Home > Executive Summaries > Systematic review and cost-effectiveness...

PubMed Health. A service of the National Library of Medicine, National Institutes of Health.

NIHR Health Technology Assessment programme: Executive Summaries. Southampton (UK): NIHR Journals Library; 2003-.

NIHR Health Technology Assessment programme: Executive Summaries.

Systematic review and cost-effectiveness evaluation of 'pill-in-the-pocket' strategy for paroxysmal atrial fibrillation compared to episodic in-hospital treatment or continuous antiarrhythmic drug therapy

C Martin Saborido, J Hockenhull, A Bagust, A Boland, R Dickson, and D Todd.

Author Information

C Martin Saborido,1 J Hockenhull,1 A Bagust,1 A Boland,1 R Dickson,1,* and D Todd2.

1 Liverpool Reviews and Implementation Group (LRiG), Liverpool, UK
2 Liverpool Heart & Chest Hospital, Liverpool, UK
* Corresponding author

Published: 2010.


  1. To summarise the results of the rapid reviews of the clinical effectiveness and cost-effectiveness literature describing the pill-in-the-pocket (PiP) approach for the treatment of patients with paroxysmal atrial fibrillation (PAF).
  2. To develop an economic model to assess the cost-effectiveness of PiP compared with in-hospital treatment (IHT) or continuous antiarrhythmic drugs (AADs) for the treatment of patients with PAF.


Atrial fibrillation (AF) is a tachyarrhythmia characterised by unco-ordinated atrial activation with consequent deterioration of impairment of atrial function and a rapid, irregular heartbeat. The patient may experience palpitations, chest pain, dizziness or, in severe cases, loss of consciousness. In some cases, patients with AF may present without any symptoms. An incidence of AF may be self-terminating or require clinical intervention (for example, pharmacological or medical cardioversion). The annual incidence rate of PAF has been estimated at 1.0 per 1000 person-years (95% confidence interval 0.9 to 1.1), and reported prevalence rates show wide variations depending on age and country.

The classification of AF is called the 3 'P' classification: paroxysmal, persistent and permanent. When a patient experiences two or more AF episodes that terminate within 7 days (usually within 48 hours), AF is classified as paroxysmal. If a patient suffers more than one attack and the AF attack lasts longer than 7 days, the AF is classified as persistent. If the AF episode does not resolve for over a year and/or is not successfully terminated by cardioversion, the pattern is classified as permanent.

Conventional treatment strategies for PAF focus on the suppression of paroxysms of AF and return to normal sinus rhythm (NSR). AAD treatment can consist of (i) continuous prophylactic treatment or (ii) episodic IHT. Prophylactic treatment (daily dose) can include the use of beta-blockers, class Ic agents (e.g. flecainide, propafenone) or class III agents (sotalol, amiodarone). Episodic treatment of PAF consists of pharmacological cardioversion usually involving an intravenous infusion of AADs in a hospital setting or, if this fails, electrical direct current cardioversion.


Electronic searches were conducted to identify clinical effectiveness and cost-effectiveness evidence describing the use of a PiP strategy for the treatment of PAF, published since the release of the Royal College of Physicians' national guidelines on AF in June 2006. An additional search was also undertaken, excluding the term 'pill-in-the-pocket' in order to identify economic evaluations and costing studies describing the comparator treatments to support the development of the economic model.

A Markov model was constructed to examine differences between three PAF strategies (PiP, AAD and IHT) in terms of cost per quality-adjusted life-year (QALY). A Markov model structure was chosen because it is assumed that PAF is a condition that causes patients to move between a limited number of relevant health states during their lives. This type of model allows a large number of cycles to be simulated without having to create a new decision tree in each cycle. The three PAF strategies have the same five health states:

The economic evaluation has been undertaken from an NHS and Personal Social Services perspective. The model has been developed with a cycle length of 1 year and is simulated for the remaining lifetime of all patients.


The search strategies for clinical studies identified 201 randomised controlled trials (RCTs). None of the identified RCTs compared PiP with any other treatment for PAF and therefore did not meet the inclusion criteria for the review. No relevant studies were identified by the search for ongoing trials.

Of the 201 RCTs identified, 12 were deemed to be relevant to the decision problem as they included drugs used to treat PAF; summary data were abstracted from these studies in order to inform the development of the economic model only. The 12 RCTs were all conducted in a hospital setting and prior to the publication of the current national guidelines. One additional study was identified that had informed the evidence considered in Atrial fibrillation: national clinical guideline for management in primary and secondary care developed by the National Collaborating Centre for Chronic Conditions in 2006.

The model results indicate that the PiP strategy is slightly less effective than the other two strategies, but also less costly (incremental cost-effectiveness ratio of £45,916 per QALY when compared to AAD, and £12,424 per QALY when compared to IHT). The one-way sensitivity analyses performed do not show substantial changes in relative cost-effectiveness except in relation to the age of patients, where PiP dominates AAD in men over 65 years and in women over 70 years.

