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Keele’s ‘Important News and Evidence’ Service
KINES
Rapid Update
April 2016
Safer Prescribing: A Trial of Education, Informatics, and Financial Incentives
High-risk prescribing and preventable drug-related complications are common in primary care in the UK. The DataDriven Quality Improvement in Primary Care Programme (DQIP) study from Scotland evaluated whether the rates of
high-risk prescribing by general practitioners (GPs) and associated hospitalisations could be reduced by a complex
intervention. This comprised professional education; use of information from GP computer systems to facilitate review;
and financial incentives for practices to review individual patients’ medical records to assess prescribing
appropriateness. The study concluded that this intervention reduced the rate of high-risk prescribing of antiplatelet
medications and nonsteroidal anti-inflammatory drugs (NSAIDs), and may have improved clinical outcomes by
reducing relevant hospital admissions.
Dreischulte T, Donnan P, Grant A, Hapca A, McCowan C, and Guthrie B. Safer Prescribing — A Trial of Education,
Informatics, and Financial Incentives. N Engl J Med 2016; 374:1053-1064.
What do we know already?
An important study conducted in Liverpool hospitals between 2001 and 2002 found that 6.5% of acute hospital
admissions could be attributed to adverse drug reactions. The main drugs responsible for these admissions were:
aspirin and NSAIDs (30%), diuretics (27%), warfarin (11%), and ACEIs (8%). It was estimated that 72% of these
admissions were avoidable. Obviously these are old data but there is little indication that improvements have been
made since that time.
Prescribing (un)safety indicators have been developed to identify patients in general practice at increased risk of
hazardous prescribing. Some of these increased risks could result in acute admissions. See the discussion of the
development of these indicators by Avery et al, 2014.
The use of such indicators as a focus for educational interventions by clinical pharmacists was explored in the
PINCER trial. This was a cluster randomised study in England involving 72 practices which showed that the
pharmacist-led intervention reduced the frequency of unsafe indicators (‘the PINCER set’) in general practice. At 6
months' follow-up, patients in the PINCER group were significantly less likely to have been prescribed a nonselective NSAID if they had a history of peptic ulcer without gastroprotection; a β blocker if they had asthma; or an
ACE inhibitor or loop diuretic without appropriate monitoring (these were the primary outcomes).
A recent KINES looked at a study in the BMJ which examined prescribing safety in UK general practice. This study
analysed the records of almost five million patients on the UK Clinical Practice Research Datalink (CPRD) using
previously validated indicators of prescribing safety (developed from and similar to ‘the PINCER set’). Over 5% of
those ‘at risk’ were deemed to have received potentially unsafe prescriptions. Around 12% with an indicator for the
need for blood testing had potential monitoring errors. There was a wide variation between practices.
What does this evidence add?
This study highlights the continuing need to address potential unsafe prescribing in general practice.
The findings from DQIP should be used to encourage the use of computer searches in general practice for unsafe
prescribing as standard practice (for example, using the PINCER audit tool).
Audits of unsafe prescribing should be considered an important or necessary component of GP annual appraisal.
This study shows how informatics can be used to inform this activity.
The reduction in admissions potentially related to prescribing – gastrointestinal events from NSAIDs, and heart
failure events – is impressive and encouraging. There are some weaknesses in trial design that might contribute
to these, such as secular changes, but overall this provides the evidence required to concentrate efforts in general
practice on similar initiatives to reduce harm.
KINES is produced by The Centre for Medicines Optimisation at Keele University for subscriber CCGs. The views expressed are Keele’s and may not reflect local prescribing guidance.
External hyperlinks are provided as a convenience but are out of Keele’s control and do not constitute an endorsement by Keele.
The study reinforces the important role of clinical pharmacists in primary care and can be used to guide a
programme for this work, in line with current NHS England priorities.
DQIP used a complex intervention and it was not possible to determine which element caused most change. It fits
with evidence around changing clinical practice that suggests this needs a multifaceted approach. The component
of the study using financial incentives gives some support for the widespread use of prescribing incentive
schemes in the UK.
The study further encourages educational initiatives and emphasises the place of educational outreach, similar to
that available via IMPACT provided by the Centre for Medicines Optimisation at Keele.
Study details
Participants:
The study recruited 34 GP practices in Tayside, Scotland (66 practices in Tayside were initially approached). 33
practices completed the study.
It was a cluster-randomized, stepped-wedge trial conducted in Tayside, Scotland.
Data were analysed for 33,334 patients in the practices at risk at one or more points in the pre-intervention period
and for 33,060 at risk at one or more points in the intervention period.
Intervention and Comparison
Practices were randomly assigned to various start dates for a 48-week intervention. The trial was randomised by
start date, not intervention (it was a comparison of before and after).
The DQIP intervention included:
o professional education about the risks of NSAIDs and antiplatelets conducted by a visiting pharmacist
(outreach)
o use of additional written material and newsletters
o the use of a data extraction informatics tool to identify patients at high risk of adverse drug reactions related to
NSAIDs, aspirin and clopidogrel. This enabled graphical display of relevant information with weekly updates
and progress reports via a web-based tool.
o structured financial incentives to review patients (which equated to an average overall payment of £550 per
doctor)
The primary outcome was patient-level exposure to any of nine measures of high-risk prescribing of NSAIDs or
selected antiplatelet agents (e.g., NSAID prescription in a patient with chronic kidney disease or co-prescription of
an NSAID and an oral anticoagulant without gastroprotection).
Prespecified secondary outcomes included the incidence of related hospital admissions.
Analyses were performed according to the intention-to-treat principle, with the use of mixed-effect models to
account for clustering in the data.
Outcomes and results
 Targeted high-risk prescribing was significantly reduced from a rate of 3.7% (1,102 of 29,537 patients at risk)
immediately before the intervention to 2.2% (674 of 30,187) at the end of the intervention (adjusted odds ratio,
0.63; 95% confidence interval [CI], 0.57 to 0.68; p<0.001).
 The rate of hospital admissions for:
o gastrointestinal ulcer or bleeding was significantly reduced from the pre-intervention period to the intervention
period (from 55.7 to 37.0 admissions per 10,000 person-years; rate ratio, 0.66; 95% CI, 0.51 to 0.86; p=0.002)
o heart failure was significantly reduced (from 707.7 to 513.5 admissions per 10,000 person-years; rate ratio,
0.73; 95% CI, 0.56 to 0.95; p=0.02)
o acute kidney injury were not significantly reduced (101.9 and 86.0 admissions per 10,000 person-years,
respectively; rate ratio, 0.84; 95% CI, 0.68 to 1.09; p=0.19).
Level of Evidence:
Level 2 (limited quality patient-oriented evidence) according to the SORT criteria.
Study Funding
Funded by the Scottish Government Chief Scientist Office. It was not commercially funded.