Did the Temporary Shortage in Supply of Imiglucerase Have Clinical Consequences? Retrospective Observational Study on 34 Italian Gaucher Type I Patients

Regulatory and clinical consequences of negative confirmatory trials of accelerated approval cancer drugs: retrospective observational study

BMJ ◽

10.1136/bmj.n1959 ◽

2021 ◽

pp. n1959 ◽

Cited By ~ 1

Author(s):

Bishal Gyawali ◽

Benjamin N Rome ◽

Aaron S Kesselheim

Keyword(s):

Observational Study ◽

Primary Endpoint ◽

Clinical Guidelines ◽

Treatment Guidelines ◽

Retrospective Observational Study ◽

Cancer Drug ◽

Cancer Drugs ◽

Nccn Guidelines ◽

Clinical Consequences ◽

Accelerated Approval

Abstract Objectives To investigate the regulatory handling of cancer drugs that were granted accelerated approval by the US Food and Drug Administration (FDA) but failed to improve the primary endpoint in post-approval trials and to evaluate the extent to which negative post-approval trials changed the recommendations in treatment guidelines. Design Retrospective observational study. Setting FDA and National Comprehensive Cancer Network (NCCN) reports. Included drugs Cancer drugs that received accelerated approval from the FDA and had negative post-approval trials. Main outcome measures Regulatory outcomes, including withdrawal, conversion to regular approval, and no action. Results 18 indications for 10 cancer drugs that received accelerated approval but failed to improve the primary endpoint in post-approval trials were identified. Of these, 11 (61%) were voluntarily withdrawn by the manufacturer and one (bevacizumab for breast cancer) was revoked by the FDA. Of the 11 withdrawals, six occurred in 2021 alone. The remaining six (33%) indications remain on the label. The NCCN guidelines provide a high level of endorsement (category 1 endorsement for one and category 2A endorsement for seven) for accelerated approval drugs that have failed post-approval trials, sometimes even after the approval has been withdrawn or revoked. Conclusion Cancer drug indications that received accelerated approval often remained on formal FDA approved drug labelling and continued to be recommended in clinical guidelines several years after statutorily required post-approval trials showed no improvement in the primary efficacy endpoint. Clinical guidelines should better align with the results of post-approval trials of cancer drugs that received accelerated approval.

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A hospital based plain radiographic observational study of lumbosacral transitional vertebrae in the Nepalese population

Asian Journal of Medical Sciences ◽

10.3126/ajms.v9i4.19725 ◽

2018 ◽

Vol 9 (4) ◽

pp. 46-50

Author(s):

Manoj Bhattarai

Keyword(s):

Observational Study ◽

Lumbosacral Spine ◽

Type I ◽

Cross Sectional ◽

Transitional Vertebra ◽

Type Iv ◽

Wide Range ◽

Clinical Consequences ◽

Lumbosacral Transitional Vertebra ◽

Lumbosacral Transitional Vertebrae

Background: Presence of lumbosacral transitional vertebra may lead to number of clinical consequences because of failure to correctly number the problematic vertebra and also has been associated with low back pain. Different studies done at different part of the world have shown wide range of prevalence of lumbosacral transitional vertebra.Aims and Objective: This hospital based cross sectional observational study was undertaken to determine the prevalence of lumbosacral transitional vertebra among the Nepalese population.Materials and Methods: Plain radiographs (anteroposterior and lateral views of lumbosacral spine and KUB radiographs) of 947 patients (646 with lumbosacral spine and 301 with KUB radiographs) done from August 2015 to July 2016 and meeting inclusion criteria were retrospectively analyzed for the presence of lumbosacral transitional vertebra.Results: The overall prevalence of lumbosacral transitional vertebra was 14.7% with prevalence of 16.3% in patients with lumbosacral radiographs and 11.3% in patients with KUB radiographs and was statistically significant. Prevalence of sacralization was higher than lumbarization (11.9% Vs 2.7%). Lumbosacral transitional vertebra was more common in females than in males with Castellvi type I being most common and type IV least common.Conclusion: The overall prevalence of lumbosacral transitional vertebra in the studied Nepalese population was 14.7% with significantly higher prevalence in patients with lumbosacral radiographs than with KUB radiographs.Asian Journal of Medical Sciences Vol.9(4) 2018 46-50

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Hemmkörperentwicklung bei Hämophilie-Patienten nach Präparate wechsel

Hämostaseologie ◽

10.1055/s-0037-1619773 ◽

2012 ◽

Vol 32 (S 01) ◽

pp. S39-S42 ◽

Cited By ~ 1

Author(s):

S. Kocher ◽

G. Asmelash ◽

V. Makki ◽

S. Müller ◽

S. Krekeler ◽

...

Keyword(s):

Risk Factors ◽

Risk Factor ◽

Observational Study ◽

Retrospective Observational Study ◽

Frequent Change ◽

Patient Age ◽

Treatment Regimens ◽

Patient Âgé ◽

The Relationship ◽

Observation Period

SummaryThe retrospective observational study surveys the relationship between development of inhibitors in the treatment of haemophilia patients and risk factors such as changing FVIII products. A total of 119 patients were included in this study, 198 changes of FVIII products were evaluated. Results: During the observation period of 12 months none of the patients developed an inhibitor, which was temporally associated with a change of FVIII products. A frequent change of FVIII products didn’t lead to an increase in inhibitor risk. The change between plasmatic and recombinant preparations could not be confirmed as a risk factor. Furthermore, no correlation between treatment regimens, severity, patient age and comorbidities of the patients could be found.

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