An international initiative to create a collaborative for pharmacovigilance in hospice and palliative care clinical practice

Background: Medication registration currently requires evidence of safety and efficacy from adequately powered phase 3 studies. Pharmacovigilance (phase 4 studies, postmarketing data, adverse drug reaction reporting) provide data on more widespread and longer term use. Historically, voluntary reporting systems for pharmacovigilance have had low reporting rates, relying on ad hoc reporting and retrospective chart reviews, or prospective registries have often been limited to specific drugs or clinical conditions. Furthermore, these data are often irrelevant in hospice and palliative care due to the timeliness of which such data become available and the unique characteristics of our population and prescribing: compounding comorbidities, progressive organ failure, accumulation of symptom-specific medications, tendency to attribute toxicity to disease progression, use of old, off-patent medications, and incorporation of evolving evidence. There is a need for prospective, systematic pharmacovigilance in hospice and palliative care. Method: Here we describe an international, Web-based, 128-bit secure initiative to collect pharmacovigilance data documenting net clinical benefit and safety of common medications. The intention is for a diverse and large group of clinical units to record data prospectively on a small deidentified consecutive cohort of patients started on the medication of interest. A new medication would be studied every 3 months. Three key time points (different for each medication) will be assessed for each patient, collecting easily codefiable data at baseline, a point at which clinical benefit should be experienced, and a point at which short- to medium-term toxicities may occur. Toxicities can additionally be recorded at any time they occur. Data collection will take a maximum of 10 minutes per patient. Conclusion: The intention is to create an efficient, relevant system to improve hospice and palliative care with maximally generalizable results

Off-label prescribing in palliative care – a cross-sectional national survey of Palliative Medicine doctors

Background: Regulatory bodies including the European Medicines Agency register medications (formulation, route of administration) for specific clinical indications. Once registered, prescription is at clinicians’ discretion. Off-label use is beyond the registered use. While off-label prescribing may, at times, be appropriate, efficacy and toxicity data are often lacking. Aim: The aim of this study was to document off-label use policies (including disclosure and consent) in Australian palliative care units and current practices by palliative care clinicians. Design: A national, cross-sectional survey was conducted online following an invitation letter. The survey asked clinicians their most frequent off-label medication/indication dyads and unit policies. Dyads were classified into unregistered, off-label and on-label, and for the latter, whether medications were nationally subsidised. Setting/participants: All Australian palliative medicine Fellows and advanced trainees. Results: Overall, 105 clinicians responded (53% response rate). The majority did not have policies on off-label medications, and documented consent rarely. In all, 236 medication/indication dyads for 36 medications were noted: 45 dyads (19%) were for two unregistered medications, 118 dyads (50%) were for 26 off-label medications and 73 dyads (31%) were for 12 on-label medications. Conclusions: Off-label prescribing with its clinical, legal and ethical implications is common yet poorly recognised by clinicians. A distinction needs to be made between where quality evidence exists but registration has not been updated by the pharmaceutical sponsor and the evidence has not been generated. Further research is required to quantify any iatrogenic harm from off-label prescribing in palliative care

The Prospective Evaluation of the Net Effect of Red Blood Cell Transfusions in Routine Provision of Palliative Care.

"Final publication is available from Mary Ann Liebert, Inc., publishers http://dx.doi.org/10.1089/jpm.2017.0072” This author accepted manuscript is made available following 12 month embargo from date of publication (June 2017) in accordance with the publisher’s archiving policyBackground Red Blood Cell (RBC) transfusions are commonly used in palliative care. RBCs are a finite resource, transfusions carry risks, and the net effect (benefits and harms) is poorly defined for people with life-limiting illnesses. Aim The aim of this study was to examine the indications and the effects of RBC transfusion in palliative care patients. Design This international, multisite, prospective consecutive cohort study assessed target symptoms (fatigue, breathlessness, generalised weakness, or dizziness) prior to transfusion and at day 7 by treating clinicians, using National Cancer Institute Common Terminology Criteria for Adverse Events. Assessment of harms was made at day 2. Setting/participants One-hundred and one transfusions with day 7 followup were collected. Median age was 72·0 (IQR 61·5-83·0) years, 58% male, and mean Australian-modified Karnofsky Performance Status of 48 (SD 17). Results A mean 2·1 (SD 0·6) units was transfused. The target symptom was fatigue (61%), breathlessness (16%), generalized weakness (12%), dizziness (6%) or other (5%). Forty-nine percent of transfusions improved the primary target symptom, and 78% of transfusions improved at least one of the target symptoms. Harms were infrequent and mild. An AKPS of 40-50% was associated with higher chances of symptomatic benefit in the target symptom, however no other predictors of response were identified. Conclusions In the largest prospective consecutive case series to date, clinicians generally reported benefit, with minimal harms. Ongoing work is required to define the optimal patient- and clinician-reported haematological and functional outcome measures to optimise the use of donor blood and minimise transfusion-associated risk

Promoting better use of the PSA test in general practice: randomized controlled trial of educational strategies based on outreach visits and mailout

GREAT CLARENDON ST, OXFORD, ENGLAND, OX2 6D