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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... | [] | true | |
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... | [] | true | |
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)... | [] | true | |
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... | [] | true | |
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": "The lower dose 0.75 mg was also recommended for approval because of evidence from Phase III trials of a dose-dependent difference on heart rate and gastrointestinal tolerability between the 0.75 mg and 1.5 mg dose.", "judgment_summary": "The reviewer recommends the 0.75 mg dose for approval due to obs... | true | |
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 ... | [] | true | |
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": "In his review, he describes how assumptions made in handling data in this way could lead to a biased estimate of the treatment effect.",
"judgment_summary": "The reviewer notes that the applicant's method for handling missing data could introduce bias into the treatment effect estimate.",
... | true | |
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:
In light of the statistical and trial design and conduct issues resulting in suboptimal dose titration of the comparator in these open-label trials, I recommend against
.... | [
{
"exact_quote": "In light of the statistical and trial design and conduct issues resulting in suboptimal dose titration of the comparator in these open-label trials, I recommend against",
"judgment_summary": "The reviewer recommends against a specific action or interpretation due to statistical and trial d... | true | |
Trulicity | 125469 | dulaglutide | 8 | 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... | [] | true | |
Trulicity | 125469 | dulaglutide | 9 | 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. This will be reflected in product labeling.",
"judgment_summary": "The reviewer identified specific issues with the trial's statistics, design, and conduct that necessitate... | true | |
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... | [] | true | |
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 ... | [] | true | |
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... | [
{
"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 reviewer identified a deficiency in the non-clinical data supporting the proposed dosing regimen for IPF patients.",
"statement_type": "e... | true | |
Ofev | 205832 | nintedanib | 3 | 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 chronic monkey study failed to identify a NOAEL.",
"judgment_summary": "The reviewer notes that the chronic monkey study did not establish a no-observed-adverse-effect level.",
"statement_type": "explicit_concern",
"topic": "product_quality",
"explicit": true,
"target":... | true | |
Ofev | 205832 | nintedanib | 4 | 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": "The study was not a thorough QT study and did not include a placebo group, positive control, or high dose level (due to ethical reasons).",
"judgment_summary": "The reviewer notes that the QT evaluation study lacked standard design elements such as a placebo group, positive control, and hi... | true | |
Ofev | 205832 | nintedanib | 5 | 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... | [
{
"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 notes a methodological inconsistency where Study 30 relied on investigator reporting for exacerbations rather than independent adjudication u... | true | |
Ofev | 205832 | nintedanib | 6 | 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:
- Table 2. Annual rate of decline in FVC (mL/year) at week 52
| |Nintedanib 150 mg BID|Placebo<br><br>|Difference from Placebo|
|---|---|---|---|
| | | |Adjusted [95% CI] p-value|
|Study 30 Study 32 Study 34|-... | [
{
"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 notes a lack of established knowledge regarding the clinically meaningful effect size for FVC and... | true | |
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:
|Study 32|13 (4.2)|13 (6.4)|0.63 [0.29, 1.36], p=0.288|
|Study 34|22 (6.7)|20 (9.1)|0.74 [0.40, 1.35], p=0.300|
|Study 32+34|35 (5.5)|33 (7.8)|0.70 [0.43, 1.12], p=0.140|
|Study 30+32+34|42 (5.8)|42 (8.3)|0.70 [... | [] | true | |
Ofev | 205832 | nintedanib | 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: 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 submitted data support safety of nintedanib for the treatment of IPF. The major safety findings of note in the program were liver injury, and gastrointestinal adverse reactions.",
"judgment_summary": "The reviewer concludes that the data supports the drug's safety profile while identif... | true | |
Ofev | 205832 | nintedanib | 9 | 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... | [] | true | |
Ofev | 205832 | nintedanib | 10 | 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. | [] | true | |
Ofev | 205832 | nintedanib | 11 | 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... | [] | true | |
Ofev | 205832 | nintedanib | 12 | 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... | [] | true | |
Ofev | 205832 | nintedanib | 13 | 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": "Safety data analysis show liver-related adverse events and gastrointestinal adverse events. For the most part, these appear to be patient tolerability issues, which can be managed by dose adjustment.",
"judgment_summary": "The reviewer identifies liver and gastrointestinal adverse events a... | true | |
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... | [
{
"exact_quote": "This application was discussed at an ODAC meeting on June 25, 2014 where a delay in approval of olaparib was recommended by an 11-2 vote.",
"judgment_summary": "The reviewer notes that the Oncologic Drugs Advisory Committee recommended delaying approval of the drug based on an 11-2 vote.",... | true | |
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 b... | true | |
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... | [] | true | |
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": "Whether the data and analyses from the current submission demonstrated an overall favorable benefit versus risk profile is deferred to the clinical team reviewing this application.",
"judgment_summary": "The statistical reviewer notes that due to the nonrandomized design, no formal compari... | true | |
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": "Based upon these figures, the risk of treating patients with olaparib needs to be weighed against the potential benefit a given patient may expect to gain from this therapy.",
"judgment_summary": "The reviewer emphasizes that the elevated risk of MDS/AML observed in the trials requires car... | true | |
Lynparza | 206162 | olaparib | 5 | 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 ... | true | |
Lynparza | 206162 | olaparib | 6 | 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... | [] | true | |
Lynparza | 206162 | olaparib | 7 | 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... | [] | true | |
Lynparza | 206162 | olaparib | 8 | 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": "Confirmation of clinical benefit will be required as part of accelerated approval.",
"judgment_summary": "The reviewer states that the current evidence is insufficient for full approval and requires future confirmation of clinical benefit.",
"statement_type": "recommendation",
"top... | true | |
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... | [] | true | |
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 ... | [] | true | |
Spinraza | 209531 | nusinersen | 2 | 3. Product Quality | 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: 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-... | [] | true | |
Spinraza | 209531 | nusinersen | 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: 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": "A noteworthy finding in nonclinical studies is neuronal vacuolation in the inferior region of the hippocampus. In some animals, this vacuolation was associated with neuronal and glial cell necrosis and cellular debris. Vacuolation and necrotic cells/cellular debris were still present following... | true | |
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:
Following the highly positive results of the interim analysis, Study CS3B was stopped, with all subjects switched over to receive active treatment with nusinersen.
