Dissemination of Information on Potentially Fatal Adverse Drug Reactions for Cancer Drugs From 2000 to 2002: First Results From the Research on Adverse Drug Events and Reports Project

2003 ◽  
Vol 21 (20) ◽  
pp. 3859-3866 ◽  
Author(s):  
Lisa A. Ladewski ◽  
Steven M. Belknap ◽  
Jonathan R. Nebeker ◽  
Oliver Sartor ◽  
E. Allison Lyons ◽  
...  
Keyword(s):  
Adverse Drug Reactions ◽  
Adverse Drug Events ◽  
Package Insert ◽  
Clinical Findings ◽  
Cancer Drug ◽  
Cancer Drugs ◽  
Journal Articles ◽  
Drug Reactions ◽  
Fda Approval ◽  
First Results

Purpose: To describe the clinical findings, occurrence rates, causality evidence, and dissemination media for serious cancer drug–associated adverse drug reactions (ADRs) reported in the postmarketing setting. Methods: ADRs were termed serious if they resulted in death or severe organ failure. ADR information for oncology drugs from package insert (PI) revisions, so-called Dear Doctor letters, and journal articles was evaluated to identify serious ADRs reported from 2000 to 2002. Timing and content of information disseminated was assessed. Results: Twenty-five serious ADRs associated with 22 oncology drugs were identified after approval. Approximately half of these serious ADRs are associated with drugs approved before 1995. ADRs were described in articles in medical journals (17 ADRs), PI revisions (18 ADRs), and Dear Doctor letters (12 ADRs). PI revisions occurred less than 1 year after peer-reviewed publication for four ADRs. These revisions often differed for similar ADRs that occurred with drugs of the same class. Five of the seven ADRs lacking PI changes occurred with off-label use, for which PI change is not recommended by US Food and Drug Administration (FDA) policy. No cancer drug was withdrawn from the market during the observation period. Conclusion: Our findings demonstrate that serious ADRs may be discovered as long as 36 years after a drug receives FDA approval. This suggests a need for continued vigilance and efficient strategies for dissemination of information about ADRs associated with cancer drugs.

Clinical trials, case reports, and observational databases as sources of information on serious cancer-related adverse drug reactions (sADRs): Lessons learned from the Research on Adverse Drug Events and Reports (RADAR) project

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 19591-19591
Author(s):  
C. Bennett ◽  
K. Gleason ◽  
B. Djulbegovic ◽  
D. Raisch
Keyword(s):  
Organ Failure ◽  
Adverse Drug Reactions ◽  
Adverse Drug Events ◽  
Case Reports ◽  
Clinical Information ◽  
Lessons Learned ◽  
Sources Of Information ◽  
Drug Reactions ◽  
Fda Approval ◽  
Black Box Warnings

19591 Background: Serious adverse drug reactions (sADRs) such as venous thromboembolism resulting from cancer pharmaceutical use are underappreciated and often misattributed to the cancer diagnosis, rather than the therapy. The Research on Adverse Drug events And Reports (RADAR) group evaluated factors associated with identification of serious cancer-related sADRs (i.e. an adverse drug reaction that results in death or severe organ failure). Methods: Information on sources of clinical information, incidence, setting, and time from FDA approval to initial identification was obtained for sADRs that resulted in death or severe organ failure. Most of the ADRs are described as Black Box warnings or in “Dear Doctor” letters. Results: Summarized in table . Conclusion: Clinical trial safety reports from off-label settings facilitate identification of common (>3% rate) cancer associated sADRs. Case reports and observational databases from on-label settings facilitate detection of rare cancer-associated sADRs (<1%) often at lengthy time intervals from initial FDA approval. No significant financial relationships to disclose. [Table: see text]

Differences in safety profiles of newly approved medications for multiple myeloma in real-world settings versus randomized controlled trials