The probabilistic sensitivity analysis demonstrates how close the three strategies are to each other, and the uncertainties in the data. All conclusions need to be considered in relation to these uncertainties.


The systematic review of clinical evidence did not identify any new studies that had not been included in the previously available guidelines.

Overall, a PiP strategy seems to be slightly less effective (i.e. fewer QALYs gained) than AAD and IHT, but is associated with cost savings.

A PiP strategy seems to be more efficacious and cost-effective than an AAD strategy in men over 65 years and women over 70 years, but this is principally due to a very slight difference in QALY gained by the PiP strategy.

A change in clinical practice that includes the introduction of PiP may save costs, but also involves a reduction in clinical effectiveness compared to existing approaches used to treat patients with PAF.

Uncertainty in the available clinical data means there was insufficient evidence to support a recommendation for the use of PiP strategy in patients with PAF. Further research should identify outcomes of interest such as adverse events and recurrent AF episodes in an RCT setting because the only clinical study addressing these issues, even partially, is not an RCT but a descriptive analysis.

Patient preferences also need to be considered in any future research designs.


  • Martin Saborido C, Hockenhull J, Bagust A, Boland A, Dickson R, Todd D. Systematic review and cost-effectiveness evaluation of 'pill-in-the-pocket' strategy for paroxysmal atrial fibrillation compared to episodic in-hospital treatment or continuous antiarrhythmic drug therapy. Health Technol Assess 2010;14(31). [PubMed: 20569652]

NIHR Health Technology Assessment programme

The Health Technology Assessment (HTA) programme, part of the National Institute for Health Research (NIHR), was set up in 1993. It produces high-quality research information on the effectiveness, costs and broader impact of health technologies for those who use, manage and provide care in the NHS. 'Health technologies' are broadly defined as all interventions used to promote health, prevent and treat disease, and improve rehabilitation and long-term care.

The research findings from the HTA programme directly influence decision-making bodies such as the National Institute for Health and Clinical Excellence (NICE) and the National Screening Committee (NSC). HTA findings also help to improve the quality of clinical practice in the NHS indirectly in that they form a key component of the 'National Knowledge Service'.

The HTA programme is needs led in that it fills gaps in the evidence needed by the NHS. There are three routes to the start of projects.

First is the commissioned route. Suggestions for research are actively sought from people working in the NHS, from the public and consumer groups and from professional bodies such as royal colleges and NHS trusts. These suggestions are carefully prioritised by panels of independent experts (including NHS service users). The HTA programme then commissions the research by competitive tender.

Second, the HTA programme provides grants for clinical trials for researchers who identify research questions. These are assessed for importance to patients and the NHS, and scientific rigour.

Third, through its Technology Assessment Report (TAR) call-off contract, the HTA programme commissions bespoke reports, principally for NICE, but also for other policy-makers. TARs bring together evidence on the value of specific technologies.

Some HTA research projects, including TARs, may take only months, others need several years. They can cost from as little as £40,000 to over £1 million, and may involve synthesising existing evidence, undertaking a trial, or other research collecting new data to answer a research problem.

The final reports from HTA projects are peer reviewed by a number of independent expert referees before publication in the widely read journal series Health Technology Assessment.

Criteria for inclusion in the HTA journal series

Reports are published in the HTA journal series if (1) they have resulted from work for the HTA programme, and (2) they are of a sufficiently high scientific quality as assessed by the referees and editors.

Reviews in Health Technology Assessment are termed 'systematic' when the account of the search, appraisal and synthesis methods (to minimise biases and random errors) would, in theory, permit the replication of the review by others.

The research reported in this issue of the journal was commissioned by the HTA programme as project number 08/46/01. The contractual start date was in May 2009. The draft report began editorial review in September 2009 and was accepted for publication in March 2010. As the funder, by devising a commissioning brief, the HTA programme specified the research question and study design.The authors have been wholly responsible for all data collection, analysis and interpretation, and for writing up their work. The HTA editors and publisher have tried to ensure the accuracy of the authors' report and would like to thank the referees for their constructive comments on the draft document. However, they do not accept liability for damages or losses arising from material published in this report.

The views expressed in this publication are those of the authors and not necessarily those of the HTA programme or the Department of Health.

Editor-in-Chief: Professor Tom Walley CBE

Series Editors: Dr Martin Ashton-Key, Dr Aileen Clarke, Professor Chris Hyde, Dr Tom Marshall, Dr John Powell, Dr Rob Riemsma and Professor Ken Stein

© 2010 Crown Copyright.

Included under terms of UK Non-commercial Government License.

PMID: 20569652

PubReader format: click here to try

PubMed Health Blog...

read all...

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...