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Trulicity | 125469 | dulaglutide | 0 | 1. Introduction | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Trulicity Summary Review
Section heading: 1. Introduction
Page: (unknown)
Text:
On September 18, 2013 Eli Lilly and Company submitted a Biologics License Application (BLA) for Trulicity under section 351 of the Public Health Service Act. The applicant is seeking to indicate Trulicity as an adjunct to diet an... | [] | [] | stop | false | null |
Trulicity | 125469 | dulaglutide | 1 | 2. Background | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Trulicity Summary Review
Section heading: 2. Background
Page: (unknown)
Text:
The drug substance in Trulicity is dulaglutide. In this memorandum, I will use Trulicity and dulaglutide interchangeably. Dulaglutide is a homodimer that consists of two identical polypeptide chains linked to each other by a disulf... | [{"exact_quote": "At the EOP2 meeting the applicant was asked to carry out a dedicated study in patients with renal impairment to adequately evaluate the risk of Trulicity in this population.", "judgment_summary": "The reviewer documents an Agency recommendation to conduct a dedicated study evaluating safety risks in p... | [
{
"exact_quote": "At the EOP2 meeting the applicant was asked to carry out a dedicated study in patients with renal impairment to adequately evaluate the risk of Trulicity in this population.",
"judgment_summary": "The reviewer documents an Agency recommendation to conduct a dedicated study evaluating safet... | stop | false | null |
Trulicity | 125469 | dulaglutide | 2 | 3. CMC/Device | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Trulicity Summary Review
Section heading: 3. CMC/Device
Page: (unknown)
Text:
The drug substance is described in the background section above. The dulaglutide drug substance is manufactured using a mammalian-cell based recombinant expression system (i.e., ) and each polypeptide chain contains an
(b) (4) (b)... | [{"exact_quote": "I concur with the conclusions reached by the product quality teams (Drs. Welch, Chi and Thomas) regarding the acceptability of the manufacturing of the drug product and drug substance.", "judgment_summary": "The reviewer agrees with the product quality team that the manufacturing processes are accepta... | [
{
"exact_quote": "I concur with the conclusions reached by the product quality teams (Drs. Welch, Chi and Thomas) regarding the acceptability of the manufacturing of the drug product and drug substance.",
"judgment_summary": "The reviewer agrees with the product quality team that the manufacturing processes... | stop | false | null |
Trulicity | 125469 | dulaglutide | 3 | 4. Nonclinical Pharmacology/Toxicology | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Trulicity Summary Review
Section heading: 4. Nonclinical Pharmacology/Toxicology
Page: (unknown)
Text:
Dr. Chong has summarized the main nonclinical toxicology findings. Dr. Hummer has reviewed nonclinical pharmacology and toxicology studies in details. The main nonclinical findings relate to the effect of d... | [{"exact_quote": "The non-clinical findings are consistent with other members of the class and the approach to labeling, risk evaluation and mitigation strategy as well as post marketing surveillance will be consistent with other members of the class.", "judgment_summary": "The reviewer recommends that labeling, REMS, ... | [{"exact_quote": "The non-clinical findings are consistent with other members of the class and the approach to labeling, risk evaluation and mitigation strategy as well as post marketing surveillance will be consistent with other members of the class.", "judgment_summary": "The reviewer recommends that labeling, REMS, ... | stop | false | null |
Trulicity | 125469 | dulaglutide | 4 | 5. Clinical Pharmacology/Biopharmaceutics | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Trulicity Summary Review
Section heading: 5. Clinical Pharmacology/Biopharmaceutics
Page: (unknown)
Text:
I concur with the conclusions reached by the clinical pharmacology/biopharmaceutics reviewer (Dr. Sang Chung) that there are no outstanding clinical pharmacology issues that preclude approval. Dulaglutid... | [{"exact_quote": "I concur with the conclusions reached by the clinical pharmacology/biopharmaceutics reviewer (Dr. Sang Chung) that there are no outstanding clinical pharmacology issues that preclude approval.", "judgment_summary": "The reviewer confirms that all clinical pharmacology questions have been adequately ad... | [
{
"exact_quote": "I concur with the conclusions reached by the clinical pharmacology/biopharmaceutics reviewer (Dr. Sang Chung) that there are no outstanding clinical pharmacology issues that preclude approval.",
"judgment_summary": "The reviewer confirms that all clinical pharmacology questions have been a... | stop | false | null |
Trulicity | 125469 | dulaglutide | 5 | 7. Clinical/Statistical-Efficacy | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Trulicity Summary Review
Section heading: 7. Clinical/Statistical-Efficacy
Page: (unknown)
Text:
To support the indication of improved glycemic control, the medium to long term glucose lowering effect of dulaglutide 0.75 mg and 1.5 mg was evaluated in 5 completed phase 3 clinical trials.
The pivotal trials ... | [] | [] | stop | false | null |
Trulicity | 125469 | dulaglutide | 6 | o Double Blind H9X-MC-GBDF- Efficacy assessments at 26 weeks and 52 weeks | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Trulicity Summary Review
Section heading: o Double Blind H9X-MC-GBDF- Efficacy assessments at 26 weeks and 52 weeks
Page: (unknown)
Text:
- 1 HbA1c = Hemoglobin A1c
- 2 OAM = Oral anti-diabetic medication.
- o Compared dulaglutide 0.75 mg and 1.5 mg weekly to placebo (26 weeks) and to sitagliptin 100 mg (5... | [{"exact_quote": "Dr. McEvoy notes that the endpoint analyzed was not strictly speaking the change in HbA1c from baseline to the landmark visit but in actuality could reflect the change from baseline to either the landmark visit, the onset of rescue (for subjects rescued) or the last on study visit (for subjects who di... | [
{
"exact_quote": "Dr. McEvoy notes that the endpoint analyzed was not strictly speaking the change in HbA1c from baseline to the landmark visit but in actuality could reflect the change from baseline to either the landmark visit, the onset of rescue (for subjects rescued) or the last on study visit (for subject... | stop | false | null |
Trulicity | 125469 | dulaglutide | 7 | o Double Blind H9X-MC-GBDF- Efficacy assessments at 26 weeks and 52 weeks | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Trulicity Summary Review
Section heading: o Double Blind H9X-MC-GBDF- Efficacy assessments at 26 weeks and 52 weeks
Page: (unknown)
Text:
I will use the dulaglutide 0.75 mg to metformin comparison to illustrate this. For this comparison, the superiority of dulaglutide 0.75 mg to metformin in HbA1c reduction ... | [{"exact_quote": "For this comparison, the superiority of dulaglutide 0.75 mg to metformin in HbA1c reduction at week 26 was not supported by the prespecified MMRM analysis or the ANCOVA model using LOCF", "judgment_summary": "The primary statistical models failed to demonstrate statistically significant superiority of... | [
{
"exact_quote": "For this comparison, the superiority of dulaglutide 0.75 mg to metformin in HbA1c reduction at week 26 was not supported by the prespecified MMRM analysis or the ANCOVA model using LOCF",
"judgment_summary": "The primary statistical models failed to demonstrate statistically significant su... | stop | false | null |
Trulicity | 125469 | dulaglutide | 8 | o Double Blind H9X-MC-GBDF- Efficacy assessments at 26 weeks and 52 weeks | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Trulicity Summary Review
Section heading: o Double Blind H9X-MC-GBDF- Efficacy assessments at 26 weeks and 52 weeks
Page: (unknown)
Text:
similar intensity of insulin titration (e.g., in the ORIGIN trial for example 50% of enrollees were within FPG goal of 95... | [{"exact_quote": "Achievement of titration goal is likely to be dependent on the adequacy of trial monitoring and on the willingness and motivation of investigators and participants to follow protocol mandated titration algorithms", "judgment_summary": "The reviewer suggests that insufficient monitoring or participant/... | [
{
"exact_quote": "Achievement of titration goal is likely to be dependent on the adequacy of trial monitoring and on the willingness and motivation of investigators and participants to follow protocol mandated titration algorithms",
"judgment_summary": "The reviewer suggests that insufficient monitoring or ... | stop | false | null |
