Patient experience data are classified in a variety of ways。Patient experience data may be collected by sponsors or non-sponsors。According to the collection method of PED, it can be divided into pre-designed clinical trials, patient preference studies, natural history studies, interviews, questionnaires, expert consultations, patient communication conference summaries, etc。The data nature of PED includes qualitative, semi-quantitative or quantitative。Primary uses of PED in benefit-risk assessment，Including clinical outcome assessment, COA), which provides patient preference information on benefits and risks，PPI)，And other insights, needs, or priorities about the disease and its treatment，And support adequate benefit-risk assessment。The following describes COA and PPI。

(I) Clinical Outcome Assessment (COA)

clinical outcome assessment, COA) is from the patient and their caregiver, doctor, or other evaluator，An assessment tool or instrument used to evaluate the feelings, functioning, or survival status of an individual patient，Often a subjective assessment process is required rather than direct presentation of facts。COA was evaluated in terms of symptoms,体征, daily function, overall health status, quality of life and satisfaction。

Depending on the reporter，COA is divided into clinician reported outcomes，ClinRO), patient-reported outcome，PRO), observer-reported outcome，ObsRO)，And also includes performance outcomes based on tests to assess patient performance，PerfO)。

PRO is delivered directly by the patientSelf-reported measurements of symptoms, signs, functions, or other aspectsWithout external correction or explanation by a doctor or other person。The tools for measuring PRO are usually scales, questionnaires, numerical scores, or patient logs。例如，patient global assessment, PGA, numeric rating scale, NRS, the 36-item short from health survey, etc。

ClinRO is a medical professional's measurement of a patient's disease and health status based on an examination or observation.症状、Clinical judgments of behavior or other phenomena associated with disease or based on laboratory indicators。Examples include the Glasgow Coma Scale (GCS) and Psoriasis Area and Severity Index (PASI)。

ObsRO is a measure of patient health outcomes reported by caregivers in their daily lives。For example, a diary of the frequency of seizures in children with Dravet syndrome recorded by the caregiver。

PerfO is a measurement that is evaluated by an appropriately trained person or the patient alone when the patient performs a standardized functional task。For example, measures of walking speed (e.g., 6-minute walk test, 6MWT), memory reconstruction tests (e.g., word recall test), or other cognitive tests (e.g., number symbol substitution test)。此外，Composite clinical outcome assessment tools may include multiple types of clinical outcome assessment, such as the combination of ClinRO and PRO。

Clinical endpoints based on COA can be used to evaluate clinical benefit。Clinical benefit is defined as the effect of a treatment or intervention on the individual patient's perception, function, or survivalBeneficial effects can be measured by improvement or delay in deterioration。Clinical outcome assessment endpoints can be used as primary endpoints (single endpoints or compound endpoints) or pre-defined secondary endpoints to evaluate clinical benefit。For example, key clinical trials for idiopathic constipation use an average of 3 or more spontaneous complete bowel movement (SCBM) per week as the primary endpoint;In pivotal clinical trials for myelofibrosis indications，Radiographic findings (reduced spleen volume) were used as the primary endpoint，The Myelofibrosis Symptom Assessment Form (Myelofibrosis Symptom Assessment Form) was collected from patient diaries, Symptom improvement in MFSAF) as a key secondary PRO endpoint。

In addition, safety can be assessed by the COA tool。For example, in clinical trials for non-small cell lung cancer, the Visual Symptom Assessment Questionnaire (VSAQ-ALK) is used to assess the ophthalmic safety of therapeutic agents。

(II) Patient Preference Information (PPI)

Patient preference information refers to the qualitative or quantitative assessment of a patient's willingness to choose and acceptance of different clinical outcomes or other characteristics of a particular treatment。In benefit-risk assessment, PPIs can provide patients' preference for benefits and tolerance for risks。For example, ask the patient about his or her propensity to use drugs with different uses (such as topical, oral, or injectable), or whether he or she is willing to accept potential risks for possible benefits。

In different stages of drug development, PPI may have a certain guiding effect on treatment background, endpoint selection and dynamic benefit-risk assessment。For example, PPI helps with clarityClinical benefit as measured by the trial endpointFor the importance of the patient, understand the patient's balance of benefits and risks for a particular drug, and understand the patient population's views on various treatment optionsSelection preferenceAnd heterogeneity。

The application of PPI in benefit-risk assessment should fully consider the indication background,The application value of patient preference informationPPI collection methods and representativeness of patients' views。The value of patient preference information should be carefully considered in the following cases:The efficacy of the drug is clear but there are serious or uncertain safety risks, and the patient is willing to accept higher risks to obtain the possible benefit;(2) There are significant differences between patients in their views of the most important benefits and/or risks;(3) Patients' views are inconsistent with those of medical professionals。In general, benefit-risk assessments cannot be made solely on the basis of patient preference information for drugs with poor efficacy or serious safety concerns。

