Figures
- FIGURE 1
INTREPID study design. Only two study visits (baseline and week 24) will be required during the INTREPID study. FEV1 and critical error assessments will be conducted in select patient subgroups only. CAT: COPD assessment test; COPD: chronic obstructive pulmonary disease; FEV1: forced expiratory volume in 1 s; ICS: inhaled corticosteroid; LABA: long-acting β2-agonist; LAMA: long-acting muscarinic antagonist; R: randomisation. #: ICS/LAMA/LABA multiple-inhaler triple therapy, LAMA/LABA combination dual therapy or ICS/LABA combination dual therapy.
- FIGURE 2
Recruitment models employed across countries. CRO: contract research organisation; DE: Germany; NL: the Netherlands; PI: principal investigator; PIC: patient identification centre; SP: Spain; SWE: Sweden; UK: United Kingdom.
Tables
- TABLE 1
A comparison of the key features that differ between conventional randomised controlled trials (RCTs) and effectiveness trials
Conventional RCTs Randomised effectiveness trials Trial setting Often academic/research centres specially equipped for clinical research, which patients may have to travel considerable distance to attend [5].
Trial patients often attend frequent, regular study visits with a specialist investigator [5].
Patients are provided with regular training during study visits to ensure optimal medication use and adherence [6]. Adherence to study medication is monitored.Routine care practices and hospitals.
Patients treated by their (local) regular healthcare provider in accordance with usual clinical care; limited or no study-specific visits required.
Training and medication guidance is given as part of usual clinical care. This varies between sites and countries.
Patients may change their treatment at physician or patient discretion.Patient selection Narrow population due to strict inclusion and exclusion criteria [7, 8]; recruitment of patients with comorbid conditions and concomitant medications is limited [5, 7–9]. Enrolment of a broader patient population creates high external validity as patients are more representative of the population seen in usual practice [8, 10]. Key differences between protocol-defined study treatments and those given in clinical practice Often employ a placebo group or strictly controlled comparator group to enable direct comparison of pure drug effects providing high internal validity [10]. Comparator treatments are aligned with physician and country usual standard of care. Measurement of outcomes Outcomes often those required by regulatory authority, which may not be used in the routine care of patients, such as physiological end-points or biomarkers [11]. Selected end-points are relevant to usual practice and include a more patient-centred focus [8]. Safety monitoring Exclusion of “high-risk” patients most likely to experience safety issues [5, 9].
Safety is closely monitored by investigators at each study visit.Enrolment of a wider population of patients allows collection of more generalisable safety data [10].
Patient safety is ensured through treating physicians during routine study visits or planned telephone calls. - TABLE 2
Key inclusion and exclusion criteria of the INTREPID study
Inclusion criteria Informed consent: capable of giving signed, informed consent Age and sex: male and female aged ≥40 years COPD diagnosis: documented physician diagnosis of COPD Severity of COPD symptoms: a score of ≥10 on CAT at screening History of exacerbations: a history of treatment with systemic/oral corticosteroids, antibiotics and/or hospitalisation for ≥1 COPD exacerbation in the 3 years prior to randomisation# Existing COPD maintenance treatment: currently receiving one of the below non-ELLIPTA maintenance therapies and have been prescribed it continually for ≥16 weeks prior to randomisation: ICS in combination with LAMA and LABA (MITT) LAMA and LABA combination therapy¶ ICS and LABA combination therapy¶ Exclusion criteria Unstable COPD: resolution of an exacerbation within 2 weeks of visit 1+ Prior/concomitant therapy with oral corticosteroid: chronic use of oral corticosteroid for respiratory or other indications in the opinion of the investigator§ Women of child-bearing potential: women who are pregnant, lactating or planning to become pregnant during the study period Medical conditions: any illness judged in the opinion of the investigator to cause a low probability of 6-month survival Other diseases/abnormalities: historical or current evidence of uncontrolled or clinically significant diseaseƒ Hypersensitivity: history of hypersensitivity to any corticosteroid, anticholinergic/muscarinic receptor antagonist, β2-agonist, lactose/milk protein or magnesium stearate, or a medical condition such as narrow-angle glaucoma, prostatic hypertrophy or bladder neck obstruction that, in the opinion of the investigator, contraindicates study participation Participation in interventional clinical studies: taking part in any investigational drug treatment within 30 days or five half-lives of the prior investigational drug before visit 1 CAT: COPD assessment test; LAMA: long-acting muscarinic antagonist; LABA: long-acting β2-agonist; MITT: multiple-inhaler triple therapy; ICS: inhaled corticosteroid. #: captured through patient recall and/or medical records and must be documented in patient notes. Prior use of systemic/oral corticosteroids and/or antibiotics alone does not qualify as exacerbation history unless treatment was associated with the worsening of COPD symptoms. ¶: patients on dual maintenance therapy on enrolment must be considered by their physician to require a step-up to triple therapy and the reason for the physician decision must be documented. +: patients may be rescreened 2 weeks after resolution of an exacerbation. §: chronic use is defined as more than 14 days' continuous use during the 12 weeks prior to visit 1; ƒ: significant disease is defined as any disease that, in the opinion of the investigator, would put the safety of the patient at risk by participating, or would impact the effectiveness or safety analysis if the disease/condition exacerbated during the study.
Jump To
- Article
- Abstract
- Abstract
- The importance of randomised controlled trials and factors limiting their applicability to usual clinical practice
- An introduction to effectiveness studies
- Rationale for the INTREPID study
- INTREPID: protocol of a randomised effectiveness study in usual practice
- Conclusion
- Acknowledgements
- Footnotes
- References
- Figures & Data
- Info & Metrics