临床试验：临床终点(2)

Endpoints by different measure methods

Clinical endpoints can be categorized as quantitative or qualitative depending on how the outcome is measured.

• Quantitative endpoints are measured objectively by the amount of time that has elapsed from randomization or treatment initiation to the desired event.
• Qualitative endpoints are measured subjectively and are typically reported based on observations made by the patient, caregiver, or physician.

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Endpoints for late phase trials

Endpoints for late phase trials can be broadly classified as either clinical or non-clinical.

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Clinically meaningful endpoints

Clinically meaningful endpoints that directly measure how a patient feels, functions, or survives. Direct endpoints in themselves represent or characterize the clinical outcome of interest:

  感觉（feels）是指患者的身体感觉（例如症状）或感知的心理状态，患者可能感觉到的疼痛、发热或感到严重的情绪低落（如同抑郁一样）等。
  功能（function）是指患者成功的执行一项任务方式和在必需的日常生活中发挥的作用，患者完成日常生活中的一项任务专门活动所表现出的特定的能力（如，如厕、穿衣等）。
  生存（survives）是指患者疾病最终结局如生存期、残疾、功能丧失和某些重要的临床事件（如，心梗、骨折）等生存状况水平和特点，指那些对患者影响最大、最直接、患者最关心、最想避免的临床事件。

These endpoints may be measured objectively or subjectively,

• Objective: survival, disease exacerbation, clinical event (e.g. MI, stroke), etc.
• Subjective: symptom score, “health related quality of life” (validated instrument), etc.

and are either :

• reported by clinicians (ClinRO), which involves judgement or interpretation of clinical signs or events (such as stroke, myocardial infarct or cancer remission),

• assessed by standardised performance measures (6-min walk test),

• patient-reported (PRO), which are directly reported by patients (such as self-reported symptoms or function, or a measure of perceived quality of life)

• observer-reported (ObsRO), such as a parent log of seizure activity in a child

Non-clinical endpoints

Non-clinical endpoints, including biomarkers, do not relate directly to how a person feels, functions or survives, but are instead objectively measured indicators of a biological or pathogenic process, for example a pharmacological response to a treatment intervention.

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Endpoints in cancer clinical trials

Patient-centered clinical endpoints

• Overall survival
• Health-related Quality of life (QoL)
  QoL could be considered as a patient-defined measure using the WHO health definition of QoL. QoL reflects direct clinical benefit of treatments for the patient.

Tumor-centered clinical endpoints

• Tumor-centered clinical endpoints include biological markers. In most oncologic clinical trials, these endpoints include laboratory or histology markers to define response to a therapeutic intervention. For instance, tumor response (RECIST), circulating tumor cells, disease-free survival (DFS) and progression-free survival (PFS) are tumor-centered clinical endpoints.

• Surrogate endpoints are tumor-centered clinical endpoints that can be used as substitutes for patient-centered clinical endpoints,

参考资料

1. Delgado, A., & Guddati, A. K. (2021). Clinical endpoints in oncology - a primer. American journal of cancer research, 11(4), 1121–1131.
2. McLeod, Charlie et al. “Choosing primary endpoints for clinical trials of health care interventions.” Contemporary clinical trials communications vol. 16 100486. 12 Nov. 2019.
3. Fiteni, F et al. “Endpoints in cancer clinical trials.” Journal of visceral surgery vol. 151,1 (2014): 17-22.
4. Kilickap, Saadettin et al. “Endpoints in oncology clinical trials.” Journal of B.U.ON. : official journal of the Balkan Union of Oncology vol. 23,7 (2018): 1-6.