Updated application with optimizations

curated_qa_pairs.json

@@ -1,22 +1,595 @@
 [
     {
-        "question": "What is Adagrasib (Krazati®) used for?",
-        "answer": "Adagrasib (Krazati®) is used for the treatment of adult patients with advanced non-small cell lung cancer (NSCLC) with KRAS G12C mutation and disease progression after at least one prior systemic therapy."
+      "question": "What is Adagrasib (Krazati®) used for?",
+      "answer": "Adagrasib (Krazati®) is used for the treatment of adult patients with advanced non-small cell lung cancer (NSCLC) with KRAS G12C mutation and disease progression after at least one prior systemic therapy."
     },
     {
-        "question": "What are the comparator treatments for Adagrasib in the PICO exercises?",
-        "answer": "In PICOs 1 and 2, the comparator treatments are Sotorasib monotherapy and platinum-based doublet chemotherapy. In PICO 3, the comparator treatment is Docetaxel monotherapy. In PICO 4, the comparator treatment is immune checkpoint inhibitor monotherapy."
+      "question": "What are the comparator treatments for Adagrasib in the PICO exercises?",
+      "answer": "In PICOs 1 and 2, the comparator treatments are Sotorasib monotherapy and platinum-based doublet chemotherapy. In PICO 3, the comparator treatment is Docetaxel monotherapy. In PICO 4, the comparator treatment is immune checkpoint inhibitor monotherapy."
     },
     {
-        "question": "What are the effectiveness measures used in the PICO framework?",
-        "answer": "Effectiveness measures in the PICO framework typically include outcomes such as overall response rate, progression-free survival, and overall survival. In these PICOs, Adagrasib is used as monotherapy in PICOs 1 and 2, and as monotherapy or in combination with platinum-based chemotherapy in PICO 3, while in PICO 4 it may be used as monotherapy or in combination therapy."
+      "question": "What are the effectiveness measures used in the PICO framework?",
+      "answer": "Effectiveness measures in the PICO framework typically include outcomes such as overall response rate, progression-free survival, and overall survival. In these PICOs, Adagrasib is used as monotherapy in PICOs 1 and 2, and as monotherapy or in combination with platinum-based chemotherapy in PICO 3, while in PICO 4 it may be used as monotherapy or in combination therapy."
     },
     {
-        "question": "What adverse events were monitored in the PICO studies?",
-        "answer": "The adverse events monitored in the PICO studies include a range of treatment-related side effects. The provided context does not detail them fully; more detailed study data would be needed for a complete list."
+      "question": "What adverse events were monitored in the PICO studies?",
+      "answer": "The adverse events monitored in the PICO studies include a range of treatment-related side effects. The provided context does not detail them fully; more detailed study data would be needed for a complete list."
     },
     {
-        "question": "How does Adagrasib compare to immune checkpoint inhibitors?",
-        "answer": "The analysis suggests that comparisons between Adagrasib and immune checkpoint inhibitors (or Docetaxel) should account for patients' prior treatment lines. Direct comparisons may not be relevant in certain subgroups, especially in patients with only one prior line of systemic therapy."
+      "question": "How does Adagrasib compare to immune checkpoint inhibitors?",
+      "answer": "The analysis suggests that comparisons between Adagrasib and immune checkpoint inhibitors (or Docetaxel) should account for patients’ prior treatment lines. Direct comparisons may not be relevant in certain subgroups, especially in patients with only one prior line of systemic therapy."
+    },
+    {
+      "question": "Why were the PICO exercises carried out by the JCA subgroup in Spring 2024?",
+      "answer": "They were conducted to test and improve the content of the Guidance on the scoping process by applying it to real cases, ensuring that the resulting guidance would be practical and refined for future assessments."
+    },
+    {
+      "question": "How many PICO exercises were carried out in total for testing the guidance?",
+      "answer": "A total of six PICO exercises were conducted: three for Medicinal Products (MPs) and three for Medical Devices (MDs)."
+    },
+    {
+      "question": "What does ‘JCA subgroup’ refer to in the context of these PICO exercises?",
+      "answer": "The ‘JCA subgroup’ refers to a group involved in Joint Clinical Assessments, which oversaw and performed the test exercises to refine the scoping guidance."
+    },
+    {
+      "question": "Which medicinal product is addressed by PICO exercise MP 03?",
+      "answer": "PICO exercise MP 03 focuses on the medicinal product Adagrasib (Krazati®)."
+    },
+    {
+      "question": "What is the primary indication for Adagrasib according to the PICO exercise MP 03?",
+      "answer": "The primary indication is for adult patients with advanced NSCLC carrying a KRAS G12C mutation who have disease progression after at least one prior systemic therapy."
+    },
+    {
+      "question": "How many PICOs were defined under the PICO exercise MP 03?",
+      "answer": "Thirteen PICOs (PICO 1 to PICO 13) were defined in the document for MP 03 concerning Adagrasib."
