Systematic Review of Cost-Effectiveness and Healthcare Resource Utilization in Chronic Cough

Studies were assessed for inclusion based on the PICOTS criteria outlined in Table 1. The target population was adult patients diagnosed with RCC or UCC, according to American College of Chest Physicians (ACCP) guidelines [16 (link)]. Due to the heterogeneity in defining CC across studies, the population search strings were expanded to include all patients with CC as defined by the study investigators. Cost-effectiveness and HCRU studies were assessed against the same eligibility criteria, with the exception of the intervention and comparators. Cost-effectiveness studies were considered for inclusion if any medication known to be used for the treatment of CC, including off-label medications, compared to placebo, best supportive care, or any other intervention of interest, were reported. HCRU studies were not restricted by intervention or comparator to account for studies reporting costs and/or resource use independent of treatment effects. Outcomes of interest included costs combined with measures of effectiveness, and HCRU outcomes such as total healthcare costs, direct costs, indirect costs, out-of-pocket costs, and resource utilization. Relevant studies were limited to English language publications only, and no time or geographical restrictions were imposed.
Table 1

Eligibility criteria for SLR study inclusion

Criteria	Inclusion	Exclusion
Population	> 18 + years old > Have clinical evidence of CC (as defined by the study investigators) > Subgroups of interest: CC duration ≥ 1 year and < 1 year	> Patients with history of malignancy, respiratory tract infection, chronic bronchitis, or substance abuse > Currently taking an angiotensin-converting enzyme inhibitor > Immunocompromised patients > Patients with cough resulting from invasive respiratory tract instrumentation (e.g., ventilator dependent, tracheostomy, endotracheal intubation)
Interventions	Cost-effectiveness: > Gefapixant > Antitussive medications (e.g., opiates (codeine, hydrocodone), noscapine (narcotine), dextromethorphan, respiratory anesthetics (benzonatate)) > Protussive medications (e.g., expectorants (guaifenesin), mucolytic or mucus modifying agents (acetylcysteine, dornase alfa inhaled)) > Non-antitussive/non-protussive medications (e.g., antihistamines, antibiotics (azithromycin), anticholinergics, bronchodilators) > Neuromodulators/antidepressants (e.g., amitriptyline, gabapentin, baclofen, pregabalin, nortriptyline) > Inhaled corticosteroids (e.g., beclomethasone, budesonide, fluticasone, mometasone) > Note: These treatments were eligible if given with or without a combined non-pharmacological treatment (e.g., chest physical therapy, cognitive behavioral therapy, speech therapy, behavioral cough suppression therapy, acupuncture, tai chi, yoga, meditation, aroma therapy, humidifiers, herbal tea). Additionally, studies were eligible for inclusion if patients with RCC received concomitant treatment for the underlying cause (e.g., inhaled beta2-agonists for asthma, proton pump inhibitors for gastroesophageal reflux disease) HCRU: > Not restricted
Comparisons	Cost-effectiveness: > Placebo or best supportive care > Any intervention of interest HCRU: > No restricted
Outcomes	Cost-effectiveness: > Costs combined with clinical endpoints (e.g., clinical outcomes, utilities, QALYs, resource use, burden of illness) expressed in incremental costs, incremental cost-effectiveness ratios, QALYs, or any other measure of effectiveness reported together with costs HCRU: > Total healthcare costs (both direct and indirect costs) > Direct costs (e.g., costs for drugs, inpatient, outpatient, emergency room, procedures, physician visits, diagnostic/screening services, rehabilitation in a facility or at home, community-based services, medical devices, aids and appliances, alternative care) > Indirect costs (e.g., societal costs, patient productivity loss, caregiver absenteeism i.e., cost of caregiver taking time off paid work to provide care) > Out-of-pocket costs (e.g., copayments for drugs, specialty assistive devices, special transportation) > Resource utilization
Time	> Not restricted
Study design	Cost-effectiveness: > Full economic evaluations - Cost-effectiveness analyses - Cost utility analyses - Cost-benefit analyses - Cost consequence studies - Cost minimisation analyses > HTAs > Pooled analyses presenting cost or resource use estimates > Literature reviews summarizing results of primary research studies and/or economic evaluations HCRU: > Full economic evaluations - Cost-effectiveness analyses - Cost utility analyses - Cost-benefit analyses - Cost consequence studies - Cost minimization analyses > Partial economic evaluations - Budget impact models - Non-comparative economic studies (e.g., cost of illness studies) > Observational studies - Prospective and retrospective cohort studies - Case-control studies - Cross-sectional studies - Controlled and uncontrolled longitudinal studies - Controlled before-and-after studies - Interrupted time series studies - Historically controlled studies - Time and motion studies > Randomized controlled trials > Non-randomized clinical trials > Controlled before-and-after trials > HTAs > Pooled analyses presenting cost or resource use estimates > Literature reviews summarizing results of primary research studies and/or economic evaluations^a
Other	> English language only
Region	> Global

