Limits...
Real-world research and its importance in respiratory medicine.

Price D, Brusselle G, Roche N, Freeman D, Chisholm A - Breathe (Sheff) (2015)

Bottom Line: The result is that respiratory cRCTs often enrol a small, non-representative subset of patients and overlook the important interplay and interactions between patients and the real world, which can effect treatment outcomes.The Respiratory Effectiveness Group (REG), in collaboration with the European Academy of Allergy and Clinical Immunology (EAACI) and the European Respiratory Society (ERS), is developing quality appraisal tools and methods for integrating different sources of evidence.A REG/EAACI taskforce aims to help support future guideline developers to avoid a one-size-fits-all approach to recommendations and to tailor the conclusions of their meta-analyses to the populations under consideration.

View Article: PubMed Central - PubMed

Affiliation: Respiratory Effectiveness Group, Cambridge, UK ; University of Aberdeen, Aberdeen, UK.

ABSTRACT

Educational aims: To improve understanding of: The relative benefits and limitations of evidence derived from different study designs and the role that real-life asthma studies can play in addressing limitations in the classical randomised controlled trial (cRCT) evidence base.The importance of guideline recommendations being modified to fit the populations studied and the model of care provided in their reference studies.

Key points: Classical randomised controlled trials (cRCTs) show results from a narrow patient group with a constrained ecology of care.Patients with "real-life" co-morbidities and lifestyle factors receiving usual care often have different responses to medication which will not be captured by cRCTs if they are excluded by strict selection criteria.Meta-analyses, used to direct guidelines, contain an inherent meta-bias based on patient selection and artificial patient care.Guideline recommendations should clarify where they related to cRCT ideals (in terms of patient populations, medical resources and care received) and could be enhanced through inclusion of evidence from studies designed to better model the populations and care approaches present in routine care.

Summary: Clinical practice requires a complex interplay between experience and training, research, guidelines and judgement, and must not only draw on data from traditional or classical randomised controlled trials (cRCTs), but also from pragmatically designed studies that better reflect real-life clinical practice. To minimise extraneous variables and to optimise their internal validity, cRCTs exclude patients, clinical characteristics and variations in care that could potentially confound outcomes. The result is that respiratory cRCTs often enrol a small, non-representative subset of patients and overlook the important interplay and interactions between patients and the real world, which can effect treatment outcomes. Evidence from real-life studies (e.g. naturalistic or pragmatic clinical trials and observational studies encompassing healthcare database studies and cohort studies) can be combined with cRCT evidence to provide a fuller picture of intervention effectiveness and realistic treatment outcomes, and can provide useful insights into alternative management approaches in more challenging asthma patients. The Respiratory Effectiveness Group (REG), in collaboration with the European Academy of Allergy and Clinical Immunology (EAACI) and the European Respiratory Society (ERS), is developing quality appraisal tools and methods for integrating different sources of evidence. A REG/EAACI taskforce aims to help support future guideline developers to avoid a one-size-fits-all approach to recommendations and to tailor the conclusions of their meta-analyses to the populations under consideration.

No MeSH data available.


Related in: MedlinePlus

Mean (95% CI) difference between non-smokers and smokers with asthma, Suggesting alternatives to higher-dose ICS may be required. *: p≤0.01 for smokers versus non-smokers. Reproduced from [36] with permission from the publisher.
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Figure 5: Mean (95% CI) difference between non-smokers and smokers with asthma, Suggesting alternatives to higher-dose ICS may be required. *: p≤0.01 for smokers versus non-smokers. Reproduced from [36] with permission from the publisher.

Mentions: To explore the interaction of a current smoking status on ICS treatment, patients with mild asthma (n=95) were recruited to a multi-centre, double-blind, parallel-group study to compare the differential outcomes of inhaled beclomethasone dipropionate (BDP) at doses of 400 or 2000 µg in smokers and nonsmokers. Patients in both the smoking and nonsmoking arms were randomised to receive either 400 or 2000 µg BDP and the change in their morning peak expiratory flow (PEF) was measured over a 12-week outcome period. After 12 weeks of inhaled BDP therapy, there was a considerable difference in changes in morning PEF between smokers and nonsmokers. Interestingly, this difference was less pronounced in the 2000 µg BDP arm than in the 400 µg BDP arm (fig. 5). In other words, the magnitude of treatment effect on morning PEF was much greater in nonsmokers than in smokers at the 400 µg dosage, while it was similar at the high dosage. Similarly, while there was a significantly higher exacerbation rate among smokers compared with nonsmokers in the 400 µg BDP treatment arm (6 versus 1, respectively), no significant difference was seen in exacerbation rates in patients receiving the high 2000 µg BDP daily dose (1 versus 2, smokers versus non-smokers, respectively). These data not only build on the results of studies showing diminished ICS efficacy in mild smoking asthma patients treated on low-dose ICS, but also suggest the disparity between treatment response in smokers and non-smokers appears to be reduced at higher ICS doses and may support consideration of higher dose ICS use in asthma patients with a current smoking status [34, 36].Figure 5


Real-world research and its importance in respiratory medicine.