Trulicity | 125469 | dulaglutide | 9 | o Double Blind H9X-MC-GBDF- Efficacy assessments at 26 weeks and 52 weeks | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Trulicity Summary Review
Section heading: o Double Blind H9X-MC-GBDF- Efficacy assessments at 26 weeks and 52 weeks
Page: (unknown)
Text:
8. Safety
Drs. Chong and Balakrishnan have summarized the general safety findings in the application and Dr. Charles the cardiovascular risk analyses specifically. Three ... | [{"exact_quote": "Deaths and serious adverse events were balanced and Dr. Balakrishnan did not note an imbalance for one particular type of serious adverse event.", "judgment_summary": "The reviewer found no imbalance in mortality or serious adverse events across treatment groups.", "statement_type": "positive_assessme... | [{"exact_quote": "Deaths and serious adverse events were balanced and Dr. Balakrishnan did not note an imbalance for one particular type of serious adverse event.", "judgment_summary": "The reviewer found no imbalance in mortality or serious adverse events across treatment groups.", "statement_type": "positive_assessme... | stop | false | null |
Trulicity | 125469 | dulaglutide | 10 | o Double Blind H9X-MC-GBDF- Efficacy assessments at 26 weeks and 52 weeks | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Trulicity Summary Review
Section heading: o Double Blind H9X-MC-GBDF- Efficacy assessments at 26 weeks and 52 weeks
Page: (unknown)
Text:
Elements identified in the review that suggest a causal link between dulaglutide and; injection site, hypersensitivity, gastro-intestinal, and arrhythmia related adverse r... | [{"exact_quote": "Elements identified in the review that suggest a causal link between dulaglutide and; injection site, hypersensitivity, gastro-intestinal, and arrhythmia related adverse reactions as well as increases in amylase and lipase levels 3-fold above the upper limit of normal included; a close temporal associ... | [
{
"exact_quote": "Elements identified in the review that suggest a causal link between dulaglutide and; injection site, hypersensitivity, gastro-intestinal, and arrhythmia related adverse reactions as well as increases in amylase and lipase levels 3-fold above the upper limit of normal included; a close tempora... | stop | false | null |
Trulicity | 125469 | dulaglutide | 11 | o Double Blind H9X-MC-GBDF- Efficacy assessments at 26 weeks and 52 weeks | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Trulicity Summary Review
Section heading: o Double Blind H9X-MC-GBDF- Efficacy assessments at 26 weeks and 52 weeks
Page: (unknown)
Text:
Cardiovascular risk
To meet the requirements outlined in the Guidance to Industry: Diabetes Mellitus – Evaluating Cardiovascular Risk in New Antidiabetic Therapies to Tre... | [{"exact_quote": "The results of this analysis do not suggest that dulaglutide-use is associated with excess CV-risk, as defined in the Guidance, compared to a pool of comparators in the population studied in the Phase 2 and 3 program (relatively low risk population).", "judgment_summary": "The reviewer concludes that ... | [{"exact_quote": "The results of this analysis do not suggest that dulaglutide-use is associated with excess CV-risk, as defined in the Guidance, compared to a pool of comparators in the population studied in the Phase 2 and 3 program (relatively low risk population).", "judgment_summary": "The reviewer concludes that ... | stop | false | null |
Trulicity | 125469 | dulaglutide | 12 | 9. Advisory Committee Meeting | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Trulicity Summary Review
Section heading: 9. Advisory Committee Meeting
Page: (unknown)
Text:
Dulaglutide is the fifth member of the GLP-1 agonist class of anti-diabetic drugs. No new efficacy or safety issue identified in the application rose to the level of requiring the input from an advisory panel. There... | [] | [] | stop | false | null |
Trulicity | 125469 | dulaglutide | 13 | 12. Decision/Action/Risk Benefit Assessment | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Trulicity Summary Review
Section heading: 12. Decision/Action/Risk Benefit Assessment
Page: (unknown)
Text:
- Regulatory Action Approval
- Risk Benefit Assessment Benefits Assessment: The applicant has demonstrated in two adequate and well controlled trials that dulaglutide 0.75 and 1.5 mg administered s... | [{"exact_quote": "statistical, design and conduct issues were identified and are summarized in the efficacy section of this memorandum.", "judgment_summary": "The reviewer identifies statistical, design, and conduct issues in the trials that are detailed elsewhere in the review.", "statement_type": "explicit_concern", ... | [
{
"exact_quote": "statistical, design and conduct issues were identified and are summarized in the efficacy section of this memorandum.",
"judgment_summary": "The reviewer identifies statistical, design, and conduct issues in the trials that are detailed elsewhere in the review.",
"statement_type": "exp... | stop | false | null |
Trulicity | 125469 | dulaglutide | 14 | 12. Decision/Action/Risk Benefit Assessment | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Trulicity Summary Review
Section heading: 12. Decision/Action/Risk Benefit Assessment
Page: (unknown)
Text:
Recommendation for Postmarketing Risk Evaluation and Mitigation Strategies
Dulaglutide will be approved with a Risk Evaluation and Mitigation Strategy (REMS), which consists of a communication plan ... | [{"exact_quote": "Dulaglutide will be approved with a Risk Evaluation and Mitigation Strategy (REMS), which consists of a communication plan to inform health care providers about the serious risks of thyroid C-cell tumors and pancreatitis.", "judgment_summary": "The reviewer recommends a REMS communication plan due to ... | [
{
"exact_quote": "Dulaglutide will be approved with a Risk Evaluation and Mitigation Strategy (REMS), which consists of a communication plan to inform health care providers about the serious risks of thyroid C-cell tumors and pancreatitis.",
"judgment_summary": "The reviewer recommends a REMS communication ... | stop | false | null |
Ofev | 205832 | nintedanib | 0 | 205832Orig1s000 | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Ofev Summary Review
Section heading: 205832Orig1s000
Page: (unknown)
Text:
SUMMARY REVIEW
SUMMARY REVIEW OF REGULATORY ACTION Date: October 10, 2014 From: Badrul A. Chowdhury, MD, PhD
Director, Division of Pulmonary, Allergy and Rheumatology Products, CDER, FDA
Subject: Division Director Summary Review ND... | [] | [] | stop | false | null |
Ofev | 205832 | nintedanib | 1 | 1. Introduction | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Ofev Summary Review
Section heading: 1. Introduction
Page: (unknown)
Text:
Boehringer Ingelheim Pharmaceuticals, Inc. (BI) submitted this 505(b)(1) application for use of nintedanib 150 mg and 100 mg capsules for the treatment of patients with idiopathic pulmonary fibrosis (IPF). The proposed dose is 150 mg ... | [] | [] | stop | false | null |
Ofev | 205832 | nintedanib | 2 | 2. Background | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Ofev Summary Review
Section heading: 2. Background
Page: (unknown)
Text:
IPF is a diffuse progressive parenchymal lung disease of unknown etiology, characterized by fibrotic interstitial infiltrates that are consistent with the histopathologic pattern of usual interstitial pneumonia.1 It is the most common t... | [] | [] | stop | false | null |
Ofev | 205832 | nintedanib | 3 | 2. Background | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Ofev Summary Review
Section heading: 2. Background
Page: (unknown)
Text:
Pertinent regulatory interactions between BI and the Agency include a Pre-IND Meeting in August 2006, End-of-Phase 2 (EOP2) Meeting in December 2010, and a Pre-NDA meeting in October 2013. At the Pre-IND meeting the Division informed BI... | [{"exact_quote": "At the Pre-IND meeting the Division informed BI that there was a lack of non-clinical support for dosing in IPF patients.", "judgment_summary": "The Division identified insufficient non-clinical data to justify the proposed dosing regimen for IPF patients.", "statement_type": "explicit_concern", "topi... | [
{
"exact_quote": "At the Pre-IND meeting the Division informed BI that there was a lack of non-clinical support for dosing in IPF patients.",
"judgment_summary": "The Division identified insufficient non-clinical data to justify the proposed dosing regimen for IPF patients.",
"statement_type": "explicit... | stop | false | null |
Ofev | 205832 | nintedanib | 4 | 2. Background | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Ofev Summary Review
Section heading: 2. Background
Page: (unknown)
Text:
(b) (4)
(b) (4)
