The problem with critical and non-critical inhaler errors Federico Lavorini MD, PhD Dept. Experimental and Clinical Medicine Careggi University Hospital Florence, Italy
Presenter disclosures Federico Lavorini has no shares in any pharmaceutical companies, or in the tobacco industry. He has received sponsorship to carry out studies and lecture fees, and has had consultancy agreements from the following companies: AstraZeneca, Boehringer Ingelheim, CIPLA, Chiesi, GlaxoSmithKline, Mundipharma, Novartis, Orion, TEVA Pharmaceuticals, Trudell Medical International.
Outline 1. Inhaler use: Randomised Control Trials vs Real Life studies; 2. Definition(s), frequency and effects of inhaler errors on disease outcomes; 3. How to reduce detrimental effects of inhaler errors on disease outcomes.
Outline 1. Inhaler use: Randomised Control Trials vs Real Life studies 2. Definitions, frequency and effects of inhaler errors on disease outcomes 3. How to reduce detrimental effects of errors on disease outcomes
Randomised Controlled Trials Gold standard for providing information on efficacy of a treatment. They are designed to test a therapeutic hypothesis under optimal setting in the absence of confounding factors Strength: high internal validity Weakness: low external validity, i.e. poor generalisability Real Life studies Analysis of data collected under real-world conditions. They provide insights into the real life effectiveness of a medical condition or intervention Strength: high external validity, i.e. generalisability Weakness: low internal validity
Selection of asthma patients for a typical RCT 1000 900 800 100% ELIGIBLE TO RECRUIT: 1.3% Patients selected in RCTs Number of patients 700 600 500 400 300 38.4% 200 100 14.3% 5.7% 3.7% 2.1% 1.7% 0 VAS<2.5 FEV 1 50-85% No comorbidity Reversibility Pack < 10 years ICS Symptoms Herland K, et al. Respir Med 2005;99:11-9. Exclusion criteria Patients in everyday Clinical Practice
Patient adherence in RCTs vs RL studies Randomised controlled trials Real-life studies 100 80 75 125 75 125 89 >95 >80 100 80 Percentage of Patients 60 40 20 Percentage of Patients 60 40 20 45 34 17 49 14.1 8.3 34 21 40 0 1 2 3 4 5 0 1 2 3 4 5 6 7 8 9 RCT references 1) Pauwels R, et al. N Engl J Med 1997 2) Kips J, et al. Am J Respir Crit Care 2000 3) Bateman E. Am J Respir Crit Care 2004 4) Papi A, et al. Eur Respir J 2007 5) Busse W, et al. J Allergy Clin Immunol 2008 Real-life references 1) Partridge. Pulm Med 2006 2) De Marco, et al. Int Arch Allergy Immunol 2005 3 and 4) Janson, et al. Eur Respir J 2001 3=Italy 4=UK 5 and 6) Breekveldt-Postma, et al. Pharmaco-epidemiol Drug Saf 2008 5=fixed combination 6=ICS 7) Stallberg, et al. Resp Med 2003 8) Adams, et al. J Allergy Clin Immunol 2002 9) Corrigan. Prim Care Resp J 2011
Inhaler technique: RCTs vs real life studies RCTs Inclusion criteria: patients have perfect inhaler technique Inhaler technique checked and corrected regularly Inhaler diary kept to ensure compliance Expertly-trained clinical staff specialising in one subject Research staff often available to patient 24 hours a day Real life studies Patients will have a range of abilities with inhaler use Inhaler training 1 per year Patient may not be fully compliant with taking medication Health care professionals with variable level of clinical expertise Patient has usual care Courtesy by D. Price
Inhalers misuse is a major additional cause of non-adherence in real life
Outline 1. Inhaler use: Randomised Control Trials vs Real Life studies 2. Definition(s), Frequency and Effects of inhaler errors on disease outcomes 3. How to reduce detrimental effects of errors on disease outcomes
Definitions 2008 Preparation Errors Inhalation Errors Courtesy dr. J. Pritchard A critical error is one that may impact the effectiveness of the delivered drug, leading to sub-optimal disease control; A non-critical error is one of the checklist steps for a particular device that is not classified as critical
Definitions Aim: to define critical errors with pmdis and DPIsand their impact on health outcomes and resource use. The systematic review (2004-2016) consisted of two distinct searches: search-1: definitions and descriptions of critical errors; search-2: economic models on the cost of critical errors and patient burden.