2020 ◽  
pp. 107815522094193
Author(s):  
Eric P Borrelli ◽  
Conor G McGladrigan
Keyword(s):  
Multiple Myeloma ◽  
Randomized Controlled Trials ◽  
Adverse Drug Reactions ◽  
Malignant Neoplasm ◽  
Controlled Trials ◽  
Site Reaction ◽  
Drug Reactions ◽  
Infusion Site ◽  
Randomized Controlled ◽  
Fda Approval

Background Four new agents (elotuzumab, ixazomib, panobinostat, and daratumumab) were approved by the US Food and Drug Administration (FDA) in 2015 for the treatment of multiple myeloma. Our objective was to compare the safety profiles of these new medications in real-world settings and their randomized controlled trial(s). Material and methods An analysis was conducted of the FDA Adverse Event Reporting System (FAERS) for each drug consisting of the quarter that the drug received its FDA approval and the eight subsequent quarters. Reporting odds ratios and corresponding 95% confidence intervals were then calculated for each drug for each of the 10 most frequent adverse drug reactions. The randomized controlled trials that led to initial FDA approval for these medications were subsequently reviewed to assess the 10 most frequently reported adverse drug reactions in these trials. Results There were only two adverse drug reactions in the top 10 of both FAERS and its randomized controlled trials for elotuzumab (anaemia, diarrhoea) and for daratumumab (cough, back pain), five for ixazomib (diarrhoea, constipation, fatigue, nausea, peripheral neuropathy), and four panobinostat (diarrhoea, fatigue, nausea, constipation). Ixazomib had two adverse drug reactions with a significant reporting odds ratios greater than a 10-fold increased risk (plasma cell myeloma, peripheral neuropathy); elotuzumab had three adverse drug reactions (infusion site reaction, malignant neoplasm progression, deep vein thrombosis); daratumumab had three adverse drug reactions (infusion site reaction, bronchospasm, chills), while panobinostat had four (malignant neoplasm progression, decreased platelet count, diarrhoea, increased blood creatinine). Conclusion This analysis helps to highlight the importance of conducting postmarketing pharmacovigilance studies to better understand the potential adverse reactions of these medications.

Caveat medicus: Harrowing experiences of clinicians who identify and publish near-fatal oncology associated adverse drug reactions.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 6584-6584
Author(s):  
Ashley Caitlin Godwin ◽  
Charles L. Bennett
Keyword(s):  
New England ◽  
Adverse Drug Reactions ◽  
Adverse Drug Events ◽  
Case Series ◽  
Index Patient ◽  
Drug Reactions ◽  
Inclusion Criteria ◽  
Academic Leaders ◽  
Pharmaceutical Manufacturers ◽  
Personal Experiences

6584 Background: Less than 1-10% of adverse drug reactions are reported. It is even more rare to find clinicians who choose to publish these reports in the literature. We identified clinicians who had treated a patient for an oncology-associated serious adverse drug reaction and published these findings. This is the first study that has investigated personal experiences of clinicians choosing to publish information about serious oncology-associated drug reactions they see in their patients. Methods: Clinicians treating individual patients who developed oncology-associated serious adverse drug events were asked to participate. Inclusion criteria included having index patient information, reporting case series, and being collaborative with investigators from two National Institutes of Health funded pharmacovigilance networks. Thirty-minute interviews addressed feedback from pharmaceutical manufacturers, FDA personnel, and academic leadership, and recommendations for improving pharmacovigilance. Responses were analyzed using constant comparative methods of qualitative analysis. Results: 18 clinicians met inclusion criteria and 14 interviewees are included. Toxicities included central nervous system infections, arterial/venous thromboembolism, gastrointestinal toxicity, cardiac arrhythmias, and cancer development/progression. These investigations were frequently followed by label warnings and/or convening of Food and Drug Administration (FDA) Advisory Committee reviews of safety findings. Five studies were disseminated in four high-impact factor medical journals (JAMA, Lancet, Annals of Internal Medicine, and New England Journal of Medicine). Six clinicians received feedback characterized as supportive from academic leaders, while four clinicians received feedback characterized as negative. Responses from pharmaceutical manufacturers were characterized as negative by 12 clinicians. Responses from FDA employees were characterized as negative by six clinicians. Three clinicians recommended that pharmacovigilance should include simplified clinician reporting systems. Conclusions: Our study finds that clinicians who published reports of serious oncology-associated drug reactions experienced negative feedback from pharmaceutical manufacturers. Feedback from FDA employees and academic clinicians were viewed as supportive by some and negative by others. Most clinicians recommended that future pharmacovigilance involve big data analyses.