The packaging will be performed at the BI Pharma site in Germany. All manufacturing and testing facilities associated with this application have acceptable inspection status. The various DMFs associated with the manufa... | [] | [] | stop | false | null |
Ofev | 205832 | nintedanib | 5 | 4. Nonclinical Pharmacology and Toxicology | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Ofev Summary Review
Section heading: 4. Nonclinical Pharmacology and Toxicology
Page: (unknown)
Text:
BI submitted a complete toxicology program that included general toxicology studies in mice, rats, and monkeys for up to 12 months; reproductive and developmental toxicology studies in rats and rabbits; and ... | [{"exact_quote": "The only observation in monkeys at the low dose of 10 mg/kg/day was growth plate thickening, which is unlikely to be relevant to an older adult population.", "judgment_summary": "The reviewer concludes that the observed growth plate thickening in monkeys at low doses is not clinically relevant to the ... | [
{
"exact_quote": "The only observation in monkeys at the low dose of 10 mg/kg/day was growth plate thickening, which is unlikely to be relevant to an older adult population.",
"judgment_summary": "The reviewer concludes that the observed growth plate thickening in monkeys at low doses is not clinically rele... | stop | false | null |
Ofev | 205832 | nintedanib | 6 | 5. Clinical Pharmacology and Biopharmaceutics | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Ofev Summary Review
Section heading: 5. Clinical Pharmacology and Biopharmaceutics
Page: (unknown)
Text:
BI submitted a complete and adequate clinical pharmacology program for nintedanib. Nintedanib will be recommended for administration with food, as coadministration with food increased exposure (AUC and Cm... | [{"exact_quote": "Nintedanib will be recommended for administration with food, as coadministration with food increased exposure (AUC and Cmax by 20%).", "judgment_summary": "The reviewer recommends that the product be administered with food due to a clinically relevant increase in systemic exposure.", "statement_type":... | [
{
"exact_quote": "Nintedanib will be recommended for administration with food, as coadministration with food increased exposure (AUC and Cmax by 20%).",
"judgment_summary": "The reviewer recommends that the product be administered with food due to a clinically relevant increase in systemic exposure.",
"... | stop | false | null |
Ofev | 205832 | nintedanib | 7 | 7. Clinical and Statistical – Efficacy | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Ofev Summary Review
Section heading: 7. Clinical and Statistical – Efficacy
Page: (unknown)
Text:
a. Overview of the clinical program Some characteristics of the relevant clinical studies that form the basis of review and regulatory decision for this application are shown in Table 1. The design and conduct o... | [] | [] | stop | false | null |
Ofev | 205832 | nintedanib | 8 | 7. Clinical and Statistical – Efficacy | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Ofev Summary Review
Section heading: 7. Clinical and Statistical – Efficacy
Page: (unknown)
Text:
- b. Design and conduct of the studies
Studies 30, 32, and 34 were similar in design and conduct except for the treatment arms as noted in Table 1. All three studies were randomized, double-blind, placebo-cont... | [{"exact_quote": "Time to first IPF exacerbation was adjudicated in Studies 32 and 34, but investigator-reported only in Study 30.", "judgment_summary": "The reviewer implies that relying solely on investigator-reported exacerbations in Study 30, unlike the adjudicated approach in the other studies, may limit endpoint ... | [{"exact_quote": "Time to first IPF exacerbation was adjudicated in Studies 32 and 34, but investigator-reported only in Study 30.", "judgment_summary": "The reviewer implies that relying solely on investigator-reported exacerbations in Study 30, unlike the adjudicated approach in the other studies, may limit endpoint ... | stop | false | null |
Ofev | 205832 | nintedanib | 9 | 7. Clinical and Statistical – Efficacy | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Ofev Summary Review
Section heading: 7. Clinical and Statistical – Efficacy
Page: (unknown)
Text:
- c. Efficacy findings and conclusions
The submitted clinical program supports efficacy of nintedanib at a dose of 150 mg BID. Dose ranging in IPF patients was conducted in Study 30 (Table 1). From an efficacy... | [{"exact_quote": "The proposed starting dose of 150 mg BID for phase 3 studies was reasonable because of the increased efficacy with respect to annual rate of decline in FVC for the 150 mg BID group compared to the 100 mg BID and other lower dose groups.", "judgment_summary": "The reviewer judges that the applicant's s... | [
{
"exact_quote": "The proposed starting dose of 150 mg BID for phase 3 studies was reasonable because of the increased efficacy with respect to annual rate of decline in FVC for the 150 mg BID group compared to the 100 mg BID and other lower dose groups.",
"judgment_summary": "The reviewer judges that the a... | stop | false | null |
Ofev | 205832 | nintedanib | 10 | 7. Clinical and Statistical – Efficacy | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Ofev Summary Review
Section heading: 7. Clinical and Statistical – Efficacy
Page: (unknown)
Text:
| |Nintedanib 150 mg BID|Placebo<br><br>|Difference from Placebo|
|---|---|---|---|
| | | |Adjusted [95% CI] p-value|
|height, and random effect of patient-specific intercept and time. Study 30 was based on an M... | [{"exact_quote": "The absolute effect size for FVC that can be considered clinically meaningful and correlates with mortality or other patient-centered outcomes is not known.", "judgment_summary": "The reviewer identifies a limitation regarding the unknown clinical meaningfulness of the FVC effect size and its correlat... | [
{
"exact_quote": "The absolute effect size for FVC that can be considered clinically meaningful and correlates with mortality or other patient-centered outcomes is not known.",
"judgment_summary": "The reviewer identifies a limitation regarding the unknown clinical meaningfulness of the FVC effect size and ... | stop | false | null |
Ofev | 205832 | nintedanib | 11 | 7. Clinical and Statistical – Efficacy | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Ofev Summary Review
Section heading: 7. Clinical and Statistical – Efficacy
Page: (unknown)
Text:
| |Nintedanib 150 mg BID|Placebo|Difference from Placebo|
|---|---|---|---|
| | | |Hazard Ratio [95% CI] p-value|
|Study 30 Study 32* Study 34*|2 (2.3) 7 (2.3) 5 (1.5)<br><br>|12 (13.8) 8 (3.9) 16 (7.3)|0.16 [0.... | [{"exact_quote": "SGRQ was not developed specifically for use in IPF patients.", "judgment_summary": "The reviewer identifies a limitation in the applicability and validation of the SGRQ patient-reported outcome instrument for the IPF population.", "statement_type": "implicit_concern", "topic": "trial_design", "explici... | [
{
"exact_quote": "SGRQ was not developed specifically for use in IPF patients.",
"judgment_summary": "The reviewer identifies a limitation in the applicability and validation of the SGRQ patient-reported outcome instrument for the IPF population.",
"statement_type": "implicit_concern",
"topic": "tri... | stop | false | null |
Ofev | 205832 | nintedanib | 12 | 7. Clinical and Statistical – Efficacy | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Ofev Summary Review
Section heading: 7. Clinical and Statistical – Efficacy
Page: (unknown)
Text:
In the analysis of all-cause mortality measured at vital status, mortality benefit was not demonstrated for the three studies individually or pooled. The numerical trend generally favored nintedanib, but the con... | [{"exact_quote": "The numerical trend generally favored nintedanib, but the confidence intervals were large.", "judgment_summary": "The reviewer notes that wide confidence intervals reduce the precision and statistical certainty of the observed mortality trend.", "statement_type": "implicit_concern", "topic": "statisti... | [
{
"exact_quote": "The numerical trend generally favored nintedanib, but the confidence intervals were large.",
"judgment_summary": "The reviewer notes that wide confidence intervals reduce the precision and statistical certainty of the observed mortality trend.",
"statement_type": "implicit_concern",
... | stop | false | null |
Ofev | 205832 | nintedanib | 13 | 8. Safety | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Ofev Summary Review
Section heading: 8. Safety
Page: (unknown)
Text:
- a. Safety database
The safety assessment of nintedanib was primarily based on studies shown in Table 1. The total number of patients exposed to nintedanib is reasonable to assess safety.
