The Joint Task Force on Practice Parameters GRADE guidelines for the medical management of chronic rhinosinusitis with nasal polyposis

These evidence-based guidelines support patients, clinicians, and other stakeholders in decisions about the use of intranasal corticosteroids (INCS), biologics, and aspirin therapy after desensitization (ATAD) for the management of chronic rhinosinusitis with nasal polyposis (CRSwNP). It is important to note that the current evidence on surgery for CRSwNP was not assessed for this guideline nor were management options other than INCS, biologics, and ATAD. The Allergy-Immunology Joint Task Force on Practice Parameters formed a multidisciplinary guideline panel balanced to include the views of multiple stakeholders and to minimize potential biases. Systematic reviews for each management option informed the guideline. The guideline panel used the Grading of Recommendations Assessment, Development and Evaluation approach to inform and develop recommendations. The guideline panel reached consensus on the following statements: (1) In people with CRSwNP, the guideline panel suggests INCS rather than no INCS (conditional recommendation, low certainty of evidence). (2) In people with CRSwNP, the guideline panel suggests biologics rather than no biologics (conditional recommendation, moderate certainty of evidence). (3) In people with aspirin (nonsteroidal anti-inflammatory drug)-exacerbated respiratory disease, the guideline panel suggests ATAD rather than no ATAD (conditional recommendation, moderate certainty of evidence). The conditions for each recommendation are discussed in the guideline. These evidence-based guidelines support patients, clinicians, and other stakeholders in decisions about the use of intranasal corticosteroids (INCS), biologics, and aspirin therapy after desensitization (ATAD) for the management of chronic rhinosinusitis with nasal polyposis (CRSwNP). It is important to note that the current evidence on surgery for CRSwNP was not assessed for this guideline nor were management options other than INCS, biologics, and ATAD. The Allergy-Immunology Joint Task Force on Practice Parameters formed a multidisciplinary guideline panel balanced to include the views of multiple stakeholders and to minimize potential biases. Systematic reviews for each management option informed the guideline. The guideline panel used the Grading of Recommendations Assessment, Development and Evaluation approach to inform and develop recommendations. The guideline panel reached consensus on the following statements: (1) In people with CRSwNP, the guideline panel suggests INCS rather than no INCS (conditional recommendation, low certainty of evidence). (2) In people with CRSwNP, the guideline panel suggests biologics rather than no biologics (conditional recommendation, moderate certainty of evidence). (3) In people with aspirin (nonsteroidal anti-inflammatory drug)-exacerbated respiratory disease, the guideline panel suggests ATAD rather than no ATAD (conditional recommendation, moderate certainty of evidence). The conditions for each recommendation are discussed in the guideline. Chronic rhinosinusitis with nasal polyposis (CRSwNP) is an inflammatory disease of the nasal mucosa and sinuses that lasts at least 12 weeks.1Stevens W.W. Schleimer R.P. Kern R.C. Chronic rhinosinusitis with nasal polyps.J Allergy Clin Immunol Pract. 2016; 4: 565-572Abstract Full Text Full Text PDF PubMed Scopus (269) Google Scholar It affects about 2% to 4% of people with symptoms such as smell loss, nasal obstruction, thick nasal drainage, and facial pressure.2Sedaghat A.R. Kuan E.C. Scadding G.K. Epidemiology of chronic rhinosinusitis: prevalence and risk factors.J Allergy Clin Immunol Pract. 2022; 10: 1395-1403Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar Some patients with CRSwNP also have comorbid asthma and develop acute respiratory reactions to nonsteroidal anti-inflammatory drugs. Patients with this clinical triad of conditions are classified as having aspirin (or nonsteroidal anti-inflammatory drug)-exacerbated respiratory disease (AERD). CRSwNP is important because it negatively impacts quality of life. While there is no known cure for CRSwNP, there are many different management options. Although optimal patient outcomes require systematic summaries of all available evidence,3Chu D.K. Golden D.B.K. Guyatt G.H. Translating evidence to optimize patient care using GRADE.J Allergy Clin Immunol. 2021; 9: 4221-4230Scopus (27) Google Scholar guidelines for the management of CRSwNP have historically not explicitly considered such summaries. Furthermore, several trials of interventions for CRSwNP were recently completed, calling for the need for updated clinical guidelines.4Peters A.T. Spector S. Hsu J. Hamilos D.L. Baroody F.M. Chandra R.K. et al.Diagnosis and management of rhinosinusitis: a practice parameter update.Ann Allergy Asthma Immunol. 2014; 113: 347-385Abstract Full Text Full Text PDF PubMed Scopus (145) Google Scholar, 5Slavin R.G. Spector S.L. Bernstein I.L. Kaliner M.A. Kennedy D.W. Virant F.S. et al.The diagnosis and management of sinusitis: a practice parameter update.J Allergy Clin Immunol. 