+    },
+    {
+      "question": "What is the main intervention in all PICOs described for MP 03?",
+      "answer": "The main intervention in every PICO for MP 03 is Adagrasib (Krazati®) monotherapy."
+    },
+    {
+      "question": "In PICO 1, what is the comparator to Adagrasib monotherapy?",
+      "answer": "In PICO 1, the comparator is Sotorasib monotherapy."
+    },
+    {
+      "question": "Which patient population does PICO 1 focus on?",
+      "answer": "PICO 1 focuses on adult patients with advanced NSCLC carrying the KRAS G12C mutation who have progressed after at least one prior line of systemic therapy."
+    },
+    {
+      "question": "In PICO 2, what is the chosen comparator for Adagrasib?",
+      "answer": "PICO 2 compares Adagrasib monotherapy to platinum-based doublet chemotherapy."
+    },
+    {
+      "question": "Which comparator is explored in PICO 3?",
+      "answer": "PICO 3 compares Adagrasib monotherapy with Docetaxel monotherapy."
+    },
+    {
+      "question": "What additional information is requested in PICO 1 and 3 regarding prior lines of therapy?",
+      "answer": "They request subgroup analyses where patients are stratified into two groups: one with 1 prior line of systemic therapy for advanced disease, and the other with 2 or more lines of prior therapy."
+    },
+    {
+      "question": "Which comparator is presented in PICO 4?",
+      "answer": "PICO 4 compares Adagrasib monotherapy to immune checkpoint inhibitor monotherapy."
+    },
+    {
+      "question": "What is the rationale behind requesting subgroup analyses in some PICOs?",
+      "answer": "Subgroup analyses help determine how Adagrasib performs in patients with different numbers of prior treatments, clarifying its effectiveness across varying treatment histories."
+    },
+    {
+      "question": "What combination of comparators is included in PICO 5?",
+      "answer": "PICO 5 allows multiple comparators: platinum-based doublet chemotherapy, single-agent chemotherapy, or immune checkpoint inhibitor monotherapy."
+    },
+    {
+      "question": "In PICO 6, which subpopulation is specifically targeted?",
+      "answer": "PICO 6 targets adult patients with advanced NSCLC carrying KRAS G12C who have progressed after first-line treatment with an immune checkpoint inhibitor monotherapy and have not received prior platinum-based doublet chemotherapy."
+    },
+    {
+      "question": "What is the comparator in PICO 6?",
+      "answer": "The comparator in PICO 6 is platinum-based doublet chemotherapy."
+    },
+    {
+      "question": "How are patients stratified in PICO 6?",
+      "answer": "Patients are stratified into three groups: those with 1 prior line of therapy, those with 2 or more lines of therapy, and (implicitly) those meeting the criteria of prior immune checkpoint inhibitor but no prior platinum-based chemotherapy."
+    },
+    {
+      "question": "Which subpopulation does PICO 7 address?",
+      "answer": "PICO 7 addresses adult patients with advanced NSCLC carrying KRAS G12C who have progressed after treatment with an immune checkpoint inhibitor and platinum-based doublet chemotherapy, either sequentially or in combination."
+    },
+    {
+      "question": "What comparator is used in PICO 7?",
+      "answer": "In PICO 7, the comparator is Docetaxel monotherapy."
+    },
+    {
+      "question": "How does PICO 7 propose stratifying patients?",
+      "answer": "It proposes stratifying into three groups: (a) 1 prior line of therapy, (b) 1 prior line of therapy consisting of platinum-based chemotherapy plus an immune checkpoint inhibitor, and (c) 2 or more prior lines of therapy."
+    },
+    {
+      "question": "What is unique about the patient population in PICO 8?",
+      "answer": "PICO 8 focuses on adult patients with advanced NSCLC carrying KRAS G12C who have progressed after first-line platinum-based doublet chemotherapy plus an immune checkpoint inhibitor."
+    },
+    {
+      "question": "Which two treatments are compared in PICO 8?",
+      "answer": "PICO 8 compares Adagrasib monotherapy with Sotorasib monotherapy."
+    },
+    {
+      "question": "Why might PICO 8 be of particular interest?",
+      "answer": "PICO 8 directly compares Adagrasib to another KRAS G12C inhibitor (Sotorasib), which is especially relevant for patients who have progressed after combination chemotherapy and immunotherapy."
+    },
+    {
+      "question": "What additional therapy is considered as a comparator in PICO 9 alongside Docetaxel?",
+      "answer": "PICO 9 considers Docetaxel plus Nintedanib as the comparator for patients with advanced NSCLC (adenocarcinoma histology) carrying KRAS G12C."
+    },
+    {
+      "question": "Which histology type is highlighted in PICO 9?",
+      "answer": "PICO 9 highlights patients with adenocarcinoma histology in advanced NSCLC carrying the KRAS G12C mutation."