- b. Safety findings and conclusion
The submitt... | [{"exact_quote": "The major safety findings of note in the program were liver injury, and gastrointestinal adverse reactions.", "judgment_summary": "The reviewer highlights liver injury and gastrointestinal adverse reactions as the primary safety signals requiring attention.", "statement_type": "implicit_concern", "top... | [
{
"exact_quote": "The major safety findings of note in the program were liver injury, and gastrointestinal adverse reactions.",
"judgment_summary": "The reviewer highlights liver injury and gastrointestinal adverse reactions as the primary safety signals requiring attention.",
"statement_type": "implici... | stop | false | null |
Ofev | 205832 | nintedanib | 14 | 8. Safety | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Ofev Summary Review
Section heading: 8. Safety
Page: (unknown)
Text:
5% and more frequently in nintedanib versus placebotreated patient, in order of decreasing frequency, were: diarrhea, nausea, abdominal pain, vomiting, liver enzyme elevation, decreased appetite, headache, decreased weight, and hypertension... | [{"exact_quote": "Embryofetal toxicity: Animal reproductive and developmental toxicology studies demonstrated that nintedanib was a teratogen.", "judgment_summary": "The reviewer identifies teratogenicity observed in animal studies as a significant safety finding requiring mitigation.", "statement_type": "explicit_conc... | [
{
"exact_quote": "Embryofetal toxicity: Animal reproductive and developmental toxicology studies demonstrated that nintedanib was a teratogen.",
"judgment_summary": "The reviewer identifies teratogenicity observed in animal studies as a significant safety finding requiring mitigation.",
"statement_type"... | stop | false | null |
Ofev | 205832 | nintedanib | 15 | 9. Advisory Committee Meeting | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Ofev Summary Review
Section heading: 9. Advisory Committee Meeting
Page: (unknown)
Text:
A Pulmonary-Allergy Drugs Advisory Committee (PADAC) meeting was not held to discuss the nintedanib IPF application. The clinical program showed convincing benefit in FVC, which was supported by numerical trends in favor... | [{"exact_quote": "The clinical program showed convincing benefit in FVC, which was supported by numerical trends in favor of mortality, and other secondary efficacy measures.", "judgment_summary": "The mortality benefit was observed only as numerical trends rather than statistically confirmed results.", "statement_type... | [
{
"exact_quote": "The clinical program showed convincing benefit in FVC, which was supported by numerical trends in favor of mortality, and other secondary efficacy measures.",
"judgment_summary": "The mortality benefit was observed only as numerical trends rather than statistically confirmed results.",
... | stop | false | null |
Ofev | 205832 | nintedanib | 16 | 10. Pediatric | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Ofev Summary Review
Section heading: 10. Pediatric
Page: (unknown)
Text:
Specific pediatric studies are not necessary because IPF is a disease of adults and does not occur in the pediatric population. Furthermore, as an orphan drug program, pediatric studies are not required. | [] | [] | stop | false | null |
Ofev | 205832 | nintedanib | 17 | 11. Other Relevant Regulatory Issues | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Ofev Summary Review
Section heading: 11. Other Relevant Regulatory Issues
Page: (unknown)
Text:
- a. DSI Audits
A high level DSI audit of the Applicant was requested during review of the NDA. Audit of individual sites were not done because the number of patients enrolled in any specific site was small and t... | [{"exact_quote": "Minor deficiencies were noted, but these were isolated and deemed unlikely to impact data integrity and patient safety.", "judgment_summary": "The reviewer acknowledges minor audit deficiencies but concludes they are isolated and do not compromise data integrity or patient safety.", "statement_type": ... | [
{
"exact_quote": "Minor deficiencies were noted, but these were isolated and deemed unlikely to impact data integrity and patient safety.",
"judgment_summary": "The reviewer acknowledges minor audit deficiencies but concludes they are isolated and do not compromise data integrity or patient safety.",
"s... | stop | false | null |
Ofev | 205832 | nintedanib | 18 | 12. Labeling | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Ofev Summary Review
Section heading: 12. Labeling
Page: (unknown)
Text:
- a. Proprietary Name
There are no issues with the proposed proprietary name Ofev. The proposed proprietary name was accepted by the DMEPA.
- b. Physician Labeling
The applicant submitted a label in the Physician’s Labeling Rule forma... | [{"exact_quote": "Various changes to different sections of the label submitted by the Applicant were made to reflect the data accurately and to better communicate the findings to the healthcare providers.", "judgment_summary": "Reviewers determined that the initial label submission lacked sufficient accuracy and clarit... | [
{
"exact_quote": "Various changes to different sections of the label submitted by the Applicant were made to reflect the data accurately and to better communicate the findings to the healthcare providers.",
"judgment_summary": "Reviewers determined that the initial label submission lacked sufficient accurac... | stop | false | null |
Ofev | 205832 | nintedanib | 19 | 13. Action and Risk Benefit Assessment | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Ofev Summary Review
Section heading: 13. Action and Risk Benefit Assessment
Page: (unknown)
Text:
- a. Regulatory Action
The Applicant has submitted adequate efficacy data to support approval of nintedanib for the treatment of IPF. The recommended action on this application is Approval.
- b. Risk Benefit A... | [{"exact_quote": "For the most part, these appear to be patient tolerability issues, which can be managed by dose adjustment.", "judgment_summary": "The reviewer interprets the observed gastrointestinal and liver-related adverse events as primarily tolerability issues that can be mitigated through dose adjustments.", "... | [
{
"exact_quote": "For the most part, these appear to be patient tolerability issues, which can be managed by dose adjustment.",
"judgment_summary": "The reviewer interprets the observed gastrointestinal and liver-related adverse events as primarily tolerability issues that can be mitigated through dose adju... | stop | false | null |
Lynparza | 206162 | olaparib | 0 | 1. Introduction | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Lynparza Summary Review
Section heading: 1. Introduction
Page: (unknown)
Text:
NDA 206162 for the New Molecular Entity (NME), olaparib, was originally submitted for the following indication as proposed by the applicant.
