Off-label drugs in palliative care: a Group Delphi treatment recommendation process

ObjectivesThe use of drugs beyond their marketing authorisation, that is, off-label use, is common practice in palliative care with over 70% of off-label use having little or no scientific support. The lack of evidence makes recommendations for off-label use essential, in order to increase the safety of drug therapy and thus patient safety. The aim of this study was to develop a guide for preparing and consenting drug-specific recommendations for off-label use in palliative care.MethodsGroup Delphi Study with three rounds and a prior online survey to identify topics of dissent. Participants represented professional groups working in palliative care involved in direct patient care and/or drug management and various care settings. Furthermore, representatives of relevant professional associations, experts with academic, non-clinical background and experts with international expertise were invited.Results18/20 invited professionals participated in the prior online-survey. 15 experts participated in the Group Delphi process. Six domains, including identification of drugs, drug uses, assessment of evidence, formulation, consensus and updating of recommendations were generated and respective statements were included in the Group Delphi process. The consensus process resulted in 28 statements forming the guide for recommendations.ConclusionsThe resultant systematic approach for preparing and consenting drug-specific recommendations for off-label use will allow the development of recommendations with transparent and reproducible monographs. This will help to increase treatment quality and patient safety as well as security of decision-making in palliative care. The developed guide is part of a larger project aiming to provide therapy recommendations for areas that have little or no scientific evidence.

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Guide for recommendations on specific drug-related off-label treatment in palliative care: A Group Delphi process

10.21203/rs.2.17086/v1 ◽

2019 ◽

Author(s):

Constanze Remi ◽

Kathrin Weingärtner ◽

Vera Hagemann ◽

Claudia Bausewein ◽

Farina Hodiamont

Keyword(s):

Palliative Care ◽

Patient Safety ◽

Delphi Study ◽

Online Survey ◽

Delphi Process ◽

Treatment Quality ◽

Direct Patient Care ◽

Off Label Use ◽

Off Label ◽

Label Use

Abstract Background The use of drugs beyond their authorisation label, i.e. off-label-use, is common practice in palliative care with over 70% of off-label-use having little or no scientific support. Recommendations for off-label-use are essential to increase the safety of drug therapy and thus patient safety. The aim was to develop a guide for preparing and consenting drug-specific recommendations for off-label-use in palliative medicine.Methods Group Delphi Study with three rounds and a prior online survey. Participants represented professional groups working in palliative care involved in direct patient care and/or drug management (doctors, pharmacists, nurses) and various care settings (inpatient/community, university/non-university). Furthermore, representatives of relevant professional associations, experts with academic, non-clinical background and experts with international expertise were invited.Results For the preliminary online-survey 18/20 invited participants returned 18 questionnaires. Six domains, including identification of drugs, drug uses, assessment of evidence, formulation, consensus and updating of recommendations were generated and eventually 22 statements were included in the Group Delphi process. 15 experts participated in this consensus process. In combination with the survey results, consensus was achieved over a 28 statements after 3 Delphi rounds.Conclusions The resulted systematic approach for preparing and consenting drug-specific recommendations for off-label-use will allow to develop such recommendations with transparent and reproducible monographs. This will help to increase treatment quality and patient safety as well as security of decision-making in palliative care. The developed guide is part of a larger project aiming to provide therapy recommendations for areas that have little or no scientific evidence to date.

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Medicamentos passíveis de infusão por hipodermóclise

Medicina (Ribeirao Preto Online) ◽

10.11606/issn.2176-7262.v51i1p55-68 ◽

2018 ◽

Vol 51 (1) ◽

pp. 55-68

Author(s):

Rita de Cássia Quaglio ◽

Fabiana Rossi Varallo ◽

Nereida Kilza da Costa Lima ◽

André Felipe Junqueira ◽

Edgar Ianhez Júnior ◽

...

Keyword(s):