^aLiterature reviews involving a systematic approach to study identification and selection were of interest for the purposes of cross-referencing (e.g., SLRs, structured literature reviews, scoping reviews, landscape reviews). Narrative reviews that did not involve systematic study identification and selection or that primarily summarized an author’s viewpoints were not of interest

CC: chronic cough; HCRU: healthcare resource utilization; HTA: health technology assessment; QALY: quality-adjusted life year; RCC: refractory chronic cough; SLR: systematic literature review

Screening of all titles and abstracts identified in the search was conducted by two independent reviewers. Citations considered eligible for inclusion by both reviewers were advanced to full-text screening, which involved independent assessment of the full-text articles for inclusion by the same two reviewers. A third reviewer provided arbitration in the case of discrepancy. Each study was counted once through mapping of citations to corresponding studies.

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Bali V., Adriano A., Byrne A., Akers K.G., Frederickson A, & Schelfhout J. (2023). Understanding the economic burden of chronic cough: a systematic literature review. BMC Pulmonary Medicine, 23, 416.

Publication 2023

Acetylcysteine Acupuncture Adult Agonists Aids Amitriptyline Anesthetics Angiotensin converting enzyme inhibitor Antibiotics Anticholinergics Antidepressants Antihistamines Antitussive medications Aroma therapy Assistive devices Asthma Azithromycin Baclofen Beclomethasone Behavioral therapy Benzonatate Bronchodilators Budesonide Chest Chronic bronchitis Codeine Cognitive behavioral therapy Corticosteroids Cough Dextromethorphan Dornase alfa Drugs Eligibility Endotracheal intubation Expectorants Fluticasone Gabapentin Gastroesophageal reflux disease Gefapixant Guaifenesin Health technology assessment Herbal tea Heterogeneity Home services Hydrocodone Inpatient Malignancy Medical devices Medications label Meditation Mometasone Mucolytic Mucus Narcotine Neuromodulators Nortriptyline Opiates Outpatient Patient Pharmacological treatment Physical therapy Physician Picots Placebo Pregabalin Proton pump inhibitors Respiratory Respiratory tract Respiratory tract infection Speech therapy Substance abuse Target population Tracheostomy Yoga

Corresponding Organization :

Other organizations : MSD (United States), Health Economics and Outcomes Research (United Kingdom)

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Variable analysis

independent variables

Interventions: Gefapixant, antitussive medications, protussive medications, non-antitussive/non-protussive medications, neuromodulators/antidepressants, inhaled corticosteroids, any combined non-pharmacological treatment, and concomitant treatment for underlying cause in patients with RCC

dependent variables

Cost-effectiveness: Costs combined with clinical endpoints (e.g., clinical outcomes, utilities, QALYs, resource use, burden of illness) expressed in incremental costs, incremental cost-effectiveness ratios, QALYs, or any other measure of effectiveness reported together with costs
HCRU: Total healthcare costs, direct costs, indirect costs, out-of-pocket costs, and resource utilization

control variables

Comparisons: Placebo, best supportive care, or any intervention of interest for cost-effectiveness studies; no restrictions for HCRU studies

positive controls

Not explicitly mentioned

negative controls

Not explicitly mentioned

Annotations

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