“as monotherapy for the maintenance treatment of adult patients with platinumsensitive r... | [] | [] | stop | false | null |
Lynparza | 206162 | olaparib | 1 | 2. Background | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Lynparza Summary Review
Section heading: 2. Background
Page: (unknown)
Text:
Olaparib is an inhibitor of poly (ADP-ribose) polymerase (PARP) enzymes, including PARP1, PARP2, and PARP3. PARP enzymes are involved in normal cellular homeostasis, such as DNA transcription, cell cycle regulation, and DNA repair. ... | [{"exact_quote": "The accelerated approval of olaparib is recommended based on the results of a single-arm study in patients with deleterious or suspected deleterious gBRCAm advanced cancers which demonstrated a durable 34% response rate.", "judgment_summary": "The reviewer recommends accelerated approval based on a si... | [
{
"exact_quote": "The accelerated approval of olaparib is recommended based on the results of a single-arm study in patients with deleterious or suspected deleterious gBRCAm advanced cancers which demonstrated a durable 34% response rate.",
"judgment_summary": "The reviewer recommends accelerated approval b... | stop | false | null |
Lynparza | 206162 | olaparib | 2 | 5. Clinical Pharmacology/Biopharmaceutics | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Lynparza Summary Review
Section heading: 5. Clinical Pharmacology/Biopharmaceutics
Page: (unknown)
Text:
Elimika Pfuma, PhD, states in her review that the Office of Clinical Pharmacology (Division of Clinical Pharmacology V and Division of Pharmacometrics) has reviewed the information contained in NDA 206162... | [{"exact_quote": "Limited data suggest that the systemic exposure (AUC) of olaparib increases less than proportionally with dose over the dose range of 100 to 400 mg, but the PK data were variable across trials.", "judgment_summary": "The reviewer identifies limited data and cross-trial variability regarding olaparib's... | [{"exact_quote":"Limited data suggest that the systemic exposure (AUC) of olaparib increases less than proportionally with dose over the dose range of 100 to 400 mg, but the PK data were variable across trials.","judgment_summary":"The reviewer identifies limited data and cross-trial variability regarding olaparib's do... | stop | false | null |
Lynparza | 206162 | olaparib | 3 | 7. Clinical/Statistical-Efficacy | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Lynparza Summary Review
Section heading: 7. Clinical/Statistical-Efficacy
Page: (unknown)
Text:
Per the primary clinical review, Study 42 was a single-arm, open-label, multicenter study assessing the response rate of olaparib in patients with advanced cancers who have a deleterious gBRCA mutation. Initially,... | [{"exact_quote": "Hui Zhang, PhD, in her biostatistics review stated that the trial 42 was designed as a nonrandomized study. Therefore, all statistical analyses were descriptive and no formal statistical comparisons were performed.", "judgment_summary": "The nonrandomized study design restricted the statistical evalua... | [
{
"exact_quote": "Hui Zhang, PhD, in her biostatistics review stated that the trial 42 was designed as a nonrandomized study. Therefore, all statistical analyses were descriptive and no formal statistical comparisons were performed.",
"judgment_summary": "The nonrandomized study design restricted the statis... | stop | false | null |
Lynparza | 206162 | olaparib | 4 | 8. Safety | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Lynparza Summary Review
Section heading: 8. Safety
Page: (unknown)
Text:
As per the label, olaparib 400 mg twice daily as monotherapy has been studied in 300 patients with gBRCA-mutated advanced ovarian cancer, and 223 of these patients had received 3 or more prior lines of chemotherapy. In the 223 patients ... | [{"exact_quote": "Per the primary safety review, “the majority of the patients who developed MDS/ AML in this database (17 of 22 patients) have died.", "judgment_summary": "The high mortality rate among patients who developed MDS/AML represents a significant safety concern.", "statement_type": "explicit_concern", "topi... | [
{
"exact_quote": "Per the primary safety review, “the majority of the patients who developed MDS/ AML in this database (17 of 22 patients) have died.",
"judgment_summary": "The high mortality rate among patients who developed MDS/AML represents a significant safety concern.",
"statement_type": "explicit... | stop | false | null |
Lynparza | 206162 | olaparib | 5 | 8. Safety | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Lynparza Summary Review
Section heading: 8. Safety
Page: (unknown)
Text:
As included in the label, pneumonitis, including fatal cases, occurred in <1% of patients treated with olaparib. Per the safety review, “the adverse event of pneumonitis in the context of olaparib therapy is rare; however, five of the t... | [{"exact_quote": "Per the safety review, “the adverse event of pneumonitis in the context of olaparib therapy is rare; however, five of the ten cases (50%) reported had a fatal outcome. Therefore, this event has serious potential consequences for patients.”", "judgment_summary": "The safety reviewer emphasizes that des... | [
{
"exact_quote": "Per the safety review, “the adverse event of pneumonitis in the context of olaparib therapy is rare; however, five of the ten cases (50%) reported had a fatal outcome. Therefore, this event has serious potential consequences for patients.”",
"judgment_summary": "The safety reviewer emphasi... | stop | false | null |
Lynparza | 206162 | olaparib | 6 | 9. Advisory Committee Meeting | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Lynparza Summary Review
Section heading: 9. Advisory Committee Meeting
Page: (unknown)
Text:
The following excerpt from Dr McKee’s CDTL review captures the major points from the ODAC.
The Oncologic Drugs Advisory Committee (ODAC) met June 25, 2014, to discuss NDA
206162. The ODAC was presented data and dis... | [{"exact_quote": "The key issues raised by the FDA review team included loss of randomization for gBRCAm subgroup; estimation of the treatment effect of olaparib therapy; risks of olaparib therapy in the platinumsensitive maintenance setting, including the risk of MDS/AML; and the reproducibility of results in a larger... | [
{
"exact_quote": "The key issues raised by the FDA review team included loss of randomization for gBRCAm subgroup; estimation of the treatment effect of olaparib therapy; risks of olaparib therapy in the platinumsensitive maintenance setting, including the risk of MDS/AML; and the reproducibility of results in ... | stop | false | null |
Lynparza | 206162 | olaparib | 7 | 11. Other Relevant Regulatory Issues | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Lynparza Summary Review
Section heading: 11. Other Relevant Regulatory Issues
Page: (unknown)
Text:
- OSI Audits: As per the clinical review, the Office of Scientific Integrity (OSI) conducted clinical inspections of four clinical sites and the applicant. These sites were that of Dr. Phillip Harter (German... | [{"exact_quote": "After the major amendment was submitted to the NDA, the decision was made to not pursue additional clinical site inspections as there were no major conduct deficiencies at the inspected clinical sites and it is reasonable to assume that the study site conduct would not be drastically different for the... | [
{
"exact_quote": "After the major amendment was submitted to the NDA, the decision was made to not pursue additional clinical site inspections as there were no major conduct deficiencies at the inspected clinical sites and it is reasonable to assume that the study site conduct would not be drastically different... | stop | false | null |
Lynparza | 206162 | olaparib | 8 | 12. Labeling | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Lynparza Summary Review
Section heading: 12. Labeling
Page: (unknown)
Text:
Includes:
- Proprietary name: The Office of Prescription Drug Promotion (OPDP) determined the proposed name is acceptable from a promotional perspective. Per Matthew Davis, Pharm D, DMEPA reviewer, the proposed proprietary name is... | [{"exact_quote": "all labeling issues were resolved during labeling meetings", "judgment_summary": "The reviewer confirms that all previously identified labeling concerns were successfully addressed and settled during collaborative meetings.", "statement_type": "resolution", "topic": "labeling", "explicit": true, "targ... | [
{
"exact_quote": "all labeling issues were resolved during labeling meetings",
"judgment_summary": "The reviewer confirms that all previously identified labeling concerns were successfully addressed and settled during collaborative meetings.",
"statement_type": "resolution",
"topic": "labeling",
... | stop | false | null |
Lynparza | 206162 | olaparib | 9 | 13. Decision/Action/Risk Benefit Assessment | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Lynparza Summary Review
Section heading: 13. Decision/Action/Risk Benefit Assessment
Page: (unknown)
Text:
- Regulatory Action: I recommend an accelerated approval for this NDA.
- Risk Benefit Assessment
As per the primary clinical review, “the observed response rate of 34% in the patients with gBRCAm-a... | [{"exact_quote": "I recommend an accelerated approval for this NDA.", "judgment_summary": "The reviewer recommends granting accelerated approval for the New Drug Application.", "statement_type": "recommendation", "topic": "other", "explicit": true, "target": "approval_decision"}, {"exact_quote": "the observed response ... | [
{
"exact_quote": "I recommend an accelerated approval for this NDA.",
"judgment_summary": "The reviewer recommends granting accelerated approval for the New Drug Application.",
"statement_type": "recommendation",
"topic": "other",
"explicit": true,
"target": "approval_decision"
},
{
... | stop | false | null |
Lynparza | 206162 | olaparib | 10 | 13. Decision/Action/Risk Benefit Assessment | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Lynparza Summary Review
Section heading: 13. Decision/Action/Risk Benefit Assessment
Page: (unknown)
Text:
Submit the progression-free survival (PFS) and overall survival (OS) analyses with datasets from clinical trial D0816C00010, a randomized trial establishing the superiority of olaparib over physician’s ... | [{"exact_quote": "Submit the progression-free survival (PFS) and overall survival (OS) analyses with datasets from clinical trial D0816C00010, a randomized trial establishing the superiority of olaparib over physician’s choice single-agent chemotherapy in the treatment of platinum sensitive relapsed ovarian cancer in p... | [
{
"exact_quote": "Submit the progression-free survival (PFS) and overall survival (OS) analyses with datasets from clinical trial D0816C00010, a randomized trial establishing the superiority of olaparib over physician’s choice single-agent chemotherapy in the treatment of platinum sensitive relapsed ovarian can... | stop | false | null |
Spinraza | 209531 | nusinersen | 0 | 209531Orig1s000 | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Spinraza Summary Review
Section heading: 209531Orig1s000
Page: (unknown)
Text:
SUMMARY REVIEW
|Controlled Substance Staff|Martin Rusinowitz, Michael Klein|
|---|---|
|Cardiac Safety|Christine Garnett, Norman Stockbridge|
|Rare Diseases|Althea Cuff|
|Associat... | [] | [] | stop | false | null |
Spinraza | 209531 | nusinersen | 1 | 1. Benefit-Risk Assessment | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Spinraza Summary Review
Section heading: 1. Benefit-Risk Assessment
Page: (unknown)
Text:
APPEARS THIS WAY ON ORIGINAL
|Benefit-Risk Summary and Assessment<br><br>Spinal muscular atrophy (SMA) is a rare genetic disorder characterized by atrophy of the voluntary muscles of the limbs and trunk. genetic cause ... | [] | [] | stop | false | null |
Spinraza | 209531 | nusinersen | 2 | 1. Benefit-Risk Assessment | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Spinraza Summary Review
Section heading: 1. Benefit-Risk Assessment
Page: (unknown)
Text:
|---|
.
