Contrasting evidence to reimbursement reality for off-label use (OLU) of drug treatments in cancer care: rationale and design of the CEIT-OLU project

BackgroundOff-label use (OLU) of a drug reflects a perceived unmet medical need, which is common in oncology. Cancer drugs are often highly expensive and their reimbursement is a challenge for many healthcare systems. OLU is frequently regulated by reimbursement restrictions. For evidence-based healthcare, treatment ought to be reimbursed if there is sufficient clinical evidence for treatment benefit independently of patient factors not related to the treatment indication. However, little is known about the reality of OLU reimbursement and its association with the underlying clinical evidence. Here, we aim to investigate the relationship of reimbursement decisions with the underlying clinical evidence.Methods/ designWe will extract patient characteristics and details on treatment and reimbursement of cancer drugs from over 3000 patients treated in three Swiss hospitals. We will systematically search for clinical trial evidence on benefits associated with OLU in the most common indications. We will describe the prevalence of OLU in Switzerland and its reimbursement in cancer care, and use multivariable logistic regression techniques to investigate the association of approval/rejection of a reimbursement requests to the evidence on treatment effects and to further factors, including type of drug, molecular predictive markers and the health insurer.DiscussionOur study will provide a systematic overview and assessment of OLU and its reimbursement reality in Switzerland. We may provide a better understanding of the access to cancer care that is regulated by health insurers and we hope to identify factors that determine the level of evidence-based cancer care in a highly diverse western healthcare system.

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Contrasting Evidence to Reimbursement Reality for Off-label use (OLU) of Drug Treatments in Cancer Care – Rationale and Design of the CEIT-OLU-project

10.1101/19003152 ◽

2019 ◽

Author(s):

AK Herbrand ◽

AM Schmitt ◽

M Briel ◽

S Diem ◽

H Ewald ◽

...

Keyword(s):

Health Care ◽

Cancer Care ◽

Clinical Evidence ◽

Health Care Systems ◽

Patient Characteristics ◽

Evidence Based ◽

Cancer Drugs ◽

Level Of Evidence ◽

Treatment Benefit ◽

Off Label

AbstractBackgroundOff-label drug use (OLU) reflects a perceived unmet medical need, which is common in oncology. Cancer drugs are often highly expensive and their reimbursement is a challenge for many health care systems. OLU is frequently regulated by reimbursement restrictions. For evidence-based health care, treatment ought to be reimbursed if there is sufficient clinical evidence for treatment benefit independently of patient factors not related to the treatment indication. However, little is known about the reality of OLU reimbursement and its association with the underlying clinical evidence. Here we aim to investigate the relationship of reimbursement decisions with the underlying clinical evidence.Methods/DesignWe extract patient characteristics and details on treatment and reimbursement of cancer drugs from over 3000 patients treated in three Swiss hospitals. We systematically search for clinical trial evidence on benefits associated with OLU in the most common indications. We will describe the prevalence of OLU in Switzerland and its reimbursement in cancer care, and use multivariable logistic regression techniques to investigate the association of approval/rejection of a reimbursement requests to the evidence on treatment effects and to further factors, including type of drug, molecular predictive markers and the health insurer.DiscussionOur study will provide a systematic overview and assessment of OLU and its reimbursement reality in Switzerland. We may provide a better understanding of the access to cancer care that is regulated by health insurers and we hope to identify factors that determine the level of evidence-based cancer care in a highly diverse Western health care system.