Palliative Care ◽

Off Label Use ◽

Off Label ◽

Hospice Palliative Care ◽

Care Nursing ◽

Label Use

Modelo do estudo: Revisão Sistemática da Literatura e discussão com profissionais especialistas. Objetivo: Propor a lista de medicações, diluente e volume de diluição, para o uso por hipodermóclise, a pacientes acima de 18 anos Método: Com base em diretrizes Prisma, foi realizado um levantamento bibliográfico na base de dados MEDLINE através do portal Pubmed e pela biblioteca virtual SCIELO, utilizando os descritores: infusions; subcutaneous; palliative care; hospice; palliative care nursing e as palavra-chave hypodermoclysis e off-label use, seus correspondentes em português e seus cruzamentos. Os artigos encontrados foram analisados a partir do instrumento AMSTAR, seguido de discussão com profissionais de formação avançada em CP. Resultados: Dos artigos foram extraídas as seguintes variáveis: medicamentos administrados por hipodermóclise, veículo e volume de diluição, tempo de infusão, forma de administração (continua e em bolus), além de observações referentes à administração em sítio único e concentração máxima. A partir destas variáveis elaborou-se síntese em relação às medicações a serem utilizadas. Conclusões: Chegou-se a uma lista de medicações, dosagem, volume de diluição e diluente. Os resultados encontrados na literatura foram discutidos em processo dialógico e convergente, pelos profissionais de enfermagem, medicina e farmácia. Sendo assim, esta lista possui perfil replicável para outros serviços com cuidados paliativos ou que utilizam a via hipodermóclise.

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Off-Label Use of Drugs in Pain Medicine and Palliative Care: An Algorithm for the Assessment of its Safe and Legal Prescription

Pain Practice ◽

10.1111/j.1533-2500.2008.00189.x ◽

2008 ◽

Vol 8 (3) ◽

pp. 157-163 ◽

Cited By ~ 13

Author(s):

Constans C. A. H. H. V. M. Verhagen ◽

Anne G. H. Niezink ◽

Yvonne Y Engels ◽

Yechiel Y. A. Hekster ◽

Joan J. Doornebal ◽

...

Keyword(s):

Palliative Care ◽

Pain Medicine ◽

Off Label Use ◽

Off Label ◽

Label Use

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Research on patient safety for off-label use of recombinant factor VIIa

American Journal of Health-System Pharmacy ◽

10.2146/ajhp140493 ◽

2015 ◽

Vol 72 (8) ◽

pp. 600-602 ◽

Cited By ~ 1

Author(s):

Agnes E. Aysola ◽

Monika M. Wahi ◽

Russell P. McKelvey ◽

Cynthia Russell Gerdik

Keyword(s):

Patient Safety ◽

Recombinant Factor Viia ◽

Factor Viia ◽

Off Label Use ◽

Off Label ◽

Label Use

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Off-label drug use in home palliative care: A non-evidence-based established practice.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.31_suppl.225 ◽

2017 ◽

Vol 35 (31_suppl) ◽

pp. 225-225

Author(s):

Laura Velutti ◽

Carlotta Pavesi ◽

Diego Lopane ◽

Concetta Arcanà ◽

Annalisa Saetta ◽

...

Keyword(s):

Palliative Care ◽

Retrospective Analysis ◽

Evidence Based ◽

Care Pathways ◽

Administration Route ◽

Off Label Use ◽

Off Label ◽

Treatment Interruptions ◽

Infusion Duration ◽

Label Use

225 Background: Advanced cancer patients (pts) often present with multiple concomitant symptoms and off-label use of drugs (indications doses formulations administration route) is a common practice. Drugs mixture (DM) solutions by continuous administration are frequently used. However, evidence-based data in this setting is scarce. Methods: We performed a retrospective analysis of 576 consecutive care pathways provided by our Home Palliative Care (HC) Service from Jul 2010 to Jun 2017. Infusions were administered subcutaneously (sc) or by a venous (iv) access, by elastomeric pumps (EP) (5 days - 2 mL/h) with drugs diluted in 0.9% NaCl with no light protection. We analyzed: treated symptoms, drugs, doses/concentrations, solution transparency, administration route, infusion duration, clinical response, adverse events (AEs), compliance/treatment acceptability, device proper functioning, and treatment interruptions. Results: We analyzed 266 pts out of 576 care pathways treated with DM infusions, M/F 143/123, median age 70 yrs (21-92); treated symptoms: pain (50%), nausea/vomiting (20%), dyspnea/agitation (20%), dysphagia/mucositis (18%); infused drugs: morphine, midazolam, dexamethasone, ranitidine, metoclopramide, scopolamine, alizapride, haloperidol, furosemide, and ketorolac. Median number of drugs in the DM was 3 (1-6). Administration route was sc in 214 pts/80%, iv in 52 pts/20%. Median infusion duration was 5 days (0-64). Symptoms control was achieved within 72 h in 69% of pts. No AEs related to the infusion devices were observed. Compliance was good in 92% of pts, poor/inadequate in 8%. 5 EP malfunctions were observed: 1 human error, 1 device obstruction due to furosemide flocculation, 3 unexplained. Also, 3 pts required sc infusion interruption due to fluid accumulation near the injection site. Conclusions: This retrospective analysis on a large number of pts shows efficacy and tolerability of DM administration by EP in the HC setting. Treatment compliance was high, no AEs were observed, EP malfunction and therapy discontinuation were rare. However, there are still many open questions about the off-label use of drugs in this setting, and prospective trials are strongly suggested.

