Clinical Outcomes PDF

Clinical outcomes Moetaza Soliman, PhD  Clinical outcomes Clinical outcomes are the end result of any therapeutic interventions applied to patients. They may be: – immediate and short-term such as the effects of vasoactive drugs on the cardiovascular system. – long-term...

Clinical outcomes Moetaza Soliman, PhD  Clinical outcomes Clinical outcomes are the end result of any therapeutic interventions applied to patients. They may be: – immediate and short-term such as the effects of vasoactive drugs on the cardiovascular system. – long-term when the effects of the whole treatment episode on the patient’s well-being are evaluated.  Types of Clinical Outcome Assessments The U.S. Food and Drug Administration (FDA) has provided input on types of clinical outcome assessments: 1. Clinician-reported outcome 2. Patient-reported outcome 3. Observer-reported outcome 4. Performance outcomes  Clinician-reported outcome An assessment that is determined by an observer with some recognized professional training that is relevant to the measurement being made. Some clinical outcomes, such as all-cause mortality, can be ascertained directly and may be more reliable than measures that are subject to interpretation by individual health care providers, such as angina or depression.  Patient-reported outcome A measurement based on a report that comes directly from the patient (i.e., the study subject) about the status of particular aspects of or events related to a patient’s health condition. PROs are recorded without amendment or interpretation of the patient’s response by a clinician or other observer.  Observer-reported outcome An assessment that is determined by an observer who does not have a background of professional training that is relevant to the measurement being made, i.e., a non-clinician observer such as a caregiver. This type of assessment is often used when the patient is unable to self-report (e.g., infants, young children). An ObsRO assessment should only be used in the reporting of observable concepts (e.g., signs); ObsROs cannot be validly used to directly assess symptoms (e.g., pain) or other unobservable concepts.  Performance outcomes These are measurements collected when a patient is asked to complete a well-defined, repeatable, and standardized task, such as reading an eye chart.  Clinician-reported outcomes (ClinRO) Report that comes from a health professional after observation of a patient's health condition. It requires the knowledge and/or judgement of a medical professional to be interpreted and reported. It is a type of clinical outcome assessment and include clinically observable signs, behaviors, and clinical manifestations of the disease.  Types of ClinRO Readings: dichotomous (e.g., yes/no reports) – Presence or absence of a fracture on a radiography. – Presence or absence of skin lesions. – Presence or absence of emetic episodes. Rates: categorical scoring record (from at least 3 categories) – Spleen size. – Change in skin lesions. – Improvement in vein appearance. Clinician global assessments: – Evaluation based on clinicians’ overall judgment of the patient’s total health status.  Examples of categorical ClinRO assessments Unified Parkinson’s Disease Rating Scale. The Aronchick Scale in bowel preparation for colonoscopy. The Brief Psychiatric Rating Scale in mental disorders. Psoriasis Area and Severity Index (PASI) score for psoriasis.  Psoriasis Area and Severity Index (PASI) score for psoriasis. It produces a numeric score ranging from 0 to 72. In general, a PASI score of 5 to 10 is considered moderate disease, and a score over 10 is considered severe. PASI 90 response is defined as 90% improvement or more from baseline on PASI score. PASI 75 response is defined as 75% improvement or more from baseline on PASI score.  In calculating the PASI, severity is determined by dividing the body into four regions: head (h), upper extremities (u), trunk (t) and lower extremities (l), that account for 10%, 20%, 30%, and 40% of the total body surface area (BSA), respectively. Each of these areas is assessed separately for erythema, induration ‫تصلب‬, and scaling, which is rated on a scale of 0 (none) to 4 (very severe).  PASI score for psoriasis patient Head & Upper Trunk Lower neck extremities extremities Erythema 0-4 4 4 4 4 Scale 0-4 4 4 4 4 Induration 0-4 4 4 4 4 Sum 12 12 12 12 Body surface 6 6 6 6 area 0-6 Sum x Area 72 72 72 72 Area 0.1 0.2 0.3 0.4 multiplier Sum x Area 7.2 14.4 21.6 28.2 PASI total 72  The Brief Psychiatric Rating Scale in mental disorders It is a rating scale which a clinician or researcher may use to measure psychiatric symptoms such as depression, anxiety, hallucinations, psychosis and unusual behaviour. The scale is one of the oldest, most widely used scales to measure psychotic symptoms. It should be administered by a clinician who is knowledgeable concerning each of the symptom domains, and severe mental health disorders.  