+    },
+    {
+      "question": "For which subpopulation is PICO 10 intended?",
+      "answer": "PICO 10 is for adult patients with advanced non-squamous NSCLC carrying KRAS G12C who have progressed after at least one prior line of therapy and have not been previously treated with pemetrexed."
+    },
+    {
+      "question": "What is the comparator in PICO 10?",
+      "answer": "In PICO 10, the comparator is pemetrexed monotherapy."
+    },
+    {
+      "question": "Which outcomes are consistently evaluated across all these PICOs?",
+      "answer": "Common outcomes include overall survival (OS), progression-free survival (PFS), quality of life (QoL), objective response rate (ORR), time-to-response, progression on subsequent treatment (PFS2), and progression of brain metastases."
+    },
+    {
+      "question": "Which quality of life questionnaires are preferred in the PICO outcomes list?",
+      "answer": "The preferred QoL questionnaires are EORTC QLQ-C30/LC-13, EQ-5D, and SF-36."
+    },
+    {
+      "question": "What is QLQ-LC13 used for?",
+      "answer": "QLQ-LC13 is a lung cancer–specific module used alongside QLQ-C30 to assess quality of life aspects specific to lung cancer patients."
+    },
+    {
+      "question": "Which measure is used to evaluate symptom changes in QoL questionnaires according to the outcomes list?",
+      "answer": "Responder analyses defining a 15% reduction in symptom scores can be used to evaluate changes in quality of life."
+    },
+    {
+      "question": "What does ORR stand for in the context of these outcomes?",
+      "answer": "ORR stands for Objective Response Rate, indicating the proportion of patients whose cancer shrinks or disappears after treatment."
+    },
+    {
+      "question": "How is time to progression of brain metastases relevant in these PICOs?",
+      "answer": "Time to progression of brain metastases is critical for understanding how well a therapy controls intracranial disease, which can significantly impact morbidity in advanced NSCLC."
+    },
+    {
+      "question": "What safety outcomes are mentioned in the guidance?",
+      "answer": "Safety outcomes include adverse events (AEs), serious and severe AEs, death related to AEs, treatment discontinuation due to AEs, treatment interruption due to AEs, and dose reductions due to AEs."
+    },
+    {
+      "question": "Why does the guidance emphasize severity grading for adverse events?",
+      "answer": "Severity grading (e.g., Common Terminology Criteria for Adverse Events Grades 3-5) helps standardize reporting and allows clearer comparisons across treatments."
+    },
+    {
+      "question": "What kind of analyses are used to assess quality of life over time?",
+      "answer": "Analyses such as change from baseline to a specified week and time-to-deterioration (TTD) for QoL measures are employed."
+    },
+    {
+      "question": "Why are subgroup analyses important in these PICOs?",
+      "answer": "Subgroup analyses help determine whether Adagrasib’s efficacy and safety vary based on the number of prior treatments, type of prior therapy, or specific histology subtypes."
+    },
+    {
+      "question": "What is the primary condition targeted by Adagrasib in these exercises?",
+      "answer": "The primary condition is advanced non-small cell lung cancer (NSCLC) with the KRAS G12C mutation."
+    },
+    {
+      "question": "Which therapy lines must a patient typically have undergone before receiving Adagrasib according to these PICOs?",
+      "answer": "Most PICOs focus on patients who have progressed after at least one prior line of therapy, with some specifying prior immune checkpoint inhibitor or platinum-based chemotherapy."
+    },
+    {
+      "question": "In PICO 11, what are some of the comparator options beyond standard chemotherapy?",
+      "answer": "PICO 11 includes various comparators such as Pemetrexed, Nivolumab, Pembrolizumab, Atezolizumab, and Docetaxel (with or without nintedanib), depending on PD-L1 status and tumour histology."
+    },
+    {
+      "question": "Why does PICO 11 specify PD-L1 status?",
+      "answer": "PD-L1 status determines the appropriateness of treatments like Pembrolizumab, which may only be recommended for patients with PD-L1-expressing tumours (TPS ≥ 1%)."
+    },
+    {
+      "question": "In PICO 12, what different platinum-based regimens might be used as comparators?",
+      "answer": "Cisplatin or Carboplatin in combination with third-generation cytostatics (e.g., vinorelbine, gemcitabine, docetaxel, paclitaxel, pemetrexed) or monotherapy with gemcitabine/vinorelbine (for ECOG 2) are potential comparators."
+    },
+    {
+      "question": "Why might monotherapy with gemcitabine or vinorelbine be considered in PICO 12?",
+      "answer": "Monotherapy is considered for patients with ECOG performance status 2 who may not tolerate platinum-based combination treatments."
+    },
+    {
+      "question": "In PICO 13, which comparators besides Docetaxel are identified?",
+      "answer": "Comparators in PICO 13 include docetaxel plus nintedanib (for adenocarcinoma), docetaxel plus ramucirumab, pemetrexed (for non-squamous histology), vinorelbine, or sotorasib."
