these contribute to the decision on whether to advance the candidate vaccine to a Phase II trial.

在注射疫苗或安慰劑後，研究人員收集關於抗體產生、健康結果（如由於目標感染或其他感染引起的疾病）的資料。按照試驗方案，進行指定的統計測試，以衡量治療組和對照組之間觀察到的結果差異的統計意義。疫苗的副作用也會被注意到，這些有助於決定是否將候選疫苗推進到第二階段的試驗。

One typical version of Phase I studies in vaccines involves an escalation study, which is used in mainly medicinal research trials. The drug is introduced into a small cohort of healthy volunteers. Vaccine escalation studies aim to minimize chances of serious adverse effects (SAE) by slowly increasing the drug dosage or frequency.^[5] The first level of an escalation study usually has two or three groups of around 10 healthy volunteers. Each subgroup receives the same vaccine dose, which is the expected lowest dose necessary to invoke an immune response (the main goal in a vaccine – to create immunity). New subgroups can be added to experiment with a different dosing regimen as long as the previous subgroup did not experience SAEs. There are variations in the vaccination order that can be used for different studies. For example, the first subgroup could complete the entire regimen before the second subgroup starts or the second can begin before the first ends as long as SAEs were not detected. The vaccination schedule will vary depending on the nature of the drug (i.e. the need for a booster or several doses over the course of short time period). Escalation studies are ideal for minimizing risks for SAEs that could occur with less controlled and divided protocols.

疫苗I期研究的一個典型版本涉及升級研究，主要用於藥物研究試驗。藥物被引入一小群健康志願者中。疫苗升級研究旨在透過緩慢增加藥物劑量或頻率，將嚴重不良反應（SAE）的機率降至最低。每個亞組接受相同的疫苗劑量，這是引起免疫反應（疫苗的主要目標--產生免疫力）所需的預期最低劑量。只要前一個子組沒有出現SAE，就可以增加新的子組來試驗不同的劑量方案。疫苗接種順序有變化，可用於不同的研究。例如，第一個亞組可以在第二個亞組開始之前完成整個方案，或者只要沒有發現SAE，第二個亞組可以在第一個亞組結束之前開始。疫苗接種計畫將根據藥物的性質而有所不同（即需要在短時間內進行強化接種或多次接種）。升級研究是將SAE的風險降到最低的理想選擇，而SAE可能發生在控制較少和劃分較少的方案中。

Phase II

The transition to Phase II relies on the immunogenic and toxicity results from Phase I in a small cohort of healthy volunteers. Phase II will consist of more healthy volunteers in the vaccine target population (~ hundreds of people) to determine reactions in a more diverse set of humans and test different schedules.

向第二階段的過渡依賴於第一階段在一小批健康志願者中取得的免疫原性和毒性結果。第二階段將由疫苗目標人群中更多的健康志願者組成（約數百人），以確定在更多的人類中的反應，並測試不同的時間表。

Phase III

Similarly. Phase III trials continue to monitor toxicity, immunogenicity, and SAEs on a much larger scale. The vaccine must be shown to be safe and effective in natural disease conditions before being submitted for approval and then general production. In the United States, the Food and Drug Administration (FDA) is responsible for approving vaccines.

同樣地。第三階段試驗繼續在更大的範圍內監測毒性、免疫原性和SAE。疫苗必須在自然疾病條件下被證明是安全和有效的，然後才能提交審批，然後進行普遍生產。在美國，食品和藥物管理局（FDA）負責批准疫苗。

Phase IV

Phase IV trials are typically monitor stages that collect information continuously on vaccine usage, adverse effects, and long-term immunity after the vaccine is licensed and marketed. Harmful effects, such as increased risk of liver failure or heart attacks, discovered by Phase IV trials may result in a drug being no longer sold, or restricted to certain uses; examples include cerivastatin (brand names Baycol and Lipobay), troglitazone (Rezulin) and rofecoxib (Vioxx).

第四階段試驗通常是監測階段，在疫苗獲得許可和上市後，不斷收集有關疫苗使用、不良反應和長期免疫力的資訊。第四階段試驗發現的有害影響，如肝衰竭或心臟病發作的風險增加，可能會導致藥物不再銷售，或限制某些用途；例子包括塞裡伐他汀（品牌名稱Baycol和Lipobay）、曲格列酮（Rezulin）和羅非克司（Vioxx）。（中文由DeepL翻譯，Taimocracy修正）