Postmarketing Modifications of Drug Labels for Cancer Drugs Approved by the US Food and Drug Administration Between 2006 and 2016 With and Without Supporting Randomized Controlled Trials

2018 ◽  
Vol 36 (18) ◽  
pp. 1798-1804 ◽  
Author(s):  
Daniel Shepshelovich ◽  
Ariadna Tibau ◽  
Hadar Goldvaser ◽  
Consolación Molto ◽  
Alberto Ocana ◽  
...  
Keyword(s):  
Drug Administration ◽  
Health Care Professionals ◽  
Controlled Trial ◽  
Food And Drug Administration ◽  
Drug Approval ◽  
Cancer Drug ◽  
Drug Label ◽  
Regulatory Pathways ◽  
Randomized Controlled ◽  
Study Characteristics

PurposeModifications in cancer drug indications, dosing, and related toxicities after Food and Drug Administration approval are common. It is unclear whether drug approval without a supporting randomized controlled trial (RCT) influences the probability of such modifications.MethodsWe searched the Drugs@FDA Web site for new drug indications for solid tumors approved between January 2006 and December 2016. Study characteristics, regulatory pathways, and label modifications from approval to October 2017 were collected from drug labels. Label modifications were considered to be major if defined as such in the drug label. Indications approved with and without supporting RCTs were compared using logistic regression. The Benjamini-Hochberg false discovery rate method was used to adjust for multiplicity.ResultsWe identified 59 individual drugs for 109 solid tumor indications. Of these, 17 indications (15.6%) were not supported by an RCT, with no change over time. Indications not supported by RCTs were more likely to require companion diagnostic tests (odds ratio [OR], 3.90; P = .02), to include surrogate end points as primary outcomes (OR, 7.88; P < .001), and to receive breakthrough therapy designation (OR, 7.62; P = .006) or accelerated approval (OR, 17.67; P < .001). Indications not supported by RCTs were associated with significantly higher odds of postapproval modifications in common adverse events (71% v 29%; OR, 5.78; P = .002). A nonsignificantly higher odds of postapproval major modifications in warnings and precautions was also observed (88% v 62%; OR, 4.61; P = .051). Postapproval major modifications in indication and usage, dosing and administration, boxed warnings, and contraindications were comparable in the two groups.ConclusionCancer drug indications not supported initially by RCTs are associated with more postmarketing safety-related label modifications. Health care professionals should be vigilant for unrecognized adverse effects when prescribing drugs approved without a supporting RCT.

scholarly journals US Food and Drug Administration (FDA) Emergency Use Authorization: Glass Half Full or Glass Half Empty?

2020 ◽  
Author(s):  
Roy Guharoy ◽  
Edward P Krenzelok
Keyword(s):  
Randomized Controlled Trial ◽  
Drug Administration ◽  
Controlled Trial ◽  
Food And Drug Administration ◽  
Healthcare Providers ◽  
Efficacy And Safety ◽  
Open Label ◽  
Anecdotal Report ◽  
Randomized Controlled ◽  
The Us

Abstract Recently, the US Food and Drug Administration (FDA) issued emergency use authorization (EUA) for convalescent plasma (CP) for the treatment of hospitalized patients with coronavirus disease 2019 based on a non–peer-reviewed, open-label, observational study. Issuance of an EUA without a proven randomized, controlled trial (RCT) sets a dangerous precedent since the premature action drives healthcare providers and patients away from RCTs that are essential for determining the efficacy and safety of CP. More caution should have been taken based on what was learned from the recent debacle related to the rescinded EUA of hydroxychloroquine and chloroquine, which were approved initially based on an anecdotal report. The FDA process for determining efficacy and safety must be based solely on data from RCTs in order to sustain public and professional trust for future treatment and vaccine efforts to be successful.

Popular diets

2011 ◽  
pp. 213-216
Keyword(s):  
Health Care ◽  
Randomized Controlled Trial ◽  
Health Care Professionals ◽  
Controlled Trial ◽  
Potential Harm ◽  
Randomized Controlled ◽  
Scientific Principles

This section is included to help orientate health-care professionals to diets that their patients may initiate or possibly seek advice about. It does not validate their efficacy. For many, evidence of benefit in the form of a randomized controlled trial is not available. However, the concerns, described below, about potential harm resulting from some diets are based on scientific principles....

Trajectories of Injectable Cancer Drug Costs After Launch in the United States

2018 ◽  
Vol 36 (4) ◽  
pp. 319-325 ◽  
Author(s):  
Noa Gordon ◽  
Salomon M. Stemmer ◽  
Dan Greenberg ◽  
Daniel A. Goldstein
Keyword(s):  
Drug Administration ◽  
Food And Drug Administration ◽  
The United States ◽  
Drug Costs ◽  
Cancer Drug ◽  
Steady Increase ◽  
Drug Prices ◽  
The Us ◽  
The Mean ◽  
Over Time

Purpose Cancer drug prices at launch have increased in recent years. It is unclear how individual drug prices change over time after launch and what market determinants influence these changes. We measured the price trajectories of a cohort of cancer drugs after their launch into the US market and assessed the influence of market structure on price changes. Methods We studied the changes in mean monthly costs for a cohort of 24 patented, injectable anticancer drugs that were approved by the US Food and Drug Administration between 1996 and 2012. To account for discounts and rebates, we used the average sales prices published by the Centers for Medicare and Medicaid Services. Costs were adjusted to US general and health-related inflation rates. For each drug, we calculated the cumulative and annual drug cost changes. We then used a multivariable regression model to evaluate the association between market and cost changes over time. Results With a mean follow-up period of 8 years, the mean percent change in cost for all drugs was +25% (range, −14% to +96%). After adjusting for inflation, the mean cost change was +18% (range, −16% to +59%). Rituximab and trastuzumab followed a similar pattern in cost increases over time, and the inflation-adjusted monthly costs rose since approval by 49% and 44%, respectively. New supplemental US Food and Drug Administration approvals, new off-label indications, and new competitors did not influence the annual cost change rates. Conclusion Anticancer drug costs may change substantially after launch. Regardless of competition or supplemental indications, there is a steady increase in costs of patented anticancer agents over time. New regulations may be needed to prevent additional increases in drug costs after launch.

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