2005; 116: S13-S47Abstract Full Text Full Text PDF PubMed Scopus (306) Google Scholar, 6Spector S.L. Bernstein I.L. Li J.T. Berger W.E. Kaliner M.A. Schuller D.E. et al.Parameters for the diagnosis and management of sinusitis.J Allergy Clin Immunol. 1998; 102: S107-S144Abstract Full Text Full Text PDF PubMed Google Scholar These guidelines are based on updated and original systematic reviews of evidence conducted and reported separately.7Chu D.K. Lee D.S. Lee K.M. Schünemann H.J. Szczeklik W. Lee J.M. Benefits and harms of aspirin desensitization for aspirin exacerbated respiratory disease: a systematic review and meta-analysis.Int Forum Allergy Rhin. 2019; 9: 1409-1419Crossref PubMed Scopus (35) Google Scholar, 8Bognanni A. Chu D.K. Rank M.A. Bernstein J. Ellis A.K. Golden D. et al.Topical corticosteroid for chronic rhinosinusitis with nasal polyposis: GRADE systematic review and network meta-analysis.J Allergy Clin Immunol. 2022 Aug 12; (S0091-6749(22)01050-8, online ahead of print)Abstract Full Text Full Text PDF Scopus (6) Google Scholar, 9Oykhman P. Paramo F.A. Bousquet J. Kennedy D.W. Brignardello-Petersen R. Chu D.K. Comparative efficacy and safety of monoclonal antibodies and aspirin desensitization for chronic rhinosinusitis with nasal polyposis: a systematic review and network meta-analysis.J Allergy Clin Immunol. 2022; 149: 1286-1295Abstract Full Text Full Text PDF PubMed Scopus (76) Google Scholar The panel followed best practices for guideline development recommended by the Institute of Medicine and the Guidelines International Network (GIN) and used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess the certainty in the evidence and formulate recommendations.10Alonso-Coello P. Oxman A.D. Moberg J. Brignardello-Petersen R. Akl E.A. Davoli M. et al.GRADE working group. GRADE evidence to decision (EtD) frameworks: a systematic and transparent approach to making well informed healthcare choices. 2: Clinical practice guidelines.BMJ. 2016; 353: i2089Crossref PubMed Scopus (609) Google Scholar The recommendations, along with key remarks and conditions to consider when choosing treatments, are listed in Table I.Table ISummary of the recommendationsQuestion 1: Should INCS (topical corticosteroid), rather than no INCS, be used in CRSwNP?Recommendation 1: In people with CRSwNP, the guideline panel suggests INCS rather than no INCS (conditional recommendation based on low certainty of evidence).RemarksFactors driving recommendation type:•The small-to-moderate treatment effect and low certainty evidence when all of the different INCS delivery methods were considered together for the 2 critical outcomes, disease-specific quality of life and nasal obstruction symptoms, balanced by the low burdens of medications, drove the conditional recommendation.Conditions that may be important during shared decision making:•The NMA linked to this guideline showed that delivery method of INCS was potentially important. INCS stent, spray, and EDS are among the most beneficial of the INCS delivery methods across multiple patient-important outcomes.•The costs, availability, accessibility, and practical implications of the different methods of INCS delivery are likely to influence patient decision making (see description of the interventions section).•There is moderate certainty of evidence for the safety of INCS spray but safety may vary among the other delivery options. There is low or very low certainty in the safety of INCS using delivery methods other than spray.•INCS have small treatment effect sizes. Patients with severe or rapidly recurrent disease may value more treatments with larger reductions in symptoms.•There is probably uncertainty in the value and importance patients put on the outcomes that patients consider critical to decision making.Question 2: Should biologics, rather than no biologics, be used CRSwNP?Recommendation 2: In people with CRSwNP, the guideline panel suggests biologics rather than no biologics (conditional recommendation based on moderate certainty of evidence).RemarksFactors driving recommendation type:•The varying values and preferences among different populations of individuals with CRSwNP drove the conditional recommendation.Conditions that may be important during shared decision making:•For patients who have a symptom for which the improvement was considered to be important while receiving treatments other than biologics (ie, INCS, surgery, or ATAD), not using biologics may be preferred.•For patients using INCS for at least 4 weeks and who continue to have high disease burden, biologics may be preferred over other medical treatment choices.•For patients who have higher disease severity at presentation, biologics may be preferred over other medical treatment choices.