- Study CS4 in Later-Onset SMA
During th... | [] | true | |
Spinraza | 209531 | nusinersen | 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: 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": "These issues do not outweigh the clear treatment benefit, but justify description in labeling with appropriate risk mitigation recommendations for prescribers.",
"judgment_summary": "The reviewer concludes that identified safety issues require labeling descriptions and risk mitigation desp... | true | |
Spinraza | 209531 | nusinersen | 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: 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. | [] | true | |
Spinraza | 209531 | nusinersen | 7 | 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... | [] | true | |
Spinraza | 209531 | nusinersen | 8 | 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... | true | |
Xarelto | 022406 | rivaroxaban | 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: Xarelto Summary Review
Section heading: 1. Introduction
Page: (unknown)
Text:
Xarelto is an oral Factor Xa inhibitor. Johnson and Johnson Pharmaceutical Research and Development LLC initially submitted this NDA on July 22, 2008 for the prophylaxis of deep vein thrombosis and pulmonary embolism in patients un... | [
{
"exact_quote": "However the application could not be approved during the first cycle due to the need to clarify chemistry, manufacturing and control issues, need for additional understanding of potential safety issues and need for additional clarification of data integrity issues.",
"judgment_summary": "T... | true | |
Xarelto | 022406 | rivaroxaban | 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: Xarelto Summary Review
Section heading: 2. Background
Page: (unknown)
Text:
The FDA has approved four drugs for use in the prevention of venous thromboembolism (VTE) in the setting of hip and/or knee replacement surgery. All these drugs are administered parenterally (enoxaparin, fondaparinux, dalteparin and ... | [
{
"exact_quote": "However, the clinical pharmacology review team recommended and continues to recommend the development of a lower strength formulation for dose modification to be used in certain populations of patients who may be more sensitive to rivaroxaban.",
"judgment_summary": "The reviewer recommends... | true | |
Xarelto | 022406 | rivaroxaban | 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: Xarelto Summary Review
Section heading: 2. Background
Page: (unknown)
Text:
- iii. In addition to any other information within your audit report, address the following questions or requests:
- • At each site audited, how many violations involved each of the following specific issues? For each specific viol... | [] | true | |
Xarelto | 022406 | rivaroxaban | 3 | Clinical Safety 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: Xarelto Summary Review
Section heading: Clinical Safety Issues
Page: (unknown)
Text:
2. The supplied clinical data are insufficient to fully characterize a potential risk for serious liver toxicity. We request the following information:
- a. A report that assesses the potential signal for severe liver toxic... | [
{
"exact_quote": "The supplied clinical data are insufficient to fully characterize a potential risk for serious liver toxicity.",
"judgment_summary": "The reviewer states that the current clinical data package is inadequate to fully assess the risk of serious liver toxicity.",
"statement_type": "explic... | true | |
Xarelto | 022406 | rivaroxaban | 4 | Clinical Pharmacology: | 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: Clinical Pharmacology:
Page: (unknown)
Text:
Provide a description of your plans to develop a lower strength formulation to be used for dose modification in certain special populations of patients.