+    },
+    {
+      "question": "What is the significance of docetaxel plus ramucirumab in PICO 13?",
+      "answer": "Docetaxel plus ramucirumab is another second-line option sometimes used in advanced NSCLC, making it a relevant comparator for Adagrasib in that subpopulation."
+    },
+    {
+      "question": "Why is sotorasib included as a comparator in PICO 13?",
+      "answer": "Sotorasib, like Adagrasib, targets KRAS G12C, making it an important head-to-head comparator for patients who have progressed after first-line or sequential immunotherapy plus chemotherapy."
+    },
+    {
+      "question": "What overarching lessons were learned from these PICO exercises?",
+      "answer": "Each round of exercises provided insights into refining the scoping process and clarifying how final guidance should be structured, ensuring comprehensive and relevant PICOs for future assessments."
+    },
+    {
+      "question": "Why is there no complete standardization among the PICO exercises?",
+      "answer": "Because the exercises were iterative, lessons learned from each round were used to improve the guidance for the next, resulting in variations across exercises."
+    },
+    {
+      "question": "What is the relevance of the final version of the guidance in relation to these exercises?",
+      "answer": "The final version of the guidance was drawn up after all exercises, incorporating the experience gained. Therefore, the exercises do not fully reflect the final guidance."
+    },
+    {
+      "question": "Do these PICO exercises affect national assessments or evaluations of MPs or MDs?",
+      "answer": "No. The final PICOs have no impact or consequences on national assessments or evaluations; they were for testing and refining the guidance only."
+    },
+    {
+      "question": "Why is Adagrasib an important focus for PICO 1 to PICO 13?",
+      "answer": "Adagrasib targets a specific KRAS G12C mutation in advanced NSCLC, an area of high unmet need, making it a critical candidate for detailed PICO evaluations."
+    },
+    {
+      "question": "What is the purpose of measuring PFS2 in these PICOs?",
+      "answer": "PFS2 (time to progression on the subsequent treatment line) provides insight into how Adagrasib impacts not just the immediate line of therapy but also subsequent disease progression."
+    },
+    {
+      "question": "How does the guidance suggest handling brain metastases progression data?",
+      "answer": "It recommends tracking the time to progression of brain metastases as a specific outcome to assess the drug’s intracranial control."
+    },
+    {
+      "question": "Why might immune checkpoint inhibitors be used as comparators in several PICOs?",
+      "answer": "Immune checkpoint inhibitors are standard-of-care options for advanced NSCLC, making them key comparators for a new targeted agent like Adagrasib."
+    },
+    {
+      "question": "What factor determines whether single-agent chemotherapy is used as a comparator in the PICOs?",
+      "answer": "Patient characteristics, such as prior therapy lines, tolerance, and performance status, can justify using single-agent chemotherapy (e.g., docetaxel) versus combination therapies."
+    },
+    {
+      "question": "How do PICOs ensure that relevant comparators are considered for different lines of therapy?",
+      "answer": "By specifying separate subpopulations and prior treatments, each PICO tailors comparator choices (e.g., docetaxel, platinum doublets, immunotherapies) to match the patient’s treatment history."
+    },
+    {
+      "question": "What type of lung cancer is the primary focus of these PICO exercises?",
+      "answer": "All the exercises focus on advanced NSCLC, specifically with the KRAS G12C mutation."
+    },
+    {
+      "question": "Are there any PICOs addressing metastatic brain lesions in isolation?",
+      "answer": "No specific PICO addresses only brain metastases, but time to progression of brain metastases is included as an outcome measure across the PICOs."
+    },
+    {
+      "question": "What does the term “Full population” mean in certain PICOs?",
+      "answer": "“Full population” indicates that the PICO applies to all adult advanced NSCLC patients with KRAS G12C mutation who meet the prior treatment criteria, without further histological or PD-L1 restrictions."
+    },
+    {
+      "question": "Why does PICO 9 focus on adenocarcinoma histology?",
+      "answer": "Docetaxel plus nintedanib is specifically indicated for advanced adenocarcinoma NSCLC, making histology an important criterion in PICO 9."
+    },
+    {
+      "question": "What is the role of PD-L1 expression in deciding comparators for some PICOs?",
+      "answer": "PD-L1 expression can guide the use of certain immunotherapies like Pembrolizumab, making it a relevant factor in comparator selection where immunotherapy is considered."
+    },
+    {
+      "question": "Do the PICO exercises include cost-effectiveness analyses?",
+      "answer": "No mention of cost-effectiveness is made in the PICO documents. The focus is on clinical effectiveness and safety outcomes."
+    },
+    {
+      "question": "Why are certain combinations, like Docetaxel plus Nintedanib or Docetaxel plus Ramucirumab, included in later PICOs?",
+      "answer": "These combinations are recognized second- or later-line options in advanced NSCLC, reflecting real-world comparator choices for Adagrasib."