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Spinraza Summary Review
Section heading: 3. Product Quality
Page: (unknown)
Text:
I concur with the conclusions reached by the chemistry reviewer regarding the acceptability of the manufacturing of the drug product and drug substance. Manufacturing site inspections were acceptable. OPQ will grant a month re-... | [] | [] | stop | false | null |
Spinraza | 209531 | nusinersen | 4 | 4. Nonclinical Pharmacology/Toxicology | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Spinraza Summary Review
Section heading: 4. Nonclinical Pharmacology/Toxicology
Page: (unknown)
Text:
I concur with the conclusions reached by the pharmacology/toxicology reviewer that there are no outstanding pharm/tox issues that preclude approval.
A noteworthy finding in nonclinical studies is neuronal v... | [{"exact_quote": "I concur with the conclusions reached by the pharmacology/toxicology reviewer that there are no outstanding pharm/tox issues that preclude approval.", "judgment_summary": "The reviewer confirms that all pharmacology and toxicology issues have been resolved and do not block approval.", "statement_type"... | [
{
"exact_quote": "I concur with the conclusions reached by the pharmacology/toxicology reviewer that there are no outstanding pharm/tox issues that preclude approval.",
"judgment_summary": "The reviewer confirms that all pharmacology and toxicology issues have been resolved and do not block approval.",
... | stop | false | null |
Spinraza | 209531 | nusinersen | 5 | 4. Nonclinical Pharmacology/Toxicology | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Spinraza Summary Review
Section heading: 4. Nonclinical Pharmacology/Toxicology
Page: (unknown)
Text:
Study CS3B in Infantile-Onset SMA
- Study CS3B was a 13-month, multicenter, randomized, double-blind, sham-procedure controlled trial in patients with infantile-onset SMA. Approximately 111 subjects were to... | [{"exact_quote": "That endpoint is very relevant and interpretable clinically, and the separation between the milestones allows a clear assessment of meaningful functional differences.", "judgment_summary": "The reviewer judges the primary motor milestone endpoint to be clinically relevant and interpretable, noting tha... | [
{
"exact_quote": "That endpoint is very relevant and interpretable clinically, and the separation between the milestones allows a clear assessment of meaningful functional differences.",
"judgment_summary": "The reviewer judges the primary motor milestone endpoint to be clinically relevant and interpretable... | stop | false | null |
Spinraza | 209531 | nusinersen | 6 | 4. Nonclinical Pharmacology/Toxicology | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Spinraza Summary Review
Section heading: 4. Nonclinical Pharmacology/Toxicology
Page: (unknown)
Text:
The responder definition for the HINE was met by 41% of nusinersen-treated patients, vs. 0% of patients in the control group (p<0.0001). A sensitivity analysis that includes all patients who died or withdrew... | [{"exact_quote": "This analysis is recommended by the team for description in labeling.", "judgment_summary": "The review team recommends including the sensitivity analysis that accounts for patients who died or withdrew in the product labeling.", "statement_type": "recommendation", "topic": "labeling", "explicit": tru... | [
{
"exact_quote": "This analysis is recommended by the team for description in labeling.",
"judgment_summary": "The review team recommends including the sensitivity analysis that accounts for patients who died or withdrew in the product labeling.",
"statement_type": "recommendation",
"topic": "labeli... | stop | false | null |
Spinraza | 209531 | nusinersen | 7 | 4. Nonclinical Pharmacology/Toxicology | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Spinraza Summary Review
Section heading: 4. Nonclinical Pharmacology/Toxicology
Page: (unknown)
Text:
Other studies
The applicant has conducted several additional open-label studies with nusinersen, covering a broad range of age groups, from presymptomatic infantile-onset (genetically diagnosed) SMA to late... | [] | [] | stop | false | null |
Spinraza | 209531 | nusinersen | 8 | 8. Safety | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Spinraza Summary Review
Section heading: 8. Safety
Page: (unknown)
Text:
I agree with the review team that the size of the safety database is acceptable for this indication. Out of 173 patients in the database, 82 were exposed for ≥ 12 months, mostly at the 12 mg dose proposed for marketing. As discussed abo... | [{"exact_quote": "The review team identified a few significant safety issues with nusinersen.", "judgment_summary": "The reviewer acknowledges that notable safety issues have been identified for the drug.", "statement_type": "explicit_concern", "topic": "safety", "explicit": true, "target": "overall safety profile"}, {... | [
{
"exact_quote": "The review team identified a few significant safety issues with nusinersen.",
"judgment_summary": "The reviewer acknowledges that notable safety issues have been identified for the drug.",
"statement_type": "explicit_concern",
"topic": "safety",
"explicit": true,
"target": ... | stop | false | null |
Spinraza | 209531 | nusinersen | 9 | 8. Safety | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Spinraza Summary Review
Section heading: 8. Safety
Page: (unknown)
Text:
- Effect on growth: In Study CS3B, nusinersen-treated subjects had reduced growth compared with sham-procedure controls. This observation is somewhat surprising, considering the robust effect of nusinersen on spinal muscular atrophy, ... | [{"exact_quote": "This observation is somewhat surprising, considering the robust effect of nusinersen on spinal muscular atrophy, which would be expected to improve growth in treated patients.", "judgment_summary": "The reviewer notes that the observed growth reduction in treated patients contradicts the expected clin... | [
{
"exact_quote": "This observation is somewhat surprising, considering the robust effect of nusinersen on spinal muscular atrophy, which would be expected to improve growth in treated patients.",
"judgment_summary": "The reviewer notes that the observed growth reduction in treated patients contradicts the e... | stop | false | null |
Spinraza | 209531 | nusinersen | 10 | 8. Safety | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Spinraza Summary Review
Section heading: 8. Safety
Page: (unknown)
Text:
Immunogenicity Plasma samples from all clinical studies were analyzed for anti-drug antibody (ADA) presence. Across the safety database, five patients had positive ADA samples. There was no adverse events associated with the presence of... | [{"exact_quote": "The ability of ADA to cross-react with nucleic acids was not evaluated.", "judgment_summary": "The reviewer identifies a gap in the immunogenicity assessment regarding whether the detected antibodies cross-react with nucleic acids.", "statement_type": "explicit_concern", "topic": "safety", "explicit":... | [
{
"exact_quote": "The ability of ADA to cross-react with nucleic acids was not evaluated.",
"judgment_summary": "The reviewer identifies a gap in the immunogenicity assessment regarding whether the detected antibodies cross-react with nucleic acids.",
"statement_type": "explicit_concern",
"topic": "... | stop | false | null |
Spinraza | 209531 | nusinersen | 11 | 9. Advisory Committee Meeting | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Spinraza Summary Review
Section heading: 9. Advisory Committee Meeting
Page: (unknown)
Text:
This application was not referred for review to an advisory committee, because outside expertise was not necessary. There were no controversial issues that would benefit from advisory committee discussion. | [] | [] | stop | false | null |
Spinraza | 209531 | nusinersen | 12 | 10. Other Relevant Regulatory Issues | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Spinraza Summary Review
Section heading: 10. Other Relevant Regulatory Issues
Page: (unknown)
Text:
There are no unresolved regulatory issues. The Office of Scientific Investigations (OSI) has inspected three clinical investigator sites. Data submitted by the applicant in support of the pending application f... | [{"exact_quote": "There are no unresolved regulatory issues.", "judgment_summary": "The reviewer concludes that all regulatory issues for the application have been resolved.", "statement_type": "resolution", "topic": "other", "explicit": true, "target": "regulatory_issues"}, {"exact_quote": "Data submitted by the appli... | [
{
"exact_quote": "There are no unresolved regulatory issues.",
"judgment_summary": "The reviewer concludes that all regulatory issues for the application have been resolved.",
"statement_type": "resolution",
"topic": "other",