Definitions search-1 results: - 299 descriptions of critical errors across the device types. -Even for the same inhaler device type, different terminology used between different authors to describe the same error; An action resulting in little or no medicine being inhaled or reaching the lungs A critical error would certainly affect inhalation and drug delivery A critical error could affect inhalation and drug delivery 14 13 27 A critical error would make aerosol therapy useless 14 A critical error would make aerosol therapy useless affecting inhalation or drug delivery 1
Effects of errors search-2 results: 5 studies with odds ratios linked inhaler errors with disease outcomes; 8 studies linked inhaler errors to economic burden. * *, from Roggeri et al Int J Chron Obstruct Pulmon Dis. 2016;11:597 602
Frequency 2016;150:394-406. Inhaler use by patients over the past 50 years
Frequency Aim: to provide an estimate of error rates (the proportion of patients with 1 critical or non-critical error) by device type and to evaluate the factors associated with inhaler misuse. Search results : 72 studies were extracted and included in the SR; 40 were selected for inclusion in the MA. The majority (54%) of the 72 identified studies comprised patients with both asthma and COPD, while 32% and 14% were conducted in either asthma or COPD, respectively.
Frequency Overall error frequency Critical error frequency pmdis pmdis DPIs DPIs Overall and critical error rates ranged from 50 to 100% and from 14 to 92% respectively; Between-study heterogeneity >90% indicating a large variability between studies.
Effects of errors 2017 Q: Which inhaler errors have the greatest impact on Asthma Outcomes? Inhaler-specific serious errors in asthma patients
Effects of errors Associations between DPI errors and uncontrolled asthma or exacerbations Adjusted OR (95 CI) Turbuhaler 1.30 (1.08-1.57)* Insufficient inspiratory flow No empty lungs before inhalation Error rate: 32% Diskus Error rate: 38% Turbuhaler Error rate: 26% Diskus 1.29 (1.04-1.60)* 1.56 (1.17-2.07)* 1.55 (1.16-2.06)* 1.06 (0.88-1.30) 1.07 (0.86-1.33) 1.34 (0.99-1.80) Insufficient inspiratory effort is significantly associated with: An increased likelihood of uncontrolled asthma An increased likelihood of exacerbation Error rate: 32% 0.94 (0.71-1.97) *P<0.01 0.3 0.5 0.8 1.0 1.3 2.0 5.0 asthma control improved fewer exacerbations asthma control reduced more exacerbations Adapted from Price D, et al. J Allergy Clin Immunol Pract 2017;5:1071-81.
Effects of errors Associations between pmdi errors and uncontrolled asthma or exacerbations Adjusted OR (95 CI) Lack of device knowledge, incorrect second dose preparation, timing or inhalation Error rate: 34% Incorrect head position Error rate: 34% 1.48 (1.10-2.00)* 0.94 (0.64-1.39) 1.31 (0.96-1.80)* 1.17 (0.78-1.75) The most frequent (47%) error, inspiratory effort not slow and deep, was not associated with uncontrolled asthma nor increased exacerbation rates No empty lungs before inhalation Hand-breath dis-coordination Error rate: 25% Error rate: 25% 1.41 (0.99-2.01)* 1.05 (0.71-1.54) 1.55 (1.11-2.16)* 1.38 (0.97-1.97) pmdi errors are associated with an increased likelihood of uncontrolled asthma but not with increased exacerbation rates 0.3 0.5 0.8 1.0 1.3 2.0 5.0 *P<0.01 asthma control improved fewer exacerbations asthma control reduced more exacerbations Adapted from Price D, et al. J Allergy Clin Immunol Pract 2017;5:1071-81.