Price D, Brusselle G, Roche N, Freeman D, Chisholm A - Breathe (Sheff) (2015)

Mean (95% CI) difference between non-smokers and smokers with asthma, Suggesting alternatives to higher-dose ICS may be required. *: p≤0.01 for smokers versus non-smokers. Reproduced from [36] with permission from the publisher.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4487388&req=5

Figure 5: Mean (95% CI) difference between non-smokers and smokers with asthma, Suggesting alternatives to higher-dose ICS may be required. *: p≤0.01 for smokers versus non-smokers. Reproduced from [36] with permission from the publisher.
Mentions: To explore the interaction of a current smoking status on ICS treatment, patients with mild asthma (n=95) were recruited to a multi-centre, double-blind, parallel-group study to compare the differential outcomes of inhaled beclomethasone dipropionate (BDP) at doses of 400 or 2000 µg in smokers and nonsmokers. Patients in both the smoking and nonsmoking arms were randomised to receive either 400 or 2000 µg BDP and the change in their morning peak expiratory flow (PEF) was measured over a 12-week outcome period. After 12 weeks of inhaled BDP therapy, there was a considerable difference in changes in morning PEF between smokers and nonsmokers. Interestingly, this difference was less pronounced in the 2000 µg BDP arm than in the 400 µg BDP arm (fig. 5). In other words, the magnitude of treatment effect on morning PEF was much greater in nonsmokers than in smokers at the 400 µg dosage, while it was similar at the high dosage. Similarly, while there was a significantly higher exacerbation rate among smokers compared with nonsmokers in the 400 µg BDP treatment arm (6 versus 1, respectively), no significant difference was seen in exacerbation rates in patients receiving the high 2000 µg BDP daily dose (1 versus 2, smokers versus non-smokers, respectively). These data not only build on the results of studies showing diminished ICS efficacy in mild smoking asthma patients treated on low-dose ICS, but also suggest the disparity between treatment response in smokers and non-smokers appears to be reduced at higher ICS doses and may support consideration of higher dose ICS use in asthma patients with a current smoking status [34, 36].Figure 5

Bottom Line: The result is that respiratory cRCTs often enrol a small, non-representative subset of patients and overlook the important interplay and interactions between patients and the real world, which can effect treatment outcomes.The Respiratory Effectiveness Group (REG), in collaboration with the European Academy of Allergy and Clinical Immunology (EAACI) and the European Respiratory Society (ERS), is developing quality appraisal tools and methods for integrating different sources of evidence.A REG/EAACI taskforce aims to help support future guideline developers to avoid a one-size-fits-all approach to recommendations and to tailor the conclusions of their meta-analyses to the populations under consideration.

View Article: PubMed Central - PubMed

Affiliation: Respiratory Effectiveness Group, Cambridge, UK ; University of Aberdeen, Aberdeen, UK.

ABSTRACT

Educational aims: To improve understanding of: The relative benefits and limitations of evidence derived from different study designs and the role that real-life asthma studies can play in addressing limitations in the classical randomised controlled trial (cRCT) evidence base.The importance of guideline recommendations being modified to fit the populations studied and the model of care provided in their reference studies.

Key points: Classical randomised controlled trials (cRCTs) show results from a narrow patient group with a constrained ecology of care.Patients with "real-life" co-morbidities and lifestyle factors receiving usual care often have different responses to medication which will not be captured by cRCTs if they are excluded by strict selection criteria.Meta-analyses, used to direct guidelines, contain an inherent meta-bias based on patient selection and artificial patient care.Guideline recommendations should clarify where they related to cRCT ideals (in terms of patient populations, medical resources and care received) and could be enhanced through inclusion of evidence from studies designed to better model the populations and care approaches present in routine care.

Summary: Clinical practice requires a complex interplay between experience and training, research, guidelines and judgement, and must not only draw on data from traditional or classical randomised controlled trials (cRCTs), but also from pragmatically designed studies that better reflect real-life clinical practice. To minimise extraneous variables and to optimise their internal validity, cRCTs exclude patients, clinical characteristics and variations in care that could potentially confound outcomes. The result is that respiratory cRCTs often enrol a small, non-representative subset of patients and overlook the important interplay and interactions between patients and the real world, which can effect treatment outcomes. Evidence from real-life studies (e.g. naturalistic or pragmatic clinical trials and observational studies encompassing healthcare database studies and cohort studies) can be combined with cRCT evidence to provide a fuller picture of intervention effectiveness and realistic treatment outcomes, and can provide useful insights into alternative management approaches in more challenging asthma patients. The Respiratory Effectiveness Group (REG), in collaboration with the European Academy of Allergy and Clinical Immunology (EAACI) and the European Respiratory Society (ERS), is developing quality appraisal tools and methods for integrating different sources of evidence. A REG/EAACI taskforce aims to help support future guideline developers to avoid a one-size-fits-all approach to recommendations and to tailor the conclusions of their meta-analyses to the populations under consideration.

No MeSH data available.


Related in: MedlinePlus