(1) Overview of important factors in benefit risk assessment

Patient experience data can provide key considerations for drug benefit-risk assessment。Under the overall framework of drug benefit-risk assessment, patient experience data can be incorporated to improve it, focusing on patient clinical needs and patient perspectives to ensure patient-centered benefit-risk assessment。

The benefit-risk assessment framework and concerns based on patient experience data include the following aspects (see Table 1): "Treatment context analysis" (disease onset, severity and prognosis, characteristics of available therapies, unmet clinical needs, etc.), specific drug "benefits" and "Risks and risk management"。For each of these aspects, the relevant evidence (including data quality and credibility) as well as uncertainties and their potential impact need to be assessed。最后，Combine the severity of the disease with the current unmet clinical needAnd synthesize the evidence and uncertainty about the benefits and risks of the drug, combined with the severity of the disease and the current unmet clinical need, to draw specific conclusions about the benefit risk assessment。

(二) Patient experience data support key considerations in benefit-risk assessment

In benefit-risk assessment, patient experience data can provide useful information for a range of considerations, such as the natural history of the disease,疾病Main symptoms, signs and diseasesThe impact on the patient's life, the patient's experience of treatment or perspective on unmet needs,Patient-reported efficacy or safety outcomes, patient preferences for treatment options or outcome measures, etc. (see Table 1 for details)。According to the purpose of data collection, data type and data quality, the scope and function of PED are different。

1.Treatment background

PED can provide a patient's perspective on the impact of the disease and their existing treatment experience。For example, PED helps to gain a clearer understanding of the impact of the disease on the patient, which signs and symptoms are most concerning to the patient, most troubling, and most affecting the quality of daily life。PED also helps to understand how well currently available treatments meet the medical needs of the patient population, including effectiveness, safety, tolerability, convenience, accessibility, etc。

For the pathogenesis, clinical symptomsAnd/or clinical benefitThe evaluation indicators of diseases are not fully understood, and PED data also provides insight into the natural history of diseases。For example, some rare diseases have low incidence and complex phenotypes,Lack of effective treatment, clinical trial design for drug research and developmentDrug efficacy and safetyPose a great challenge。The patient's experience and perspective can provide an important reference for the evaluation of the occurrence and development of the disease, the severity of the disease, the effectiveness and safety of treatment, and the prognosis。

2.Clinical benefit

Clinical benefit needs to pay attention to the clinical relevance of its effectiveness indicators, whether it meets the needs of patients, whether the degree of benefit is clinically significant, etc. Patient physical examination data can provide patients' views and preferences for the evaluation of clinical benefit。

2.1 Clinical relevance of efficacy outcomes

Descriptions of clinical benefits usually includeEfficacy (e.g. survival, change in important clinical outcomes, reduction of symptoms and signs, improvement in function, improvement in quality of life), strength of effect, and uncertainty，The distribution of therapeutic effect in the population, the duration of therapeutic effect, etc。As for the selection of effectiveness indicators, it is recommended to judge the clinical correlation between the trial endpoint and the measurement indicator, that is, whether it is the clinical indicator that patients care about most or has the greatest impact on patients, or whether the measurement indicator can predict clinical benefit, according to the current cognition of the disease and the obtained patient experience data。

For clinical trials that directly or relatively directly measure clinical benefits (such as reduction in signs and symptoms, improvement in function, improvement in quality of life) as study endpoints,Clinical outcome assessment endpoint can be selected。If this endpoint is used as a primary or key secondary endpoint indicator, it should fully explain the basis for selection, and provide the collection method of COA data, measurement performance (such as reliability, validity), detailed data analysis and result interpretation。

Benefits in addition to clinical benefits (e.g., ease of medication, compliance, etc.)It may also affect patient preferences and should be given appropriate weight in the benefit-risk assessment。

2.2 Clinical significance of benefit

The need to assess whether the extent of clinical benefit is clinically significant is an important consideration in patient-centered benefit-risk assessment。

Based on the minimally clinically important difference in the meaning of the bed, MCID) or minimum important difference, MID) to set a clinically valuable benefit threshold，Represents the smallest improvement that the patient finds valuable。

When determining the MCID，It should be based on patient experience data，At the same time, it can refer to the relevant guidelines, expert consensus and other recognized standards, and communicate with the review agency in a timely manner to reach a consensus。

When a meaningful difference is shown between groups, it does not represent a meaningful clinical benefit for an individual。Can be considered based on MCID/MIDA clinically meaningful intra-patient change threshold is set to judge whether a patient has achieved the treatment goal, and this value can be used as supporting evidence to evaluate the benefit。

2.3. Risk tolerance and acceptance

In the evaluation of drug safety, it is necessary to pay attention to the feelings and experiences of patients. For example, some patients may have some mild adverse reactions during medication, but long-term medication may also have a significant impact on their quality of life。