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An online survey of Australian physicians reported practice with the off-label use of nebulised frusemide

BMC Palliative Care ◽

10.1186/1472-684x-11-6 ◽

2012 ◽

Vol 11 (1) ◽

Cited By ~ 3

Author(s):

Phillip J Newton ◽

Patricia M Davidson ◽

Christine Sanderson

Keyword(s):

Online Survey ◽

Off Label Use ◽

Off Label ◽

Label Use

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Drug use beyond the licence in palliative care: A systematic review and narrative synthesis

Palliative Medicine ◽

10.1177/0269216319840602 ◽

2019 ◽

Vol 33 (6) ◽

pp. 650-662 ◽

Cited By ~ 5

Author(s):

Vera Hagemann ◽

Claudia Bausewein ◽

Constanze Remi

Keyword(s):

Palliative Care ◽

Clinical Practice ◽

Drug Use ◽

Meta Analysis ◽

Management Strategies ◽

Narrative Synthesis ◽

Off Label Use ◽

Off Label ◽

Study Designs ◽

Label Use

Background: Drug use beyond the licence (off-label use, off-label drug use) is a common practice in palliative care and respective recommendations can often be identified in the literature. It is both risky and offers opportunities at the same time and, therefore, requires special attention in clinical practice. Aim: To determine the prevalence of off-label drug use in palliative care and to identify, evaluate and critically appraise studies describing the clinical practice, healthcare professionals’ awareness, knowledge and attitudes towards off-label-use and management strategies. Design: Systematic literature review following the guidance of the Centre for Reviews and Dissemination. Data sources: Medline, Embase, Web of Science and Current Contents Connect were searched in July 2018 as well as hand searches. The reference lists of pertinent studies were screened for further relevant publications, and citation tracking was performed. Results: Eight studies met the inclusion criteria. Due to the variety in study designs and settings, no meta-analysis or meaningful statistical analysis was possible and a narrative synthesis of the data was performed. Frequency of off-label drug use ranged from 14.5% to 35%. Up to 97% of palliative care units did not have any policy or guidance on handling off-label drug use. About 20% of prescribers never obtain consent in the context of off-label use. Conclusion: Off-label use is common in palliative care with up to one-third of prescriptions affected. Challenges are often related to obtaining informed consent. Little is known about the decision-making process. More information and guidance for the prescribers are needed to enable safe handling of drugs outside their licence in palliative care.

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Off-label use of dexmedetomidine in paediatric anaesthesiology: an international survey of 791 (paediatric) anaesthesiologists

European Journal of Clinical Pharmacology ◽

10.1007/s00228-020-03028-2 ◽

2020 ◽

Author(s):

Camille E. van Hoorn ◽

Robert B. Flint ◽

Justin Skowno ◽

Paul Davies ◽

Thomas Engelhardt ◽

...

Keyword(s):

Online Survey ◽

International Study ◽

Procedural Sedation ◽

Off Label Use ◽

Prescribing Practices ◽

Off Label ◽

The Usa ◽

Paediatric Practice ◽

Icu Sedation ◽

Label Use

Abstract Purpose The purpose of this international study was to investigate prescribing practices of dexmedetomidine by paediatric anaesthesiologists. Methods We performed an online survey on the prescription rate of dexmedetomidine, route of administration and dosage, adverse drug reactions, education on the drug and overall experience. Members of specialist paediatric anaesthesia societies of Europe (ESPA), New Zealand and Australia (SPANZA), Great Britain and Ireland (APAGBI) and the USA (SPA) were consulted. Responses were collected in July and August 2019. Results Data from 791 responders (17% of 5171 invitees) were included in the analyses. Dexmedetomidine was prescribed by 70% of the respondents (ESPA 53%; SPANZA 69%; APAGBI 34% and SPA 96%), mostly for procedural sedation (68%), premedication (46%) and/or ICU sedation (46%). Seventy-three percent had access to local or national protocols, although lack of education was the main reason cited by 26% of the respondents not to prescribe dexmedetomidine. The main difference in dexmedetomidine use concerned the age of patients (SPA primarily < 1 year, others primarily > 1 year). The dosage varied widely ranging from 0.2–5 μg kg−1 for nasal premedication, 0.2–8 μg kg−1 for nasal procedural sedation and 0–4 μg kg−1 intravenously as adjuvant for anaesthesia. Only ESPA members (61%) had noted an adverse drug reaction, namely bradycardia. Conclusion The majority of anaesthesiologists use dexmedetomidine in paediatrics for premedication, procedural sedation, ICU sedation and anaesthesia, despite the off-label use and sparse evidence. The large intercontinental differences in prescribing dexmedetomidine call for consensus and worldwide education on the optimal use in paediatric practice.