Timing of US Food and Drug Administration (FDA) cancer drug approvals relative to publication of clinical trial results.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 2071-2071 ◽  
Author(s):  
Ali Raza Khaki ◽  
Aakash Desai ◽  
Martin W. Schoen ◽  
Bishal Gyawali ◽  
Eddy J. Chen ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Cancer Drug ◽  
Cancer Drugs ◽  
Cancer Treatments ◽  
Fda Approval ◽  
Anti Cancer ◽  
Accelerated Approval ◽  
Drug Approvals ◽  
Clinical Trial Results ◽  
Careful Assessment

2071 Background: Publication of clinical trial results in peer reviewed literature is essential to inform clinicians regarding the use of new anti-cancer treatments, which often have a low therapeutic ratio and require careful assessment of risks and benefits. Publication of registration trials should precede FDA approval to facilitate evaluation and implementation of new therapies. The timing of trial publication relative to FDA drug approvals has not been systematically investigated. Methods: We collected all FDA drug approvals for a cancer indication between 2000-19. Trials were identified using FDA labels as well as drugs and publications indexed on HemOnc.org. Approvals for generics/biosimilars, non-oncology indications and label revisions without supportive evidence were excluded. Dates of approval, the approval pathway, approval type (new vs expansion), and the first full publication related to the registration were recorded. Trials and approvals were matched using available metadata. We calculated the proportion of drugs approved prior to publication overall and for those receiving accelerated approval (AA). We used logistic regression to compare rates of pre-publication approval by approval pathway and by new vs expanded approval. Results: Among a total of 378 drug approvals, 139 (37%) had pre-publication approval. Of these, the median overall time from approval to publication was 140 days (IQR 64-281 days). For those with approval after publication, median time from publication to approval was 157 days (IQR 72-359 days). The number of drugs approved pre-publication rose by 27% between the first and last quarters of the study period, though, the proportion decreased as more anti-cancer drugs have been approved in recent years (Table). More drugs were approved pre-publication through AA than regular approval (46% vs 34%, OR 1.66 [95% CI 1.03-2.70], p=0.04) and as new approvals vs. expanded approvals (45% vs 32%, OR 1.76 [95% CI 1.15-2.70], p=0.01). Conclusions: A substantial minority of FDA approvals occur before trial results are published, with the odds being higher for drugs receiving AA and for new approvals. Since clinicians rely upon published results to inform risk/benefit decisions, efforts are needed to ensure trial results are published by the time of FDA approval of new cancer drugs and indications. [Table: see text]

scholarly journals Evaluation of adverse drug reactions of anti-tubercular drugs in the treatment of tuberculosis in tertiary care hospital

2020 ◽  
Vol 9 (9) ◽  
pp. 1430
Author(s):  
Krishnakanth K. ◽  
Jagadeesh A. ◽  
Swetha T. D.
Keyword(s):  
Adverse Drug Reaction ◽  
Adverse Drug Reactions ◽  
Adverse Drug Events ◽  
Tertiary Care Hospital ◽  
Tertiary Care ◽  
Care Hospital ◽  
Drug Reactions ◽  
Cross Sectional ◽  
Medicine Department ◽  
Study Results