+    },
+    {
+      "question": "What is the significance of specifying ‘adult’ patients in these PICOs?",
+      "answer": "It clarifies the patient population, as pediatric NSCLC cases are extremely rare and not within the scope of these clinical assessments."
+    },
+    {
+      "question": "Which PICO specifically addresses using Adagrasib after immune checkpoint inhibitor monotherapy without prior platinum-based chemotherapy?",
+      "answer": "That scenario is covered by PICO 6."
+    },
+    {
+      "question": "In which PICO is the question of using Adagrasib after both immune checkpoint inhibitor and platinum-based chemotherapy (sequentially or in combination) explored?",
+      "answer": "That scenario is addressed by PICO 7."
+    },
+    {
+      "question": "Which PICO compares Adagrasib with Sotorasib for a population that has already received both platinum-based chemotherapy and immune checkpoint inhibitor as first-line?",
+      "answer": "PICO 8 makes this comparison."
+    },
+    {
+      "question": "What consideration does PICO 10 bring regarding pemetrexed therapy?",
+      "answer": "PICO 10 specifically addresses patients who have not previously been treated with pemetrexed, making pemetrexed monotherapy a relevant comparator."
+    },
+    {
+      "question": "How do these PICOs address patients with squamous versus non-squamous histology?",
+      "answer": "Some PICOs (e.g., PICO 9, 10, and 11) tailor comparator regimens depending on histology subtype, reflecting real-world clinical guidelines."
+    },
+    {
+      "question": "Which PICO includes the widest range of potential comparators?",
+      "answer": "PICO 5 includes platinum doublet chemotherapy, single-agent chemotherapy, or immune checkpoint inhibitor monotherapy as options."
+    },
+    {
+      "question": "What are the ‘two or more lines of previous systemic therapy’ typically referring to?",
+      "answer": "It indicates patients have received multiple prior regimens for advanced disease, making them a distinct subgroup with potentially more treatment-resistance or toxicity considerations."
+    },
+    {
+      "question": "How do the exercises handle the concept of treatment interruption due to AEs?",
+      "answer": "Treatment interruption due to AEs is reported as one of the safety endpoints, reflecting tolerability and patient adherence."
+    },
+    {
+      "question": "Does the guidance specify a preferred method for measuring overall survival?",
+      "answer": "The guidance does not detail a specific method; OS is generally measured from randomization or treatment start until death from any cause."
+    },
+    {
+      "question": "Why might ‘time-to-deterioration (TTD)’ in QoL be important?",
+      "answer": "TTD measures how quickly patients experience a clinically meaningful drop in QoL, offering a sensitive measure of treatment impact beyond survival metrics."
+    },
+    {
+      "question": "What is the significance of ‘responder analyses’ in QoL assessments?",
+      "answer": "Responder analyses define a threshold (e.g., 15% improvement or reduction in symptoms) to identify the proportion of patients experiencing a clinically meaningful change."
+    },
+    {
+      "question": "Do any of the PICOs explicitly require real-world data?",
+      "answer": "No PICO explicitly states a need for real-world evidence; they focus on clinical trial–like scenarios with defined comparators."
+    },
+    {
+      "question": "Who will use the final PICOs developed from these exercises?",
+      "answer": "Regulatory and health technology assessment bodies could use the final PICOs to guide joint clinical assessments and scoping processes for new treatments."
+    },
+    {
+      "question": "What was the timing of the three rounds of PICO exercises?",
+      "answer": "They were performed sequentially in the Spring of 2024, allowing lessons from each round to inform improvements for the subsequent rounds."
+    },
+    {
+      "question": "What disclaimer is given about these PICO exercises not reflecting the final guidance exactly?",
+      "answer": "Because the exercises were iterative and preceded the final version, there may be discrepancies between the published exercises and the fully refined guidance."
+    },
+    {
+      "question": "Why was it important that the products used in the exercises had already received a positive CHMP opinion or expert panel opinion?",
+      "answer": "This ensured the products had sufficient clinical data for a realistic test of the scoping guidance, making the exercises meaningful and representative."
+    },
+    {
+      "question": "How did the exercises handle ongoing changes to the draft guidance?",
+      "answer": "After each exercise, lessons learned were incorporated into the guidance, meaning the approach evolved during the process."
+    },
+    {
+      "question": "What is the primary goal of these PICO exercises with respect to the scoping process?",
+      "answer": "Their primary goal is to refine how to structure PICOs so that future Joint Clinical Assessments are more thorough, standardized, and efficient."
+    },
+    {
+      "question": "Are the PICO exercises considered formal clinical studies?",
+      "answer": "No, they are exercises for guidance testing. They do not function as formal regulatory or clinical trials."
+    },
+    {
+      "question": "Why is there a focus on KRAS G12C mutation in these PICO exercises for Adagrasib?",
+      "answer": "KRAS G12C is a common driver mutation in NSCLC, and targeted therapies like Adagrasib represent a significant advance in treatment options."