Carton and Container: Please submit draft labeling revised as follows.... | [
{
"exact_quote": "Provide a description of your plans to develop a lower strength formulation to be used for dose modification in certain special populations of patients.",
"judgment_summary": "The reviewer requests a plan for developing a lower strength formulation to address dose modification needs in spe... | true | |
Xarelto | 022406 | rivaroxaban | 5 | 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: Xarelto Summary Review
Section heading: 3. CMC/Device
Page: (unknown)
Text:
Drs. Crich, Brown, and Pope-Miksinski reviewed this supplement. Dr. Lostritto has also reviewed this supplement. In their reviews they state the following:
From a Chemistry, Manufacturing and Controls standpoint, this NDA is recomme... | [] | true | |
Xarelto | 022406 | rivaroxaban | 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: Xarelto Summary Review
Section heading: 4. Nonclinical Pharmacology/Toxicology
Page: (unknown)
Text:
Drs. Chopra and Laniyonu performed the first cycle review and did not identify any issues that would preclude approval. Drs. Harlow and Papoian reviewed the 2 year carcinogenicity studies in CD-1 Mice and Wis... | [{"exact_quote": "A slight increase in tumors was noted in the Wistar rats study; however, this increase was not statistically significant.", "judgment_summary": "The reviewer notes a slight, non-statistically significant increase in tumors in the Wistar rat study.", "statement_type": "implicit_concern", "topic": "safe... | true | |
Xarelto | 022406 | rivaroxaban | 7 | 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: Xarelto Summary Review
Section heading: 5. Clinical Pharmacology/Biopharmaceutics
Page: (unknown)
Text:
The recommended dose is 10 mg per day with or without food. Dose modification is suggested for those who will take rivaroxaban with a strong PgP and CYP 3A4 inducer.
From the first cycle review:
Dose-dep... | [
{
"exact_quote": "Dose modification is suggested for those who will take rivaroxaban with a strong PgP and CYP 3A4 inducer.",
"judgment_summary": "The reviewer recommends dose adjustments for patients taking rivaroxaban with strong P-gp and CYP3A4 inducers.",
"statement_type": "recommendation",
"top... | true | |
Xarelto | 022406 | rivaroxaban | 8 | 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: Xarelto Summary Review
Section heading: 7. Clinical/Statistical-Efficacy
Page: (unknown)
Text:
I have read the first cycle clinical reviews from Drs. Rieves, Robie-Suh, and Lu. Drs. Lu’s and Robie-Suh’s primary concerns regarding the application were safety, not efficacy. They were concerned that insufficien... | [
{
"exact_quote": "Drs. Lu's and Robie-Suh's primary concerns regarding the application were safety, not efficacy. They were concerned that insufficient safety information on hepatotoxicity was available to assess the full-risk benefit profile.",
"judgment_summary": "Reviewers identified a primary concern re... | true | |
Xarelto | 022406 | rivaroxaban | 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: Xarelto Summary Review
Section heading: 8. Safety
Page: (unknown)
Text:
During the first review cycle, the review team identified several areas for rigorous safety review: bleeding events, cardiovascular events, hepatotoxicity, and renal toxicity.
Bleeding Events: Review of the bleeding events revealed an i... | [
{
"exact_quote": "In subgroup analyses, for Asian subjects and those subjects with body weight ≤ 50 kg or ≥ 110 kg the bleeding risk appeared to be higher for those subjects with rivaroxaban treatment.",
"judgment_summary": "The reviewer identifies a potential increased bleeding risk in specific subgroups (... | true | |
Xarelto | 022406 | rivaroxaban | 10 | 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: Xarelto Summary Review
Section heading: 9. Advisory Committee Meeting
Page: (unknown)
Text:
This product was discussed at a Cardiovascular and Renal Advisory Committee meeting on March 19, 2009. The Committee voted 15 (yes) to 2 (no) that the available clinical data demonstrate a favorable risk-benefit profi... | [] | true | |
Xarelto | 022406 | rivaroxaban | 11 | 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: Xarelto Summary Review
Section heading: 11. Other Relevant Regulatory Issues
Page: (unknown)
Text:
Maternal Health was consulted and provided labeling recommendations which were incorporated into labeling.
Office of Surveillance and Epidemiology was consulted including DMEPA who provided labeling input.
Di... | [
{
"exact_quote": "The data integrity concerns for RECORD 4 involve the following areas:",
"judgment_summary": "The reviewer identifies specific data integrity concerns regarding the RECORD 4 trial.",
"statement_type": "explicit_concern",
"topic": "product_quality",
"explicit": true,
"target"... | true | |
Xarelto | 022406 | rivaroxaban | 12 | 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: Xarelto Summary Review
Section heading: 13. Decision/Action/Risk Benefit Assessment
Page: (unknown)
Text:
- • Recommended regulatory action Approval for the prophylaxis of total VTE for patients undergoing hip surgery and patients undergoing knee surgery
- • Risk Benefit Assessment The risk benefit assessmen... | [
{
"exact_quote": "The most common side effect seen was postoperative bleeding.",
"judgment_summary": "The reviewer identifies postoperative bleeding as the primary safety signal observed in the clinical data.",
"statement_type": "explicit_concern",
"topic": "safety",
"explicit": true,
"targe... | true |
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