Background: Adverse drug reactions are very common among patients on anti-tubercular treatment. Hence, the current study was done to evaluate the adverse drug reaction (ADR) profile in patients receiving anti-tubercular treatment (ATT).Methods: A 6 months prospective, cross-sectional observational study was performed in collaboration with Pulmonology Medicine department. WHO-UMC scale and Naranjo scale was used to evaluate the ADRs.Results: Ninety-two patients receiving ATT presented with 113 adverse drug events (ADE). Males were more affected than females. DOTS category-1 regimen was mostly responsible for ADE. Addition of drugs for the management of ADR events was done.Conclusions: The study results show more ADRs related to ATT demanding increased collaboration between NTEP 2020 and Pharmacovigilance Programme of India to enhance drug safety in this field.

scholarly journals Adverse drug reactions or events in children with assessment of causality and severity: a retrospective analysis from Bhavnagar

2020 ◽  
Vol 9 (12) ◽  
pp. 1883
Author(s):  
Jayendra R. Gohil ◽  
Aniket B. Sarwade ◽  
Hardik R. Chauhan ◽  
Jay R. Jasani ◽  
Hinal R. Gujrati
Keyword(s):  
Adverse Drug Reactions ◽  
Adverse Drug Events ◽  
Tertiary Care Hospital ◽  
Tertiary Care ◽  
Care Hospital ◽  
Drug Reactions ◽  
Pediatric Age Group ◽  
Skin Redness ◽  
The Common ◽  
Probable Category

Background: Objective was to study the occurrence of adverse drug reactions in pediatric age group in a tertiary care hospital setting.Methods: A retrospective study was undertaken to analyze adverse drug events in pediatrics wards of a tertiary care hospital. Any event marked as ‘suspected adverse drug reaction’ was included in the study and ADR forms were analyzed for causality and severity. Other parameters like age and sex, class of drug, types of ADR, commonly involved systems and polypharmacy were studied.Results: Total 74 cases of admitted patients (13 deaths: 11 infants, 6 neonates) with severe ADR were studied of whom 39% were females. Antimicrobials were the commonest drug class (54%) with Skin most commonly involved. 77% cases were of probable category according to Naranjo’s scale of causality assessment. 11% cases were prescribed polypharmacy.Conclusions: Antibiotics were the class of drug causing maximum ADRs. The commonest system involved was skin. Redness, itching & rashes were the common symptoms. Antimicrobials should be used judiciously. Polypharmacy should be avoided. ADR reporting should be strengthened. Extra vigilance is required for infants and neonate’s prescriptions.

Adverse drug reactions and drug interactions

2012 ◽  
Author(s):  
Philip Wiffen ◽  
Marc Mitchell ◽  
Melanie Snelling ◽  
Nicola Stoner
Keyword(s):  
Quality Of Life ◽  
Drug Interactions ◽  
Adverse Drug Reactions ◽  
Adverse Reactions ◽  
Adverse Drug Events ◽  
Hospital Environment ◽  
Drug Reactions ◽  
Significant Cost

Introduction to ADRs 14Classification of ADRs 15Adverse reactions: drug or disease? 16Helping patients understand the risk of ADRs 17Reporting ADRs 18Drug interactions 20Managing drug interactions 23Adverse drug reactions (ADRs), also known as ‘side effects’, ‘adverse drug events’, or ‘drug misadventures’, are a frequent cause of morbidity in hospital and the community. They have a significant cost both financially and in terms of quality of life. Few studies of ADRs have been carried out in the community so the effect on primary care is harder to assess, but studies in the hospital environment have shown the following. ...