+    },
+    {
+      "question": "Which PICO addresses docetaxel plus nintedanib for adenocarcinoma patients specifically?",
+      "answer": "PICO 9 addresses that comparator combination for patients with an adenocarcinoma histology."
+    },
+    {
+      "question": "Are there any references to real-world practice regarding docetaxel plus ramucirumab?",
+      "answer": "Though widely recognized in some clinical settings, the document only mentions it as a comparator in PICO 13, without further real-world practice discussion."
+    },
+    {
+      "question": "Why is performance status (like ECOG PS 2) relevant in selecting comparators such as gemcitabine or vinorelbine monotherapy?",
+      "answer": "Patients with poorer performance status may not tolerate combination regimens, so single-agent options are more appropriate in those cases."
+    },
+    {
+      "question": "What role does the EORTC QLQ-C30 play in these studies?",
+      "answer": "EORTC QLQ-C30 is a core questionnaire measuring generic cancer-related quality of life, often supplemented by lung cancer–specific modules like QLQ-LC13."
+    },
+    {
+      "question": "Does the document provide any data on the actual efficacy of Adagrasib?",
+      "answer": "No specific data results are provided; the document only outlines how to compare and measure outcomes, not the outcomes themselves."
+    },
+    {
+      "question": "Why might sotorasib be repeatedly chosen as a comparator in some PICOs?",
+      "answer": "Sotorasib is another KRAS G12C inhibitor, making it clinically relevant to compare two targeted agents that address the same mutation."
+    },
+    {
+      "question": "Why does PICO 11 have multiple comparators like nivolumab, pembrolizumab, or atezolizumab?",
+      "answer": "Because the subpopulation might have varied treatment paths, including immunotherapy options based on PD-L1 status and histology."
+    },
+    {
+      "question": "How is 'treatment discontinuation due to AEs' a meaningful endpoint?",
+      "answer": "It indicates if toxicity is severe enough to stop therapy, which directly affects patient safety and treatment feasibility."
+    },
+    {
+      "question": "What is the final stance of the document regarding the PICO exercises’ impact on real clinical decisions?",
+      "answer": "They clarify that these exercises are purely exploratory for refining guidance and do not directly influence clinical practice or national evaluations."
+    },
+    {
+      "question": "What is the typical role of platinum-based doublet chemotherapy in advanced NSCLC?",
+      "answer": "Platinum-based regimens (e.g., cisplatin or carboplatin with another agent) are a common first-line or second-line standard treatment in advanced NSCLC."
+    },
+    {
+      "question": "Which line of therapy is the focus of most PICOs for Adagrasib?",
+      "answer": "Most PICOs focus on Adagrasib after failure of at least one prior line, though some specify second- or later-line settings after immunotherapy or platinum-based chemotherapy."
+    },
+    {
+      "question": "How do the PICOs address the possibility of prior concurrent chemo and immunotherapy?",
+      "answer": "Certain PICOs (like PICO 7, 8, and 13) specifically mention prior sequential or combination therapy with chemotherapy and immune checkpoint inhibitors."
+    },
+    {
+      "question": "What does the guidance say about using Sotorasib after Adagrasib or vice versa?",
+      "answer": "It does not specifically address sequential use of both KRAS G12C inhibitors; it only sets them as comparators in certain subpopulations."
+    },
+    {
+      "question": "Which PICO specifically includes docetaxel in combination with ramucirumab as a comparator?",
+      "answer": "PICO 13 includes docetaxel plus ramucirumab as one of the potential comparators."
+    },
+    {
+      "question": "How does the guidance recommend handling dose reductions?",
+      "answer": "Dose reductions due to AEs should be captured as part of the safety profile, indicating how manageable treatment-related toxicity is."
+    },
+    {
+      "question": "Are immune-related adverse events a separate category in these PICO outcomes?",
+      "answer": "The guidance references safety outcomes generally, without specifying immune-related AEs separately. They would be included under overall AEs if relevant."
+    },
+    {
+      "question": "What is the main purpose of performing three rounds of exercises for MPs and MDs in parallel?",
+      "answer": "The parallel approach aims to collect diverse feedback on the scoping process to refine the guidance effectively, ensuring consistency across different health technologies."
+    },
+    {
+      "question": "Do the PICO exercises differentiate outcomes by PD-L1 expression level besides PICO 11?",
+      "answer": "While PD-L1 expression is highlighted in PICO 11, other PICOs primarily focus on lines of therapy rather than PD-L1 expression."
+    },
+    {
+      "question": "Why is 'time to response' included in the outcomes list?",
+      "answer": "Time to response indicates how quickly patients experience clinical benefit from a therapy, which can be important in aggressive diseases like advanced NSCLC."
+    },
+    {
+      "question": "What is the significance of measuring progression-free survival (PFS)?",
+      "answer": "PFS shows how long patients remain free from disease progression under treatment, reflecting short-term efficacy of the therapy."
