An Evidence-Based Review of Off-Label Uses of Polidocanol

Gadolinium-based contrast agents (GBCAs) have been suggested as off-label alternatives to iodine-based contrast agents for fluoroscopic imaging during interventional pain procedures. We report a case of accidental intrathecal administration of a GBCA during a neuraxial interventional pain procedure leading to acute gadolinium neurotoxicity, which resulted in encephalopathy and ultimately death. To our knowledge, it is the first published case of fatal intrathecal gadolinium-induced encephalopathy and the first published case of intrathecal gadoteridol causing serious neurologic complications. In addition, the case presented here is placed in context with an associated comprehensive, evidence-based review of the use of gadolinium in interventional pain procedures, addressing gadolinium chemistry and pharmacologic properties, neurotoxicity and radiology. Physicians must be aware that gadolinium poses a significant risk of acute neurotoxicity even in small doses. Until further safety research is performed, GBCAs should not be considered a safe alternative for use in neuraxial interventional spine procedures when there is a risk of inadvertent intrathecal administration.

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Developing a paediatric drug formulary for the Netherlands

Archives of Disease in Childhood ◽

10.1136/archdischild-2016-311674 ◽

2016 ◽

Vol 102 (4) ◽

pp. 357-361 ◽

Cited By ~ 28

Author(s):

Tjitske M van der Zanden ◽

Saskia N de Wildt ◽

Yves Liem ◽

Martin Offringa ◽

Matthijs de Hoog

Keyword(s):

Drug Therapy ◽

Drug Use ◽

The Netherlands ◽

Evidence Based ◽

Drug Formulary ◽

Concerted Effort ◽

Off Label ◽

Registration Data ◽

Current Content ◽

Professional Guidelines

As many drugs in paediatrics are used off-label, prescribers face a lack of evidence-based dosing guidelines. A Dutch framework was developed to provide dosing guidelines based on best available evidence from registration data, investigator-initiated research, professional guidelines, clinical experience and consensus. This has clarified the scientific grounds of drug use for children and encouraged uniformity in prescribing habits in the Netherlands. The developed framework and the current content of the Dutch Paediatric Formulary could be used as basis for similar initiatives worldwide, preferably in a concerted effort to ultimately provide children with effective and safe drug therapy.

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The Limitations of FDA Criteria: Inconsistencies with Clinical Practice, Findings, and Adult Criteria as a Barrier to Pediatric Implantation

Seminars in Hearing ◽

10.1055/s-0041-1739370 ◽

2021 ◽

Vol 42 (04) ◽

pp. 373-380

Author(s):

Lisa R. Park ◽

Erika B. Gagnon ◽

Kevin D. Brown

Keyword(s):

Clinical Practice ◽

Cochlear Implant ◽

Cochlear Implants ◽

Cochlear Implantation ◽

Spoken Language ◽

Evidence Based ◽

Residual Hearing ◽

Off Label ◽

Single Side ◽

Hearing Children

AbstractChildren require greater access to sound than adults as they are learning to communicate using hearing and spoken language. Yet when it comes to cochlear implant candidacy, currently approved Food and Drug Administration (FDA) criteria for adults are much less restrictive than those for children, allowing for greater levels of residual hearing and aided speech recognition in adults. Cochlear implant guidelines for children have changed very little in the 30 years since cochlear implants have been approved for pediatrics, and this lack of change has proven to be a barrier to implantation. Using evidence-based practice, centers have been providing off-label implantation for children who fall outside of current FDA criteria, including children with more residual hearing, children with single-side deafness younger than 5 years, and infants with bilateral profound loss younger than 9 months. The purpose of this article is to outline how these restrictions impede access to implants for children and describe the evidence supporting cochlear implantation in children who fall outside of current criteria.

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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

ESMO Open ◽

10.1136/esmoopen-2019-000596 ◽

2019 ◽

Vol 4 (6) ◽

pp. e000596

Author(s):

Amanda Katherina Herbrand ◽

Andreas Michael Schmitt ◽

Matthias Briel ◽

Stefan Diem ◽

Hannah Ewald ◽

...