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Medication Repurposing in Pediatric Patients: Teaching Old Drugs New Tricks

The Journal of Pediatric Pharmacology and Therapeutics ◽

10.5863/1551-6776-21.1.36 ◽

2016 ◽

Vol 21 (1) ◽

pp. 36-53 ◽

Cited By ~ 2

Author(s):

Martha M. Rumore

Keyword(s):

New York ◽

Pediatric Patients ◽

Drug Repurposing ◽

Evidence Based ◽

Off Label Use ◽

Level Of Evidence ◽

Off Label ◽

Pediatric Age Group ◽

Evidence Quality ◽

Label Use

OBJECTIVES: Gaps in pediatric therapeutics often result in off-label use and specifically, novel uses for existing medications, termed “drug repurposing.” Drug Information (DI) queries to a Pediatric Medication Resource Center of a large metropolitan pediatric hospital in New York and inherent difficulties in retrieving evidence-based information prompted a review of current medication repurposing for pediatric patients. The objective included characterization of innovative off-label use of medications Food and Drug Administration (FDA)-approved for 1 or more indications to treat a totally different disorder or indication in pediatric patients. METHODS: A systematic literature review was conducted to retrieve publications describing repurposed medications in pediatric patients. Excluded was FDA-approved indications used off-label in pediatric patients (e.g., different dose), preclinical data, adult use only, and experimental use. Evidence quality was classified using a modified American Academy of Neurology Level of Evidence. Results were analyzed using χ2 at p < 0.05. RESULTS: Over 2000 references were retrieved and reviewed. A total of 101 medications repurposed for novel off-label uses for pediatric patients were identified: 38 for neonates, 74 for children, and 52 for adolescents. Neonates and infants were least likely to receive a medication for a repurposed use. Strong or intermediate evidence existed in 80.2% of cases. The evidence was weak in 19.8%. No significant relationship was observed between the pediatric age group and strength of the literature. Most repurposed uses pertained to generic or widely used medications. Less than 5% of medications were first marketed after 2011. CONCLUSIONS: While not exhaustive, the present study represents the most comprehensive listing of novel uses exclusive to pediatric patients. Further research is needed to identify the frequency of repurposed uses. The valuable DI role of pharmacists in assessing repurposed uses is of expanding and increasing importance to ensure such uses are evidence-based.

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Apixaban for Stroke Prevention in Atrial Fibrillation: Why are Event Rates Higher in Clinical Practice than in Randomized Trials?—A Systematic Review

Thrombosis and Haemostasis ◽

10.1055/s-0040-1713889 ◽

2020 ◽

Vol 120 (09) ◽

pp. 1323-1329 ◽

Cited By ~ 1

Author(s):

Tim A. C. de Vries ◽

Jack Hirsh ◽

Ke Xu ◽

Imaad Mallick ◽

Vinai C. Bhagirath ◽

...

Keyword(s):

Systematic Review ◽

Clinical Practice ◽

Thromboembolic Event ◽

Meta Analysis ◽

Patient Characteristics ◽

Thromboembolic Events ◽

Off Label Use ◽

Off Label ◽

Event Rates ◽

Label Use

Abstract Background Recent reports suggest an important contribution from frequent off-label use of apixaban 2.5 mg twice daily to the higher rates of thromboembolic events observed in observational studies (OSs) relative to in randomized controlled trials (RCTs), and consequently, advocate against such use in all patients. Objectives To examine factors contributing to the higher thromboembolic event rates, we estimated the prevalence of off-label use in contemporary practice, and compared patient characteristics and rates of stroke/systemic embolism, major bleeding, and mortality by apixaban dose and by study design in a systematic review and meta-analysis. Results and Discussion We identified 18 OSs and 2 RCTs that included 155,228 and 11,928 patients, respectively. Patients in OSs more often received apixaban 2.5 mg twice daily (31.3% vs. 5.1%), were older (mean age 73.8 vs. 69.8 years), and had higher CHA2DS2-VASc scores (mean 3.6 vs. 2.9) versus those in RCTs. We observed a consistent pattern of higher rates of thromboembolic events, bleeding, and mortality in patients treated with 2.5 versus 5 mg twice daily apixaban in both OSs and RCTs. Conclusion The higher risk profiles of patients in OSs versus RCTs, and higher rates of both bleeding and mortality not attributable to thromboembolism in patients treated with apixaban 2.5 versus 5 mg twice daily suggest that differences in patient characteristics are additional important contributors to the higher than expected thromboembolic event rates in clinical practice.

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