+    },
+    {
+      "question": "What is the difference between PFS and PFS2 as stated in these exercises?",
+      "answer": "PFS pertains to time on the current treatment, while PFS2 tracks the time to progression on the subsequent line, offering a broader look at overall disease control."
+    },
+    {
+      "question": "Do any PICOs recommend combining Adagrasib with immunotherapy?",
+      "answer": "All listed PICOs describe Adagrasib monotherapy as the intervention; none explicitly recommends combining it with immunotherapy within these exercises."
+    },
+    {
+      "question": "Which PICO might be most relevant for patients who have never received chemotherapy but did receive an immune checkpoint inhibitor first?",
+      "answer": "PICO 6 is the most relevant for those who received an immune checkpoint inhibitor monotherapy first but not platinum-based doublet chemotherapy."
+    },
+    {
+      "question": "Why might docetaxel appear multiple times as a comparator?",
+      "answer": "Docetaxel is a standard second- or third-line option for advanced NSCLC, making it a frequent comparator for a novel agent like Adagrasib."
+    },
+    {
+      "question": "Which PICO extends the comparator list to single-agent chemotherapy when relevant?",
+      "answer": "PICO 5 specifically includes single-agent chemotherapy, in addition to platinum-based doublet chemotherapy or immune checkpoint inhibitors."
+    },
+    {
+      "question": "Are there any PICOs focusing on patients previously treated with docetaxel?",
+      "answer": "No PICO explicitly states prior docetaxel use as a requirement; docetaxel is generally positioned as a comparator or alternative for subsequent lines."
+    },
+    {
+      "question": "What is the difference between ‘immune checkpoint inhibitor monotherapy’ and ‘immune checkpoint inhibitor plus chemotherapy’ in these exercises?",
+      "answer": "Monotherapy refers to receiving an immune checkpoint inhibitor alone, while combination therapy involves receiving it alongside a platinum-based or other cytotoxic chemotherapy regimen."
+    },
+    {
+      "question": "Why might PICO 1 request a subgroup analysis based on one versus two or more prior lines of therapy?",
+      "answer": "Treatment outcomes and tolerability can differ between patients who are less heavily pretreated versus those who have undergone multiple regimens."
+    },
+    {
+      "question": "Does the document mention any specific real-world data regarding the tolerability of Adagrasib?",
+      "answer": "No, the document outlines how tolerability should be assessed via safety endpoints, but does not present real-world tolerability data."
+    },
+    {
+      "question": "Why might ‘death related to AEs’ be categorized separately from overall survival?",
+      "answer": "It distinguishes deaths directly caused by toxicity from those caused by disease progression, clarifying the safety profile of the therapy."
+    },
+    {
+      "question": "Do the PICOs mention any biomarker testing aside from KRAS G12C and PD-L1?",
+      "answer": "No additional biomarkers are highlighted; the focus remains on KRAS G12C mutation status and PD-L1 expression in some subpopulations."
+    },
+    {
+      "question": "Which PICO includes the possibility of docetaxel in combination with nintedanib specifically for patients with PD-L1–negative tumours and adenocarcinoma histology?",
+      "answer": "PICO 11 mentions that docetaxel plus nintedanib is suitable only for patients with PD-L1–negative tumours and adenocarcinoma histology."
+    },
+    {
+      "question": "What is the overall message regarding these PICO exercises published in the document?",
+      "answer": "They are shared for transparency to show how scoping guidance was tested and refined, but they are not binding on future decisions or final guidance."
+    },
+    {
+      "question": "How does the final endorsed version of the guidance relate to the PICO exercises?",
+      "answer": "The final endorsed version was developed after these exercises concluded and integrated all feedback and lessons learned from the iterative process."
+    },
+    {
+      "question": "Do any of these PICOs recommend a specific schedule or dosage for Adagrasib?",
+      "answer": "No dosage or schedule details are included; the exercises only state Adagrasib monotherapy as the intervention to be compared."
+    },
+    {
+      "question": "Was the scoping process for medical devices also tested alongside medicinal products?",
+      "answer": "Yes, three exercises for medical devices were conducted in parallel, but the provided text focuses on the medicinal product exercises."
+    },
+    {
+      "question": "Which PICO might be most relevant for patients whose tumours express PD-L1 at a high level (≥ 1%)?",
+      "answer": "PICO 11 includes pembrolizumab as a comparator for patients with PD-L1–expressing tumours, making it relevant for that subset."
+    },
+    {
+      "question": "Why is combination therapy with carboplatin and nab-paclitaxel listed as a comparator in PICO 12?",
+      "answer": "Carboplatin plus nab-paclitaxel is a recognized first-line or subsequent-line regimen for advanced NSCLC, making it an appropriate comparator."
+    },
+    {
+      "question": "What justifies using single-agent docetaxel in PICO 3?",
+      "answer": "Docetaxel monotherapy is an established second- or later-line therapy for advanced NSCLC, offering a straightforward comparison to Adagrasib monotherapy."