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International Survey for Strategies Used for Oral Anticoagulation Reversal in Children

Blood ◽

10.1182/blood-2019-129118 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 4976-4976

Author(s):

Shveta Gupta ◽

Ayesha Zia ◽

Ravindra Sarode

Keyword(s):

Board Of Directors ◽

Vitamin K ◽

Major Bleeding ◽

Online Survey ◽

Pediatric Population ◽

Oral Anticoagulants ◽

Off Label Use ◽

Advisory Committees ◽

Off Label ◽

Label Use

Background: Vitamin K antagonists (VKA) have been the main stay of oral anticoagulation (OAC) in pediatrics. However, VKA have multiple challenges. The pharmacological properties of direct oral anticoagulants (DOACs) suggest that they may have advantages particularly for children. The off-label use of DOACs is however on the rise within the pediatric population. The increasingly broad and varied use of DOACs, lack of published clinical guidance, and limited data on reversal strategies have created the imperative to identify strategies for OAC reversal in pediatrics. We conducted an online survey for strategies used for oral anticoagulants reversal in pediatrics. Study Design: Institutional review board approval was obtained and an online survey was developed using the RedCap. The survey was electronically distributed by International Society of Hemostasis and Thrombosis (ISTH) to its Pediatric/Neonatal Thrombosis and Hemostasis Subcommittee group members. The survey questions asked approach to common hypothetical clinical scenarios for OAC reversal.The data were analysed descriptively. Results: There were 76 respondents, majority from academic free-standing Children'sHospitals. Seventy-two percent reported having a hemostasis-thrombosis/anticoagulation service but only 29 % have a dedicated anticoagulation pharmacist. Approximately 40% do not have a formal protocol in place for VKA reversal. For a supra-therapeutic INR (INR > 5) in a non-bleeding patient, 95% opted to manage by omitting the next dose of VKA while 18 % opted to give oral vitamin K alone or comitantly. For clinically relevant non-major bleeding, majority indicated using Vitamin K; oral (51%) or IV (37). For major bleeding on VKA, majority use either a combination of 4F-PCC and IV Vitamin K or plasma and IV Vitamin K (44/76 and 26/76 respectively). The presence of bleeding seemed to be the major driver for the choice of route (enteral versus parenteral) for Vitamin K for VKA reversal. Thirty-six of the 76 respondents indicated using DOACs; 94% used FXa inhibitors and 1/3 use dabigatran in their clinical practice. For non-urgent DOAC reversal, 97% indicated omitting the next dose. For non-major bleeding on DOAC, majority (29/36) indicated omitting the next dose/doses, some chose 4F-PCC (8/36) and only a few indicated use of specific reversal agents (3/36 and 1/36 for Dabigatran and Andexanet respectively). For major bleeding while on DOACs, the use of specific reversal agents (11/35, 6/35 for Andexanet and idarucizumab respectively) followed by 4F-PCC (9/35) was the major intervention indicated. Dilute thrombin time and partial thromboplastin time were the most commonly utilized tests to measure residual dabigatran activity. For Factor Xa inhibitors routine heparin assay rather than DOAC calibrated anti-Xa activity is utilized by most of the responders to assess presence of the plasma drug activity. Conclusion: Practices for oral anticoagulants reversal vary substantially in the pediatric population. Plasma is still used for urgent VKA reversal in many pediatric centers. The off-label use of DOACs in children is on the rise. Our results highlight the need for further studies to standardize OAC reversal in children. Disclosures Gupta: Novo Nordisk: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda-Shire: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; CSL Behring: Research Funding; Novartis: Honoraria, Speakers Bureau; Octapharma: Honoraria, Membership on an entity's Board of Directors or advisory committees. Sarode:Portola: Honoraria; Octaphrarma: Consultancy; CSL Behring: Consultancy; Siemens: Research Funding. OffLabel Disclosure: The pharmacological properties of direct oral anticoagulants (DOACs) suggest that they may have advantages particularly for children. They are currently not approved in children. The off-label use of DOACs is however on the rise within the pediatric population.

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