"explicit": true,
"target": "regulatory_issues"
},
{
"exac... | stop | false | null |
Spinraza | 209531 | nusinersen | 13 | 12. Postmarketing | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Spinraza Summary Review
Section heading: 12. Postmarketing
Page: (unknown)
Text:
I agree with the review team that a risk evaluation and mitigation strategy (REMS) is not needed for nusinersen, considering the highly specialized setting under which nusinersen will be administered, with regular visits require... | [{"exact_quote": "I agree with the review team that a risk evaluation and mitigation strategy (REMS) is not needed for nusinersen, considering the highly specialized setting under which nusinersen will be administered, with regular visits required for drug administration.", "judgment_summary": "The reviewer concludes t... | [{"exact_quote": "I agree with the review team that a risk evaluation and mitigation strategy (REMS) is not needed for nusinersen, considering the highly specialized setting under which nusinersen will be administered, with regular visits required for drug administration.", "judgment_summary": "The reviewer concludes t... | stop | false | null |
Xarelto | 202439 | rivaroxaban | 0 | Action | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Xarelto Summary Review
Section heading: Action
Page: (unknown)
Text:
This memo conveys the Division’s decision to approve this application and the basis for that decision. During the review of this application, a separate NDA to market XARELTO (rivaroxaban) for prevention of deep venous thrombosis after hip ... | [] | [] | stop | false | null |
Xarelto | 202439 | rivaroxaban | 1 | Introduction | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Xarelto Summary Review
Section heading: Introduction
Page: (unknown)
Text:
Dr. Thompson’s CDTL memo ably reviews the background for and important issues presented by this application and can therefore serve as the summary basis of approval. In this memo, I am not going to summarize systematically the medical... | [{"exact_quote": "Rather I intend to review the salient issues germane to the decision to approve because while the CDTL, Dr. Thompson, recommends approval, the primary clinical reviewers of this application, Drs. Rose and Dunnmon, do not.", "judgment_summary": "The primary clinical reviewers disagree with the medical ... | [
{
"exact_quote": "Rather I intend to review the salient issues germane to the decision to approve because while the CDTL, Dr. Thompson, recommends approval, the primary clinical reviewers of this application, Drs. Rose and Dunnmon, do not.",
"judgment_summary": "The primary clinical reviewers disagree with ... | stop | false | null |
Xarelto | 202439 | rivaroxaban | 2 | Introduction | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Xarelto Summary Review
Section heading: Introduction
Page: (unknown)
Text:
- o In the 30 days after the study ended XARELTO subjects had 22 strokes whereas warfarin subjects had 6 strokes, i.e. XARELTO subjects had nearly four times more strokes.
- Discontinuation of XARELTO may result in a prothrombotic s... | [{"exact_quote": "In the 30 days after the study ended XARELTO subjects had 22 strokes whereas warfarin subjects had 6 strokes, i.e. XARELTO subjects had nearly four times more strokes.", "judgment_summary": "The reviewer highlights a substantially higher post-study stroke rate for Xarelto compared to warfarin, raising... | [
{
"exact_quote": "In the 30 days after the study ended XARELTO subjects had 22 strokes whereas warfarin subjects had 6 strokes, i.e. XARELTO subjects had nearly four times more strokes.",
"judgment_summary": "The reviewer highlights a substantially higher post-study stroke rate for Xarelto compared to warfa... | stop | false | null |
Xarelto | 202439 | rivaroxaban | 3 | TTR as a Metric for Assessing Adequacy of Warfarin Control in Clinical Trials | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Xarelto Summary Review
Section heading: TTR as a Metric for Assessing Adequacy of Warfarin Control in Clinical Trials
Page: (unknown)
Text:
The dose of warfarin must be individualized by adjusting the dose to the INR; too low an INR results in inadequate prevention/treatment of the thrombotic event of intere... | [{"exact_quote": "Comment: A more useful metric than TTR might be a combination of separate measurements of time below therapeutic range and time above therapeutic range weighted according to the clinical consequences of each (i.e., giving more weight to increments in time below the therapeutic range than equivalent in... | [
{
"exact_quote": "Comment: A more useful metric than TTR might be a combination of separate measurements of time below therapeutic range and time above therapeutic range weighted according to the clinical consequences of each (i.e., giving more weight to increments in time below the therapeutic range than equiv... | stop | false | null |
Xarelto | 202439 | rivaroxaban | 4 | TTR as a Metric for Assessing Adequacy of Warfarin Control in Clinical Trials | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Xarelto Summary Review
Section heading: TTR as a Metric for Assessing Adequacy of Warfarin Control in Clinical Trials
Page: (unknown)
Text:
TTR is dependent not only on prescriber skill but also on patient characteristics, such as compliance, concomitant meds, diet, and prior administration of warfarin. For ... | [{"exact_quote": "Thus it is not, and can not be, clear what value of TTR is necessary to determine that warfarin was administered skillfully.", "judgment_summary": "There is no established benchmark for Time in Therapeutic Range to reliably assess whether warfarin was managed optimally in the trial.", "statement_type"... | [
{
"exact_quote": "Thus it is not, and can not be, clear what value of TTR is necessary to determine that warfarin was administered skillfully.",
"judgment_summary": "There is no established benchmark for Time in Therapeutic Range to reliably assess whether warfarin was managed optimally in the trial.",
... | stop | false | null |
Xarelto | 202439 | rivaroxaban | 5 | Application of the 1995 Shultz FR notice | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Xarelto Summary Review
Section heading: Application of the 1995 Shultz FR notice
Page: (unknown)
Text:
The proper application of the 1995 FR notice signed by William Schultz and a contemporary document signed by then President Clinton and Vice President Gore was much discussed by the review team as well as a... | [{"exact_quote": "The application of the Schultz FR notice to NI studies, the only studies possible when there is existing therapy for conditions resulting in mortality or irreversible serious morbidity, is generally not straight-forward.", "judgment_summary": "Applying the regulatory policy framework to noninferiority... | [
{
"exact_quote": "The application of the Schultz FR notice to NI studies, the only studies possible when there is existing therapy for conditions resulting in mortality or irreversible serious morbidity, is generally not straight-forward.",
"judgment_summary": "Applying the regulatory policy framework to no... | stop | false | null |
Xarelto | 202439 | rivaroxaban | 6 | Excess Strokes after Discontinuation of XARELTO at the End of ROCKET-AF | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Xarelto Summary Review
Section heading: Excess Strokes after Discontinuation of XARELTO at the End of ROCKET-AF
Page: (unknown)
Text:
In ROCKET-AF, study drug was discontinued at the end of the study. Subjects on warfarin generally continued on warfarin while warfarin was generally initiated in XARELTO subje... | [{"exact_quote": "In the 30 days after the study ended XARELTO subjects had 22 strokes whereas the warfarin subjects had 6 strokes (i.e. XARELTO subjects had nearly four times more strokes).", "judgment_summary": "The reviewer identifies a significant safety signal characterized by a fourfold increase in stroke events ... | [
{
"exact_quote": "In the 30 days after the study ended XARELTO subjects had 22 strokes whereas the warfarin subjects had 6 strokes (i.e. XARELTO subjects had nearly four times more strokes).",
"judgment_summary": "The reviewer identifies a significant safety signal characterized by a fourfold increase in st... | stop | false | null |
Xarelto | 202439 | rivaroxaban | 7 | Excess Strokes after Discontinuation of XARELTO at the End of ROCKET-AF | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Xarelto Summary Review
Section heading: Excess Strokes after Discontinuation of XARELTO at the End of ROCKET-AF
Page: (unknown)
Text:
