COA (Clinical Outcome Assessment): PRO, ClinRO, PerfRO, ObsRO, eCOA, and TECOA

Clinical Outcome Assessment (COA) has triggered multiple acronyms: PRO, ClinRO, PerfRO, and ObsRO

According to FDA's website, these acronyms are defined as the following: 

PRO - patient-reported outcome

A type of clinical outcome assessment. A measurement based on a report that comes directly from the patient (i.e., study subject) about the status of a patient’s health condition without amendment or interpretation of the patient’s response by a clinician or anyone else. A PRO can be measured by self-report or by interview provided that the interviewer records only the patient’s response. Symptoms or other unobservable concepts known only to the patient can only be measured by PRO measures. PROs can also assess the patient perspective on functioning or activities that may also be observable by others. PRO measures include:

• Rating scales (e.g., numeric rating scale of pain intensity or Minnesota Living with Heart Failure Questionnaire for assessing heart failure)
• Counts of events (e.g., patient-completed log of emesis episodes or micturition episodes)

Specifically for PRO, FDA has a guidance "Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims". PRO can be further separated into generic (such as SF-36, EQ-5D, ...) and disease-specific PROs (SGRQ for COPD, PAH-SYMPACT for pulmonary arterial hypertension, ...). 

ObsRO - observer-reported outcome

A type of clinical outcome assessment. A measurement based on a report of observable signs, events or behaviors related to a patient’s health condition by someone other than the patient or a health professional. Generally, ObsROs are reported by a parent, caregiver, or someone who observes the patient in daily life and are particularly useful for patients who cannot report for themselves (e.g., infants or individuals who are cognitively impaired). An ObsRO measure does not include medical judgment or interpretation. ObsRO measures include:

• Rating scales, such as:
  • Acute Otitis Media Severity of Symptoms scale (AOM-SOS), a measure used to assess signs and behaviors related to acute otitis media in infants
  • Face, Legs, Activity, Cry, Consolability scale (FLACC), a measure used to assess signs and behaviors related to pain
• Counts of events (e.g., observer-completed log of seizure episodes)

ObsRO is often used in rare diseases, in pediatric diseases, or in diseases that the patients may lose self-control and patients can not detect the signs/symptoms on their own (such as seizure, stroke).  For patients who cannot respond for themselves (e.g., infants or cognitively impaired), observer reports should include only those events or behaviors that can be observed. As an example, observers cannot validly report an infant’s pain intensity (a symptom) but can report infant behavior thought to be caused by pain (e.g., crying). For example, in the assessment of a child’s functioning in the classroom, the teacher is the most appropriate observer. Examples of ObsROs include a parent report of a child’s vomiting episodes or a report of wincing thought to be the result of pain in patients who are unable to report for themselves.

Additional examples are OsRO-Celiac Disease Daily Symptom Diary (ObsRO-CDSD©), the Pediatric Quality of Life Inventory™,  the Edmonton Symptom Assessment System Revised (ESAS-r), ....

ClinRO - clinician-reported outcome

A type of clinical outcome assessment. A measurement based on a report that comes from a trained health-care professional after observation of a patient’s health condition. Most ClinRO measures involve a clinical judgment or interpretation of the observable signs, behaviors, or other manifestations related to a disease or condition. ClinRO measures cannot directly assess symptoms that are known only to the patient. ClinRO measures include:

• Reports of particular clinical findings (e.g., presence of a skin lesion or swollen lymph nodes) or clinical events (stroke, heart attack, death, hospitalization for a particular cause), which can be based on clinical observations together with biomarker data, such as electrocardiogram (ECG) and creatine phosphokinase (CPK) results supporting a myocardial infarction
• Rating scales, such as:
  • Psoriasis Area and Severity Index (PASI) for measurement of severity and extent of a patient’s psoriasis
  • Hamilton Depression Rating Scale (HAM-D) for assessment of depression

The majority of neurological assessment tools are falling into this category. additional examples are INCAT (Inflammatory Neuropathy Cause and Treatment), Guillian-Barre Syndrome disability score, MRC sum score...

PerfRO - performance outcome

A type of clinical outcome assessment. A measurement based on standardized task(s) actively undertaken by a patient according to a set of instructions. A PerfO assessment may be administered by an appropriately trained individual or completed by the patient independently. PerfO assessments include:

• Measures of gait speed (e.g., timed 25 foot walk test using a stopwatch or using sensors on ankles)
• Measures of memory (e.g., word recall test) 

For example, the frequently used outcome measures such as the six-minute walking test (6MWT), cardio-pulmonary exercise test (CPET), Grip strength, ... are falling into PerfRO. 

FDA created a division "Division of Clinical Outcome Assessment (CDOA)" with a mission of Integrating the patient voice into drug development through COA endpoints that are meaningful to patients, valid, reliable and responsive to treatment."

For a scale that has not bee validated before and is intended to be used as the primary efficacy outcome measure in a clinical development program, CDER has two pathways for reviewing COAs:

• The CDER COA Qualification Program or
• Under an individual drug development program

With new technology development, we are now coming up with new terms: eCOA - electronic Clinical Outcome Assessment and TECOA - Technology Enabled COA. 

eCOA is to use electronic means to collect the COA data for example, electronic diaries. TECOA is a measurement that comes directly but passively from the patient using technology. 

eCOA has the following benefits:

• Improved protocol compliance
• Improved data integrity (real-time, timestamped entries, encrypted, protected data, and ability to integrate sources)
• decrease hidden cost of paper (monitoring & querying data entry, recruitment due to non-compliance of paper, regulatory submission risk)
• Better patient experience (intuitive user interface, ability to work offline/online, can be used on patients' devices to fit their lifestyle)
• Improved operational efficiencies (shortened study timelines, reduced manual efforts, easily make mid-study changes, gather real-time insights)
• Better regulatory guidance (regulators support and encourage eCOA use, willing to include outcomes in product labels). 

REFERENCES:

• Benjamin et al (2017) Patient-Reported Outcome and Observer-Reported OutcomeAssessment in Rare Disease Clinical Trials: An ISPOR COAEmerging Good Practices Task Force Report
• Powers et al (2017) Clinician-Reported Outcome Assessments of Treatment Benefit: Report of the ISPOR Clinical Outcome Assessment Emerging Good Practices Task Force
• Voqui (2015) Clinical Outcome Assessment Implementation in Clinical Trials
• Richardson et al (2019) Developing and Implementing Performance Outcome Assessments: Evidentiary, Methodologic, and Operational Considerations