It is particularly useful in gauging the efficacy of treatment in patients who have moderate to severe psychoses. It consists of 18 questions. The rater enters a number for each symptom construct that ranges from 1 (not present) to 7 (extremely severe). 0 = not assessed, 4 = moderate, 1 = not present, 5 = moderately severe, 2 = very mild, 6 = severe, 3 = mild, 7 = extremely severe Patient-reported outcomes (PROs) Patient-reported outcomes (PROs) include any outcomes that are based on data provided by patients or by people who can report on their behalf. A real advantage of PRO assessment is that the data collected for one purpose can be used in multiple different ways including clinical care, quality assessment, quality improvement, research and public reporting.  The FDA defines a PRO as “a measurement based on a report that comes directly from the patient (i.e., 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. PROs refer to patient ratings and reports about any of several outcomes, including – health status, – health-related quality of life, – quality of life defined more broadly, symptoms, – functioning, – satisfaction with care, and – satisfaction with treatment.  PRO measures may be designed to measure the current state of health of an individual or to measure a change in health state. To be most useful, it is important to have evidence about the reliability, validity, responsiveness, and interpretation of PRO measures. Both patient-reported outcomes and health- related quality of life are considered Humanistic outcomes.  Reasons to Measure PROs They are used increasingly to help determine whether treatments are doing more good than harm. These outcomes are assessed and often compared to clinical measurements that remain the primary end- points for most clinical trials and for many clinicians, because they are familiar through long or repeated use. Epidemiological investigations and population surveys incorporate self-reported outcomes to compare populations and to describe the status of different populations.  Some questions cannot be answered without asking the patient Reduction in pain (hip replacement) Improved functioning (cataract extraction) Patient best observer of some events and health outcomes (complications)  Why should we use PROs in clinical trials? Changes in the therapeutic targets in the growing context of chronic diseases and palliative treatment in a rising old population Nowadays, therapeutic benefits are rarely curative, or prolonging survival, but improving symptoms and functional status. Availability of PRO questionnaires correctly validated and translated for many diseases / conditions  Clinicians underestimate pain severity (Irritable Bowel Syndrome - IBS) Patients 39.0 ± 24.9 (n=232) GPs 30.4 ± 21.0 (n=307) Difference 8.6 (28%) Correlation = 0.31 (n=232)  PROM is Not It is not a laboratory or performance measure It does not measure all clinically relevant patient reported outcomes It is not adequate alone to use for most screening or diagnostic needs  Composite outcome It consists of more than one outcome together. It can cover many aspects of the disease. It can better describe and evaluate the disease. It can contain more then one type of outcome measures. E.g., Disease activity score 28 joints (DAS28) for rheumatoid arthritis.  Disease activity score 28 joints (DAS28) for rheumatoid arthritis It is a composite measure that consists of: – 28 tender joint count (TJC28). – 28 swollen joint count (SJC28). – Patient global health assessment (0-100) (GH). – C-reactive protein (CRP) or erythrocytes sedimentation rate (ESR). DAS28-CRP = 0.56* √(TJC28) + 0.28* √(SJC28) + 0.36*ln (CRP + 1) +0.014*(GH) + 0.96. DAS28-ESR = 0.56* √(TJC28) + 0.28* √(SJC28) + ( 0.7 * ln (ESR)) + (0.014 * GH). Outcome Measurement Properties Reliability Validity Variability Responsiveness Minimum Detectable Change Minimum Clinically Important Difference  Reliability: Are measures consistent? – Degree to which a score or other measure remains unchanged upon test and retest, across different interviewers or assessors , or across items on the same test Validity: Does it measure what it’s supposed to measure? – Degree to which a measure assesses what it is intended to measure Variability: – Distribution of values associated with an outcome measure in the population of interest, where a broader range of values shows more variability  Minimum Detectable Change: Has real change occurred? Minimum Clinically Important Difference – Smallest change that is important to patients Responsiveness: Sensitivity to Change – Ability of a measure to detect change in an individual or group over time – Floor and Ceiling Effects  Ceiling Effect Limitation of a measure in which the instrument does not register a further increase in score for the highest scoring individual Ceiling: When the task is too easy, and all patients perform at or near perfect, you have a ceiling effect  Floor Effect Limitation of a measure in which the instrument does not register a further decrease in score for the lowest scoring individual Floor; When the task is too hard and everyone performs at the worst possible level. Thank you