In determining the risk of a drug, characteristics such as severity, frequency, and reversibility of adverse events should be considered, as well asAfter the patient had an adverse reactionEffects and potential consequences on medication adherence。PED can be a safety outcome itself (i.e., a COa-based safety endpoint), or it can be used as other supporting evidence, such as risk knowledge (e.g.Whether the patient understands each type of risk and the severity of the risk occurrence and its likelihood), clinical importance (which risk patients perceive to have the greatest impact on quality of life), tolerance of adverse events,The acceptability of risk management measures and the burden of risk management measures on patients。

Patient preference data can provide information on patient risk acceptance, that is, the likelihood of clinical benefit,Whether patients are willing to accept predictable and unknown risks。For example, whether the patient is willing to accept a potential risk for the possible benefit;Patients with certain chronic conditions, who have adapted to the disease and its impact on daily life and can stabilize the condition with existing treatments, may expect greater benefits from new treatments, but cannot afford the higher risks。

3.Benefit - Risk assessment

When a drug has a clear clinical benefit, a good safety profile, and no serious safety risks are found, the benefits can be judged to outweigh the risks。

When a drug has a clear clinical benefit but a safety risk, the benefit-risk ratio should be weighed to consider whether the risk can be controlled through reasonable risk management measures。

When the drug presents a potentially serious safety risk (e.g., life-threatening) and/or may have limited benefit,Or when there is uncertainty, benefit-risk assessment can be challenging。In this case, reliable patient experience data, tailored to a specific purpose, will be helpful in assessing the benefit-risk of the drug。

The benefit-risk assessment of the whole population is the overall evaluation of clinical trial participants;Subgroup assessment is an assessment of some subgroups of patients。When there are inconsistencies between the overall benefit-risk assessment and the subgroup assessment, supporting data from both parts need to be carefully weighed and patient perspectives may also be included。For example, if PED can help identify a subgroup of people with a good benefit-risk ratio when the expected risk of a drug exceeds the benefit for the overall indication population, then this population can be used in subsequent research and development studies to demonstrate whether the drug has a favorable benefit-risk ratio in this population。

(三) Drug life cycle considerations

1.Pre-market research and development

The collection and application of patient experience data is an accumulation process。The accumulation of patient experience data during clinical development is used to guide broader benefit-risk assessments that support continued/discontinued drug development decisions。

The patient experience data collected early on is mostly qualitative and can provide information for benefit-risk assessment and drug development decisions, including identifying unmet clinical needs, identifying target patient populations, and identifying key elements of trial design。例如，Patient experience data collected early in clinical development can be analyzed in an open-ended question format or against patient health dataTo understand the natural history of the disease, clinical practice preferences, differences in patient subgroups, etc., to identify unmet patient needs and determine the target patient population。

With the continuous accumulation of PED, the scope of patient experience data was gradually focused and the method was gradually quantified in the later stage。For example, developing a quantitative COA assessment tool to more directly measure the clinical outcomes of most concern to patients and validate the tool's clinical relevance to identify clinically meaningful thresholds of change;Can collect量化Information about patient preferences,To determine a patient's willingness to use a drug, quantify risk acceptance and perform a benefit-risk assessment of the drug based on clinical and patient preference evidence。

This quantitative PED information collected at a later stage can be used as direct evidence or complementary information to clinical efficacy and safety data to support dynamic benefit-risk assessment。When faced with major development decisions need to be discussed with the review body, PED collection and application can also be an important part of the communication with the review body。

2.Post-marketing use phase

During the post-marketing use of the drug, it should be based on the accumulation of new information (including PED),Continuous evaluationThe benefit-risk status of a drug,If new risks are discovered, decide whether to take appropriate regulatory measuresThese include modifying the risk management plan, adding post-market study requirements, changing the prospectus, or withdrawing from the market to maximize patient benefits and minimize risks。Encourage additional PED collection after listing, either by sponsor in response to specific post-listing requests or through voluntary research (such as interviews, questionnaires, studies of patient usage preferences, etc.) initiated by sponsor, investigator, or patient organization。These patient experience data can not only truly communicate to the general population of patients, healthcare professionals and related personnel about the patient's experience and feelings about drug use, but also provide new evidence for dynamic assessment of benefit risk。

When sponsors plan to collect and utilize patient experience data as part of a benefit-risk assessment, early communication with review institutions is encouraged during the design phase of such studies to obtain timely feedback on whether the study design, data collection, and oversight meet the requirements。

Sponsors who plan to use PRO or other COAs as primary or key secondary endpoints for confirmatory studies should communicate with the review body in a timely manner。In addition, in the course of clinical trials, if significant adjustments are made to the clinical trial protocol due to changes in PRO or other COA, timely communication should be made with the review institution。For details, please refer to the "Communication and Communication Measures for Drug Development and Technical Review", "Guidelines for the Application of Patient-Reported Outcomes in Drug clinical Research (Trial)", "Guidelines for Patient-centered clinical Trial Design" and other relevant guidelines。

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