Keyword(s):

Cancer Care ◽

Clinical Evidence ◽

Patient Characteristics ◽

Evidence Based ◽

Cancer Drugs ◽

Off Label Use ◽

Level Of Evidence ◽

Treatment Benefit ◽

Off Label ◽

Label Use

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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Practice insights on patient care—management overview for chemoradiation toxic mucositis—guidelines, guideline-supported therapies and high potency polymerized cross-linked sucralfate (ProThelial)

Journal of Oncology Pharmacy Practice ◽

10.1177/1078155218758864 ◽

2018 ◽

Vol 25 (2) ◽

pp. 409-422 ◽

Cited By ~ 2

Author(s):

Ricky W McCullough

Keyword(s):

Care Management ◽

Healthcare Research ◽

Evidence Based ◽

Symptom Presentation ◽

High Potency ◽

Additional Measure ◽

Supportive Cancer Care ◽

Off Label ◽

High Quality Evidence ◽

Based Medicine

Aim To offer a practice insight for the management of chemoradiation toxic mucositis. Method Review chemoradiation toxic mucositis, its pathobiology and breadth of symptom presentation. Review mucositis guidelines and guideline-supported anti-mucositis therapies. Offer guidance on guidelines and an abbreviated review of high potency cross-linked sucralfate for management of chemoradiation toxic mucositis. Result There are six major mucositis guidelines but only one that is current and regularly updated. Guidelines from the Multinational Association Supportive Cancer Care suggest 14 interventions gleaned from controlled trials, 12 of which are off-label uses of therapies that offer statistically significant but incrementally beneficial outcomes. Several evidence-based limitations of guidelines are discussed. Data on high potency polymerized cross-linked sucralfate confirming complete prevention and rapid (2–3 days) elimination, sustained throughout cancer treatment is verified as high quality evidence in accordance to standards adopted by Agency for Healthcare Research and Quality. A 96–97% reduction in mucositis duration qualifies as a positive Glasziou treatment effect, which is discussed as an additional measure of evidence-based medicine. Conclusion Statistically significant but fractional treatment effects of guideline-supported interventions are not likely to substantially alter the course of mucositis when it occurs nor completely prevent its onset. Complete prevention and rapid sustained elimination should be the goal, therefore high potency polymerized cross-linked sucralfate may be useful. Where guidelines fail, institution-based protocols led by oncology pharmacists could succeed. In an effort to eliminate toxic mucositis, enhance compliance to chemoradiation regimens, and improve survival, such protocols for practice may verify pharmacoeconomic benefits, if any, in using high potency polymerized cross-linked sucralfate to manage toxic mucositis.

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CEUS Guidelines: Evidence Based Medicine or off Label Use?

Ultrasound in Medicine & Biology ◽

10.1016/j.ultrasmedbio.2017.08.1059 ◽

2017 ◽

Vol 43 ◽

pp. S34

Author(s):

Christian Pállson Nolsøe

Keyword(s):

Evidence Based Medicine ◽

Evidence Based ◽

Off Label Use ◽

Off Label ◽

Based Medicine ◽

Label Use

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Off-Label Uses of Topical Vitamin D in Dermatology: A Systematic Review

Journal of Cutaneous Medicine and Surgery ◽

10.2310/7750.2013.13109 ◽

2014 ◽

Vol 18 (2) ◽

pp. 91-108 ◽

Cited By ~ 8

Author(s):

Heidi Wat ◽

Marlene Dytoc

Keyword(s):

Vitamin D ◽

Seborrheic Dermatitis ◽

Evidence Based ◽

Seborrheic Keratosis ◽

Level Of Evidence ◽

Prurigo Nodularis ◽

Off Label ◽

Vitamin D Analogues ◽

Dermatologic Disease ◽

Evidence Based Guidelines

Background:Topical vitamin D is approved by the US Food and Drug Administration for the treatment of psoriasis but is also used off-label in the treatment of a variety of cutaneous diseases despite a lack of evidence-based guidelines.Objective:The objective of this study was to provide evidence-based clinical guidelines for the off-label use of topical vitamin D in the treatment of dermatologic disease.Methods:A systematic literature review was conducted via the MEDLINE, Embase, and CENTRAL databases for off-label uses of topical vitamin D analogues in the treatment of dermatologic disease other than psoriasis. The data were synthesized, and evidence-based recommendations were rendered according to the highest level of evidence available.Results:A total of 165 articles met the inclusion criteria. A moderate to strong recommendation was given for the use of topical vitamin D in combination with corticosteroids and phototherapy in vitiligo and as monotherapy for various ichthyoses, morphea, pityriasis alba, prurigo nodularis, and polymorphous light eruption. There is evidence showing that topical vitamin D is ineffective in the treatment of actinic keratosis, seborrheic keratosis, lichen planus, seborrheic dermatitis, alopecia areata, chemotherapy-induced alopecia, and hypertrophic scars.Conclusion:Topical vitamin D analogues have an important role in the off-label treatment of dermatologic disease, but higher quality studies are still required.

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