Evidence of research activity following asthma treatment uncertainty priority setting exercise in 2007

Research activity following Asthma Treatment Uncertainty Priority Setting
Exercise in 2007 – paper updated January 2010
This paper captures relevant research activity following the completion of JLA priority setting exercise. The activity may range from uncertainties being submitted to commissioning research programmes, to partner organisation’s own research and Priorities for research
1 (a) What are the adverse effects associated with long-term use of short and long-acting bronchodilators; inhaled and oral steroids; and combination and additive therapies in adults? (N.B this includes children aged 12 years old and over) 1 (b) What are the adverse effects associated with long-term use of short and long-acting bronchodilators; inhaled and oral steroids; and combination and additive therapies in children? 2. What is the most effective way of managing asthma with other health problems? 3. What are the key components of successful "Self- Management" for a person with asthma? 4. What is the most effective strategy to educate people with asthma and health professionals about managing the adverse effects of drug therapies? 5. What is the most effective way of managing asthma triggers? 6. What is the role of complementary therapies in asthma management? 7. What are the benefits of breathing exercises as a form of physical therapy for asthma? 8. What type of patient (children and adults) and health professional education is most effective in gaining asthma control? 9. What is the most effective way to manage consultations and asthma control in adolescence and young people? 10. Psychological interventions for adults with asthma? Post JLA Priorities – Asthma – Jan 2010 Asthma UK (Partner)

Priorities 1a and 1 b
Asthma UK is interested in the concerns that people with asthma have about steroid treatments for asthma (corticosteroids) and the effect that these concerns have on how they take their medicine. We are also intrigued to understand the perspectives of healthcare professionals on both the concerns and use of steroid treatments for asthma, and how their perspectives compare to what people affected by asthma tell us. Therefore in a joint project with Professor Rob Horne (based at the Centre for Behavioral Medicine within the School of Pharmacy in London) and Education for Health, we developed some questionnaire surveys to enable us to understand more about this subject, and asked people affected by asthma and healthcare professionals for their perspectives on it. We have received over 3,000 completed questionnaires from people with asthma or carers of children with asthma. In addition, we received completed questionnaires from more than 200 healthcare professionals. We are currently in the process of analysing all of the data arising from these questionnaires. The questionnaires intended for people with asthma and parents or carers of children with asthma aimed to establish:  their experiences of side effects  the level of information they have received about side effects  their use or their child’s use of steroid treatments  their approach to dealing with concerns about side effects  how they respond to their concerns  future needs they may have to help overcome concerns about steroids. There were two separate questionnaires for:  People with asthma who are currently receiving a steroid treatment (by inhaler or tablet) for their asthma or have done within the last three years.  Parents or carers of children with asthma who are currently receiving a steroid treatment (by inhaler or tablet) for their child’s asthma or have done within the last three years The questionnaires intended for healthcare professionals aimed to establish how healthcare professionals perceived that people with asthma, and parents or carers of children with asthma, would respond to the questions asked of them in their own questionnaires, based on the interactions that they have with people affected by asthma in their work. For example this included their perception of the most commonly reported side effects and concerns from people affected by asthma, and the associated effects on how they then take their steroid medicines.
Next steps are to analyse results and clarify understanding these treatment concerns
and identifying an appropriate intervention (December 2009).



Post JLA Priorities – Asthma – Jan 2010 Priority 3
. A vital study to boost people’s expectations about the level of control over asthma they can achieve. (Oct 2009) Priority 10
Belfast-based researchers are collecting preliminary evidence on the benefits of prescribing anti-depressants for people with severe asthma, who are also depressed, (October 2009) Priority 7
Breathing exercises and self-management question submitted to the HTA.
Strategy Development
Asthma UK currently has two research strategies, one for basic research and another
for clinical research, each with their own priority areas. “In our new strategic plan
beginning October 08, we will be moving towards developing a single research
strategy and obviously the JLA priorities will feed into discussions”. (Quote from J
Versnel, Director of R & D)
Cochrane Airways Group (member of partnership)
Priorities 1a and 1 b
Cates CJ, Lasserson TJ. Regular fixed-dose treatment with formoterol and inhaled
corticosteroids versus regular treatment with salmeterol and inhaled corticosteroids
for chronic asthma: serious adverse events (Protocol). Cochrane Database of
Systematic Reviews 2009, Issue 2. Art. No.: CD007694. DOI:
10.1002/14651858.CD007694.

Cates CJ, Lasserson TJ, Jaeschke R. Regular treatment with formoterol and inhaled
steroids for chronic asthma: serious adverse events. Cochrane Database of
Systematic Reviews 2009, Issue 2. Art. No.: CD006924. DOI:
10.1002/14651858.CD006924.pub2.