•There is variability in efficacy among the biologics and this may influence the overall choice. Dupilumab and omalizumab are the most beneficial for most patient-important outcomes when comparing with other biologics based on results from the Oykhman et al9Oykhman P. Paramo F.A. Bousquet J. Kennedy D.W. Brignardello-Petersen R. Chu D.K. Comparative efficacy and safety of monoclonal antibodies and aspirin desensitization for chronic rhinosinusitis with nasal polyposis: a systematic review and network meta-analysis.J Allergy Clin Immunol. 2022; 149: 1286-1295Abstract Full Text Full Text PDF PubMed Scopus (76) Google Scholar NMA linked to this guideline.•Patients who value not having the burden of payment and insurance approvals may be less likely to choose biologics.•Patients who want to avoid the inconvenience of trying potentially less effective medical therapies may prefer biologics.•In AERD specifically, biologics may be preferred over ATAD for patients who have increased risk of harms associated with daily aspirin therapy, in patients who value the most efficacious therapies, and/or in patients who wish to avoid a strict daily oral medication regimen and its associated initial desensitization procedure.•Patients with comorbid diseases that led to a dual indication for biologic treatment (eg, asthma) may be a reason to choose biologics in general and even specific biologics.Question 3: Should ATAD, rather than no ATAD, be used in people with AERD?Recommendation 3: In people with AERD, the guideline panel suggests ATAD rather than no ATAD (conditional recommendation based on moderate certainty of evidence).RemarksFactors driving recommendation type:•The benefit of ATAD is moderate and is balanced by the risk of adverse effects that can lead to discontinuation.Conditions that may be important during shared decision making:•Risks that impact the safety of performing an aspirin desensitization such as severe poorly controlled asthma.•Risks that impact safety of long-term aspirin use such as conditions or treatments that increase bleeding risk, such as age, male, low weight or BMI, hypertension, diabetes, smoking, prednisone use, or previous GI or intracranial bleed.•Biologics may be preferred over ATAD in AERD for patients who have increased risk of harms with ATAD or in patients who value the most efficacious therapies and/or who are avoiding a strict daily oral medication regimen and its associated desensitization procedure.•Patients intolerant to NSAIDs and who require an NSAID for alternative indications (eg. cardiovascular disease) may prefer ATAD over other options.BMI, Body mass index; NSAIDs, nonsteroidal anti-inflammatory drugs. Open table in a new tab BMI, Body mass index; NSAIDs, nonsteroidal anti-inflammatory drugs. The strength of a recommendation is expressed as either strong ("the guideline panel recommends"), or conditional ("the guideline panel suggests") and has the following interpretations. •For patients: Most fully informed people in this situation would want to follow the recommended course of action and only a small proportion would not.•For clinicians: Most individuals should receive the intervention or test. Formal decision aids are not likely to be needed to help individual patients make decisions consistent with their values and preferences.•For policy makers: The recommendation can be adopted as policy in most situations. Adherence to this recommendation according to the guideline could be used as a quality criterion or performance indicator. •For patients: The majority of fully informed people in this situation would want the suggested course of action, but many would not, and a discussion between them and their health care professional may help reach a decision (ie, shared decision making).•For clinicians: Recognize that different choices will be appropriate for individual patients and that you must help each patient arrive at a management decision consistent with their values and preferences. Decision aids may be useful in helping individuals to make decisions consistent with their values and preferences. For each conditional recommendation we provide key conditions to guide working with patients in choosing their best treatment course.•For policy makers: Policymaking will require substantial debate and involvement of various stakeholders. Performance measures about the suggested course of action should focus on documentation of appropriate decision-making processes. Informed by a published survey of patients and clinicians, the guideline panel rated disease-specific quality of life and nasal symptoms as critical for decision making. Avoiding adverse effects from interventions is also considered important. The guideline panel, however, noted that there was possibly important uncertainty and variability in how much people value the critical outcomes. Each recommendation is followed by remarks that further elaborate and contextualize the recommendation and important considerations to shape optimal shared decision making. The perspective of the guideline is that of the individual patient. These recommendations take into consideration cost, impact on health equity, acceptability by stakeholders, and feasibility of implementation. The