Effects of errors 2017 100 100 100 100 80 80 80 80 60 60 60 60 40 40 40 40 20 20 20 20 0 0 0 0 No errors Critical errors Device independent errors Device dependent errors Critical errors were defined as those that could substantially affect dose delivery to the lungs. They were associated with an increased rate of exacerbations(or 1.86, CI 1.14-3.04)
Outline 1. Inhaler use: Randomised Control Trials vs Real Life studies 2. Definition(s), frequency and effects of inhaler errors on disease outcomes 3. How to reduce detrimental effects of errors on disease outcomes
How to reduce detrimental effects of errors on disease outcomes Identification of patients at risk and match the inhaler to the patient; Use of technologies; Education.
Ihaler error rate increases with patient s age and with the degree of airway obstruction
623 adult asthma patients using Diskus DPI (iharp database) withe columns: 0 error vs red columns: 1 error Serious inhaler errors are more common among female and obese patients. Other factors associated with serious errors are an asthma-related hospitalisation, lack of a prior inhaler technique review and poor asthma control. These findings can aid in identifying patients who could benefit from a review of their inhaler technique.
Suggested hierarchy for best match Conscious inhalation possible Sufficient inspiratory flow Patients with severe hyperinflation and during exacerbations Coordination + Coordination Poor hand-lung coordination pmdi±spacer DPI Breath-actuated aerosol Soft mist inhaler pmdi+ spacer DPI Breath-actuated aerosol Patient Insufficient inspiratory flow Coordination + Coordination pmdi±spacer Breath-actuated aerosol Soft mist inhaler pmdi+ spacer Breath-actuated aerosol Nebuliser Conscious inhalation not possible Elderly patients with cognitive limitations Poor hand-lung coordination pmdi+ spacer Nebuliser
How to reduce detrimental effects of errors on disease outcomes Identification of patients at risk and match the inhaler to the patient; Useoftechnologies; Education.
INCA Technology- Objective measurement of inhaler use Acoustic recording device attached to inhaler Device creates audio files of each step of inhaler use Patient uses inhaler Calendar Graph Clinician uses the information to educate the patient Mathematical analysis-to automatically identify when and howwell the inhaler was used
Good Poor inspiratory effort Exhale before inhale Drug dumping
* * * * * Deposition of the dry powder inhaler all around the mouthpiece with low inspiratory error. The INCA electronic monitor is able to identify that the most critical errors with the Diskus inhaler
How to reduce detrimental effects of errors on disease outcomes Identification of patients at risk and match the inhaler to the patient; Use of technologies; Education.
Management of chronic airway disease is 10% medication and 90% education Respir Care 2005; 50(10) 1360-74
* * *Lower scores = Better results One instruction is not enough!
Effect of inhaler training in asthma patients Adapted from Harnett CM et al. J Asthma 2014;51:440 5
69 moderate tosevere COPD using pmdi or DPIs. Inhaler technique assessed by checklists. A15-20 min nurse training/week/3 monthsbyusingverbalpresentation and video demonstration. A planned inhaler training program decreasesattacks, emergency visits and improvesqol in COPD patients.
Concluding remarks Inhaler errors are common and have detrimental effects on outcomes in asthma and COPD; There are wide discrepancies within the literature regarding definitions and descriptions of inhaler errors and their classification as either critical or non-critical; The different definitions of critical errors could contribute to extremely different conclusions even with the same inhaler type; thus, it is difficult to determine whether a particular inhaler type is inherently more vulnerable to critical errors. There is an urgent need for a consensus in the way in which critical and non-critical inhaler errors are defined. Future research can and should adopt more consistent inhaler technique checklists.
Thankyouverymuchfor yourkindattention!! Questions? http://www.admit-inhalers.org