The Division received comments from Public Citizen’s Health Research Group indicating concern that the applicant’s failure to “1) pre-specify criteria for transition to approp... | [{"exact_quote": "The Division received comments from Public Citizen’s Health Research Group indicating concern that the applicant’s failure to “1) pre-specify criteria for transition to appropriate anticoagulation in the 30 days following study-drug discontinuation or 2) provide clear, standardized instructions to inv... | [
{
"exact_quote": "The Division received comments from Public Citizen’s Health Research Group indicating concern that the applicant’s failure to “1) pre-specify criteria for transition to appropriate anticoagulation in the 30 days following study-drug discontinuation or 2) provide clear, standardized instruction... | stop | false | null |
Xarelto | 202439 | rivaroxaban | 8 | Switching Patients from XARELTO to Warfarin | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Xarelto Summary Review
Section heading: Switching Patients from XARELTO to Warfarin
Page: (unknown)
Text:
The excess in strokes observed in subjects being switched from XARELTO to warfarin at the end of ROCKET generated discussion both by some of the reviewers of this application as well as some members of t... | [{"exact_quote": "The excess in strokes observed in subjects being switched from XARELTO to warfarin at the end of ROCKET generated discussion both by some of the reviewers of this application as well as some members of the Advisory Committee about the need to conduct a clinical study to identify a protocol for safely ... | [
{
"exact_quote": "The excess in strokes observed in subjects being switched from XARELTO to warfarin at the end of ROCKET generated discussion both by some of the reviewers of this application as well as some members of the Advisory Committee about the need to conduct a clinical study to identify a protocol for... | stop | false | null |
Xarelto | 202439 | rivaroxaban | 9 | Dose of XARELTO administered in ROCKET | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Xarelto Summary Review
Section heading: Dose of XARELTO administered in ROCKET
Page: (unknown)
Text:
Anticoagulants are intrinsically narrow therapeutic range drugs because their principal toxicity, bleeding, is a result of their intended pharmacodynamic activity; too low a dose results in inadequate prevent... | [{"exact_quote": "The Division concurs with all reviewers of this NDA that data adequate to select a dose to be tested in ROCKET were not available when the trial was designed.", "judgment_summary": "Reviewers agree that insufficient data existed at the time of trial design to properly select the test dose.", "statemen... | [
{
"exact_quote": "The Division concurs with all reviewers of this NDA that data adequate to select a dose to be tested in ROCKET were not available when the trial was designed.",
"judgment_summary": "Reviewers agree that insufficient data existed at the time of trial design to properly select the test dose.... | stop | false | null |
Xarelto | 202439 | rivaroxaban | 10 | Dose of XARELTO administered in ROCKET | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Xarelto Summary Review
Section heading: Dose of XARELTO administered in ROCKET
Page: (unknown)
Text:
Comment: It should be noted that the Division routinely advises sponsors to test more than one dose in confirmatory trials of antithrombotics and has even suggested novel trial designs that allow testing of t... | [{"exact_quote": "Multiple antithrombotics have failed to be approved or had low utilization after approval because the doses tested were far from optimal and so it is difficult to understand why sponsors have rarely taken this advice.", "judgment_summary": "The reviewer criticizes the industry practice of testing sing... | [{"exact_quote": "Multiple antithrombotics have failed to be approved or had low utilization after approval because the doses tested were far from optimal and so it is difficult to understand why sponsors have rarely taken this advice.", "judgment_summary": "The reviewer criticizes the industry practice of testing sing... | stop | false | null |
Xarelto | 202439 | rivaroxaban | 11 | Additional Issues Desirability of Monitoring for Adjustment of XARELTO Dose | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Xarelto Summary Review
Section heading: Additional Issues Desirability of Monitoring for Adjustment of XARELTO Dose
Page: (unknown)
Text:
The clinical pharmacology and clinical reviewers demonstrated that there is a linear correlation between rivaroxaban levels and prothrombin time (PT). They also demonstrat... | [{"exact_quote": "This applicant has not chosen to utilize this information.", "judgment_summary": "The reviewer highlights that the applicant did not use the demonstrated PT-drug level-bleeding correlation to guide dosing or monitoring strategies.", "statement_type": "implicit_concern", "topic": "applicant_interpretat... | [{"exact_quote": "This applicant has not chosen to utilize this information.", "judgment_summary": "The reviewer highlights that the applicant did not use the demonstrated PT-drug level-bleeding correlation to guide dosing or monitoring strategies.", "statement_type": "implicit_concern", "topic": "applicant_interpretat... | stop | false | null |
Xarelto | 202439 | rivaroxaban | 12 | Treatment Strategies for XARELTO-Induced Bleeding | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Xarelto Summary Review
Section heading: Treatment Strategies for XARELTO-Induced Bleeding
Page: (unknown)
Text:
The label for COUMADIN provides specific recommendations for treatment of hemorrhage. No such recommendations can be provided for XARELTO. And the label states that XARELTO increases the risk of bl... | [{"exact_quote": "Therefore, it is unlikely that XARELTO will be an appropriate choice for patients at high risk of bleeding.", "judgment_summary": "The reviewer concludes that XARELTO is inappropriate for patients at high bleeding risk due to its higher transfusion risk compared to warfarin.", "statement_type": "expli... | [
{
"exact_quote": "Therefore, it is unlikely that XARELTO will be an appropriate choice for patients at high risk of bleeding.",
"judgment_summary": "The reviewer concludes that XARELTO is inappropriate for patients at high bleeding risk due to its higher transfusion risk compared to warfarin.",
"stateme... | stop | false | null |
Xarelto | 202439 | rivaroxaban | 13 | Analysis of Future Trials of Anticoagulants for Preventing Stroke in Atrial Fibrillation | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Xarelto Summary Review
Section heading: Analysis of Future Trials of Anticoagulants for Preventing Stroke in Atrial Fibrillation
Page: (unknown)
Text:
During the last few years several novel anticoagulants have been under development; two have now been approved, with more likely to come. It strikes this revi... | [{"exact_quote": "It strikes this reviewer that evaluating these drugs by balancing the effect on “stroke” reduction vs “bleeding” is a bit too simple.", "judgment_summary": "The reviewer believes that comparing stroke reduction against overall bleeding risk oversimplifies the evaluation of anticoagulants.", "statement... | [
{
"exact_quote": "It strikes this reviewer that evaluating these drugs by balancing the effect on “stroke” reduction vs “bleeding” is a bit too simple.",
"judgment_summary": "The reviewer believes that comparing stroke reduction against overall bleeding risk oversimplifies the evaluation of anticoagulants."... | stop | false | null |
Xarelto | 202439 | rivaroxaban | 14 | Acknowledgements | null | You are assisting a regulatory science research project that studies how FDA reviewers express judgment in drug review documents (Summary Reviews, Medical, Statistical, Clinical Pharmacology, and Product Quality reviews).
Your task: read a section of an FDA review document and extract every REVIEWER-IDENTIFIED CONCERN... | Document: Xarelto Summary Review
Section heading: Acknowledgements
Page: (unknown)
Text:
The Division’s conclusions rest entirely upon the excellent review performed by this review team. The decision was made difficult by the limitations in the design and conduct of ROCKET AF. Although ultimately coming to a different... | [{"exact_quote": "The decision was made difficult by the limitations in the design and conduct of ROCKET AF.", "judgment_summary": "Limitations in the design and execution of the ROCKET AF trial complicated the regulatory decision.", "statement_type": "explicit_concern", "topic": "trial_design", "explicit": true, "targ... | [
{
"exact_quote": "The decision was made difficult by the limitations in the design and conduct of ROCKET AF.",
"judgment_summary": "Limitations in the design and execution of the ROCKET AF trial complicated the regulatory decision.",
"statement_type": "explicit_concern",
"topic": "trial_design",
... | stop | false | null |
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