Authors' conclusions
It is not possible, from the data in this review, to reassure people with asthma that
inhaled corticosteroids with regular formoterol carries no risk of increasing mortality in
comparison to inhaled corticosteroids alone as all four deaths occurred among 6,594
people using inhaled corticosteroids with formoterol. On the other hand, we have
found no conclusive evidence of harm and there was only one asthma related death
registered during over 3,000 patient year observation on formoterol. In adults, the
decrease in asthma-related serious adverse events on regular formoterol with
inhaled corticosteroids was not accompanied by a decrease in all cause serious
adverse events. In children the number of events was too small, and consequently
the results too imprecise, to determine whether the increase in all cause non-fatal
serious adverse events found in the previous meta-analysis on regular formoterol
alone is abolished by the additional use of inhaled corticosteroids. Clinical decisions
and information for patients regarding regular use of formoterol have to take into
account the balance between known symptomatic benefits of formoterol and the
degree of uncertainty and concern associated with its potential harmful effects.
Post JLA Priorities – Asthma – Jan 2010
Implications for research
Future research should clearly specify the number of patients with fatal and non-fatal
serious adverse events by treatment group and cause. Any new surveillance study to
investigate the impact of regular formoterol and inhaled corticosteroids on all-cause
mortality would need to be very large.
Cates CJ, Cates MJ, Lasserson TJ. Regular treatment with formoterol for chronic
asthma: serious adverse events. Cochrane Database of Systematic Reviews 2008,
Issue 4. Art. No.: CD006923. DOI: 10.1002/14651858.CD006923.pub2.

Authors' conclusions
In comparison with placebo, we have found an increased risk of serious adverse
events with regular formoterol, and this does not appear to be abolished in patients
taking inhaled corticosteroids. The effect on serious adverse events of regular
formoterol in children was greater than the effect in adults, but the difference
between age-groups was not significant.
Implications for research
Data on all-cause serious adverse events should be more fully reported in medical
journals, and not combined with all adverse events or limited to those events that are
thought by the investigator to be drug-related.
Regular treatment with formoterol versus regular treatment with salmeterol for
chronic asthma: serious adverse events (Protocol). Cochrane Database of
Systematic Reviews 2009, Issue 2. Art. No.: CD007695. DOI:
10.1002/14651858.CD007695.

Cates CJ, Lasserson TJ, Jaeschke R. Regular treatment with salmeterol and inhaled
steroids for chronic asthma: serious adverse events. Cochrane Database of
Systematic Reviews 2009, Issue 3. Art. No.: CD006922. DOI:
10.1002/14651858.CD006922.pub2.

Authors' conclusions
No significant differences have been found in fatal or non-fatal serious adverse
events in trials in which regular salmeterol has been randomly allocated with inhaled
corticosteroids, in comparison to inhaled corticosteroids at the same dose. Although
10,873 adults and 1,173 children have been included in trials, the number of patients
suffering adverse events is too small, and the results are too imprecise to confidently
rule out a relative increase in all-cause mortality or non-fatal adverse events. It is
therefore not possible to determine whether the increase in all-cause non-fatal
serious adverse events reported in the previous meta-analysis on regular salmeterol
alone is abolished by the additional use of regular inhaled corticosteroids. The
absolute difference between groups in the risk of serious adverse events was small.
There were no asthma-related deaths and few asthma-related serious adverse
events. Clinical decisions and information for patients regarding regular use of
salmeterol have to take into account the balance between known symptomatic
benefits of salmeterol and the degree of uncertainty and concern associated with its
potential harmful effects.
Implications for research
Studies on children are currently lacking in this area. In order to further quantify the
risks of regular salmeterol with inhaled corticosteroids a large-scale surveillance
study is required. Future research should clearly specify the number of patients with
Post JLA Priorities – Asthma – Jan 2010 fatal and non-fatal serious adverse events by treatment group and cause, and
outcomes should be verified by an independent outcome panel.
Cates CJ, Cates MJ. Regular treatment with salmeterol for chronic asthma: serious
adverse events. Cochrane Database of Systematic Reviews 2008, Issue 3. Art. No.:
CD006363. DOI: 10.1002/14651858.CD006363.pub2.

Authors' conclusions
In comparison with placebo, we have found an increased risk of serious adverse
events with regular salmeterol. There is also a clear increase in risk of asthma-
related mortality in patients not using inhaled corticosteroids in the two large
surveillance studies. Although the increase in asthma-related mortality was smaller in
patients taking inhaled corticosteroids at baseline, the confidence interval is wide, so
it cannot be concluded that the inhaled corticosteroids abolish the risks of regular
salmeterol. The adverse effects of regular salmeterol in children remain uncertain
due to the small number of children studied.

Implications for research
Data on serious adverse events should be more fully reported in medical journals. In
view of the increasing use of salmeterol in combination with inhaled corticosteroids,
further studies investigating the impact of salmeterol alone on serious adverse events
in adults may not be feasible, but studies using a combination of salmeterol and
inhaled steroids should collect and fully report data on fatal and non-fatal serious
adverse events. The evidence base for assessing the risks and benefits of salmeterol
in children is currently weak.
Priority 1a
Dissertation by Njeri Kigundu.

Short-acting beta 2-agonists (SABAs) are the mainstay of treatment for acute
symptoms of asthma. Research into the long term effects of SABAs has been
identified as a priority by patients. The dissertation assesses the incidence,
prevalence and risk of long-term adverse events associated with SABA use.
(Unpublished at present)
Post JLA Priorities – Asthma – Jan 2010

Source: http://www.jla.nihr.ac.uk/pdfs/Asthma/Post_JLA_priorities_Asthma_January_2010.pdf