Accelerated FDA Approval of Drugs Used To Treat Hematologic Malignancies: Are Policy Changes Needed?.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 266-266 ◽  
Author(s):  
Elizabeth A. Lyons ◽  
June M. McKoy ◽  
Steven Belknap ◽  
Kenneth R. Carson ◽  
Charles L. Bennett
Keyword(s):  
Adverse Drug Reactions ◽  
Overall Response Rate ◽  
Response Rate ◽  
Surrogate Endpoint ◽  
Hematologic Malignancies ◽  
Drug Reactions ◽  
Fda Approval ◽  
Post Marketing ◽  
Accelerated Approval ◽  
Full Approval

Abstract Background: In 1992, the FDA extended the accelerated approval program from HIV and AIDs, to include drugs for other diseases that are serious or life-threatening, appear to provide benefit over available therapy, or for which no other therapy is available. Approval is based on a surrogate endpoint, and pharmaceutical companies are required to confirm safety and efficacy by conducting clinical trials with clinically relevant outcomes. Since 1995, eight drugs used to treat hematologic malignancies have received accelerated approval. Methods: Information available to the public under the Freedom of Information Act was surveyed for new drug applications and supplements for new uses approved by the Division of Oncology Products from January 1, 1995 to August 31, 2003. The package insert and corresponding published literature for the approval of each drug were reviewed for indication, time from drug submission to approval, surrogate endpoint, number of patients in trial, percent response and status of full approval. Results: Of the eight drugs which received accelerated FDA approval, approval was granted within 6 months for three (these also received priority review), 1 was approved within 6–12 months; and 4 were approved after 1 year of FDA review. Approvals were based on the surrogate clinical outcome of response rate. Pivotal studies were often small, with &lt; 100 patients (n=3) and 100–250 patients (n=4). The overall response rate was &lt; 33% for four drugs. Only one of the approvals has been converted to full approval (imatinib). Post-marketing studies have identified three potentially fatal adverse drug reactions related to two drugs (gemtuzumab associated veno-occlusive diesease, gemtuzumab associated severe infusion reactions and imatinib associated upper GI bleeds). Conclusion: To date, accelerated FDA approval for eight hematologic oncology drugs has been granted based on pivotal trials with small sample sizes and low response rates (with the exception of imatinib). Conversion to full approval has rarely occurred (N=1) and post-marketing identification of severe adverse drug reactions, in what were initially off-label settings, has occurred for two of the drugs. Modification of the accelerated approval process for hematologic oncology drugs should be considered. FDA approval information for accelerated approval drugs used to treat hematologic malignancies. Drug Name Indication Time to Approval (Months) N in Trial Overall Response Rate (%) Alemtuzumab CLL 16.5 93 33 Bortezomib Myeloma 3.7 188 14 Cytarabine liposomal Lymphomatous meningitis 5.5 17 41 Denileukin diftitox T-cell lymphoma 14 206 16 Gemtuzumab CD33 positive AML 7 142 26 Ibritumomab tiuxetan Low-grade NHL 15.6 157 62 Imatinib mesylate CML 3 1027 66 Tositumomab NHL 48 40 63

scholarly journals The Effects of Pharmaceutical Marketing and Promotion on Adverse Drug Events and Regulation

2010 ◽  
Vol 2 (4) ◽  
pp. 1-25 ◽  
Author(s):  
Guy David ◽  
Sara Markowitz ◽  
Seth Richards-Shubik
Keyword(s):  
Adverse Drug Reactions ◽  
Adverse Drug Events ◽  
Pharmaceutical Marketing ◽  
Inappropriate Drug ◽  
Pharmaceutical Firm ◽  
Drug Reactions ◽  
Drug Promotion ◽  
Regulatory Interventions ◽  
The Relationship ◽  
Regulatory Actions

This paper analyzes the relationship between postmarketing promotional activity and reporting of adverse drug reactions (ADRs) by modeling the interaction between a regulator (the FDA) and a pharmaceutical firm. Promotion-driven market expansions enhance profitability yet may involve the risk of inappropriate drug prescriptions, leading to regulatory actions against the firm. We empirically test the relationship between drug promotion and reporting of ADRs using an innovative combination of commercial data on pharmaceutical promotion and FDA data on regulatory interventions and ADRs. We provide some evidence that increased levels of promotion and advertising lead to increased reporting of ADRs for certain conditions. (JEL L51, L65, M31, M37)

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