+    },
+    {
+      "question": "How might these PICO exercises inform future European Joint Clinical Assessments?",
+      "answer": "They provide a framework for systematically evaluating interventions, comparators, and outcomes, potentially shaping standardized procedures in Joint Clinical Assessments."
+    },
+    {
+      "question": "Why are there so many PICOs focusing on subpopulations in advanced NSCLC?",
+      "answer": "Advanced NSCLC patients may differ by histology, PD-L1 status, and prior treatments, so multiple PICOs ensure coverage of all relevant clinical scenarios."
+    },
+    {
+      "question": "In which PICO is docetaxel in combination with nintedanib included outside of PICO 9?",
+      "answer": "PICO 11 and PICO 13 also mention docetaxel plus nintedanib as a comparator for certain subgroups, primarily those with adenocarcinoma histology."
+    },
+    {
+      "question": "Is there a specific mention of head-to-head trials between Adagrasib and docetaxel plus nintedanib?",
+      "answer": "Not specifically. The PICO proposes such comparisons but does not confirm any actual head-to-head clinical studies."
+    },
+    {
+      "question": "What are the key safety endpoints beyond just reporting adverse events?",
+      "answer": "Key safety endpoints include serious AEs, severe AEs by organ class, deaths due to AEs, treatment discontinuations, interruptions, and dose reductions."
+    },
+    {
+      "question": "Does the document specify how to handle crossover treatments in these PICOs?",
+      "answer": "No guidance on crossover is provided; the PICO exercises mainly define intervention and comparator arms for standard clinical trial designs."
+    },
+    {
+      "question": "How might the iterative nature of these exercises improve the final guidance?",
+      "answer": "By continuously integrating feedback and lessons learned, the final guidance becomes more robust, comprehensive, and reflective of real-world clinical complexities."
+    },
+    {
+      "question": "What is a possible reason these exercises were published if they do not reflect the final version?",
+      "answer": "They were published for transparency, showing the process and rationale behind scoping decisions and how the guidance evolved over time."
+    },
+    {
+      "question": "Which PICO might a clinician consider if a patient progressed on both immune checkpoint inhibitors and platinum-based chemotherapy used separately?",
+      "answer": "PICO 13 addresses patients who received a PD-1/PD-L1 antibody in combination with, or sequentially with, platinum-containing chemotherapy."
+    },
+    {
+      "question": "In general, what is the role of the outcomes list provided in the document?",
+      "answer": "The outcomes list guides sponsors and assessors on what clinical endpoints to measure, ensuring comprehensive evaluation of benefits and risks."
+    },
+    {
+      "question": "Are any biomarker-driven therapies other than KRAS G12C inhibitors discussed in these PICOs?",
+      "answer": "No; the focus is specifically on Adagrasib for the KRAS G12C mutation and comparing it to standard or relevant advanced NSCLC treatments."
+    },
+    {
+      "question": "Why is 'time-to-progression on subsequent treatment line' included?",
+      "answer": "It helps assess whether initial therapy with Adagrasib might extend time before the cancer advances again on a new regimen, an indirect marker of long-term benefit."
+    },
+    {
+      "question": "What is the main lesson for HTA bodies from these exercises?",
+      "answer": "HTA bodies can see how structured PICOs might streamline and unify evidence requirements, aiding in consistent and transparent clinical assessments."
+    },
+    {
+      "question": "Do the exercises provide any final conclusions on the clinical value of Adagrasib?",
+      "answer": "No, the exercises only outline how to compare and assess Adagrasib; they do not present final evaluative conclusions or recommendations."
+    },
+    {
+      "question": "Which PICO deals with subpopulations who specifically did not get prior immunotherapy, only chemotherapy?",
+      "answer": "Most PICOs address patients who have had various prior therapies; PICO 2 is the simplest scenario focusing on platinum doublet as a comparator, implying prior therapy but not specifically immunotherapy."
+    },
+    {
+      "question": "Does the guidance say anything about the statistical methods to be used for these comparisons?",
+      "answer": "No specific statistical methods are mentioned; the guidance focuses on defining populations, interventions, comparators, and outcomes."
+    },
+    {
+      "question": "Why is there a caution that the published PICO exercises do not fully reflect the final guidance?",
+      "answer": "The guidance was finalized after incorporating all lessons from these exercises, so the published exercises may differ from the ultimate recommendations."
+    },
+    {
+      "question": "How might these PICO exercises benefit companies seeking marketing authorization for new therapies?",
+      "answer": "They illustrate how to structure submissions in a way that matches the scoping guidance, potentially simplifying joint clinical assessments in the future."
+    },
+    {
+      "question": "What is the importance of noting this was an ‘exercise’ rather than an official assessment?",
+      "answer": "Labeling it as an exercise clarifies that outcomes are hypothetical for learning purposes and do not carry regulatory or reimbursement weight."
     }
-]
+  ]
+