Joint Task Force on Practice Parameters (JTF-PP) will create tools to facilitate the dissemination and implementation of the recommendations including oral presentations and an educational slide set. The consideration of aspirin therapy after desensitization (ATAD) is only applicable for people who have AERD, whereas intranasal corticosteroids (INCS) and biologics apply more broadly to all persons with CRSwNP. The purpose of this document is to evaluate the current evidence and provide guidance on the use of INCS and biologics for CRSwNP and ATAD for AERD. It is important to note that the current evidence on surgery for CRSwNP was not assessed for this guideline nor were management options other than INCS, biologics, and ATAD. The primary target audience of these guidelines are specialists in allergy-immunology, otorhinolaryngologists, pulmonologists, general practitioners, and allied health practitioners. This document may also serve as the basis for development and implementation of locally adapted guidelines. By identifying gaps in the research literature, these guidelines may help researchers direct attention to topics for which more studies are needed. CRSwNP is an inflammatory disease of the sinonasal mucosa of at least 12 weeks’ duration.1Stevens W.W. Schleimer R.P. Kern R.C. Chronic rhinosinusitis with nasal polyps.J Allergy Clin Immunol Pract. 2016; 4: 565-572Abstract Full Text Full Text PDF PubMed Scopus (269) Google Scholar CRSwNP affects about 2% to 4% of adults.2Sedaghat A.R. Kuan E.C. Scadding G.K. Epidemiology of chronic rhinosinusitis: prevalence and risk factors.J Allergy Clin Immunol Pract. 2022; 10: 1395-1403Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar The cardinal symptoms of CRSwNP are smell loss, nasal obstruction, thick nasal drainage, and facial pressure. Sinonasal symptoms adversely affect quality of life, including productivity, sleep, and exercise. People with CRSwNP often have comorbid asthma, an inflammatory condition of the lungs that causes reversible airflow obstruction and symptoms of shortness of breath, coughing, wheezing, and chest tightness. Severe asthma exacerbations cause emergency department visits, hospitalizations, and, rarely, death. Some mechanisms of inflammation, and therefore treatments, are common and shared between CRSwNP (upper airway inflammation) and asthma (lower airway inflammation). There is no known cure for CRSwNP. There are, however, many different management options for CRSwNP. Previous clinical guidelines have narratively reviewed management options such as surgery (endoscopic sinus surgery), systemic corticosteroids, saline rinses, INCS, antibiotics, aspirin therapy following desensitization, and biologics.4Peters A.T. Spector S. Hsu J. Hamilos D.L. Baroody F.M. Chandra R.K. et al.Diagnosis and management of rhinosinusitis: a practice parameter update.Ann Allergy Asthma Immunol. 2014; 113: 347-385Abstract Full Text Full Text PDF PubMed Scopus (145) Google Scholar, 5Slavin R.G. Spector S.L. Bernstein I.L. Kaliner M.A. Kennedy D.W. Virant F.S. et al.The diagnosis and management of sinusitis: a practice parameter update.J Allergy Clin Immunol. 2005; 116: S13-S47Abstract Full Text Full Text PDF PubMed Scopus (306) Google Scholar, 6Spector S.L. Bernstein I.L. Li J.T. Berger W.E. Kaliner M.A. Schuller D.E. et al.Parameters for the diagnosis and management of sinusitis.J Allergy Clin Immunol. 1998; 102: S107-S144Abstract Full Text Full Text PDF PubMed Google Scholar,11Orlandi R.R. Kingdom T.T. Smith T.L. Bleier B. DeConde A. Luong A.U. et al.International consensus statement on allergy and rhinology: rhinosinusitis 2021.Int Forum Allergy Rhinol. 2021; 11: 213-739Crossref PubMed Scopus (340) Google Scholar,12Fokkens W.J. Lund V.J. Hopkins C. Hellings P.W. Kern R. Reitsma S. et al.Executive summary of EPOS 2020 including integrative care pathways.Rhinology. 2020; 58: 82-111Crossref PubMed Scopus (0) Google Scholar The American Academy of Allergy, Asthma & Immunology (AAAAI)/American College of Allergy, Asthma, and Immunology (ACAAI) JTF-PP and CRSwNP work group members determined, through discussion, that the guideline would provide evidence-based guidance on 3 of these interventions: INCS, biologics, and ATAD. Several randomized controlled trials (RCTs) of these interventions for CRSwNP were recently completed, calling for the need for updated clinical guidelines specific to these interventions.7Chu D.K. Lee D.S. Lee K.M. Schünemann H.J. Szczeklik W. Lee J.M. Benefits and harms of aspirin desensitization for aspirin exacerbated respiratory disease: a systematic review and meta-analysis.Int Forum Allergy Rhin. 2019; 9: 1409-1419Crossref PubMed Scopus (35) Google Scholar, 8Bognanni A. Chu D.K. Rank M.A. Bernstein J. Ellis A.K. Golden D. et al.Topical corticosteroid for chronic rhinosinusitis with nasal polyposis: GRADE systematic review and network meta-analysis.J Allergy Clin Immunol. 2022 Aug 12; (S0091-6749(22)01050-8, online ahead of print)Abstract Full Text Full Text PDF Scopus (6) Google Scholar, 9Oykhman P. Paramo F.A. Bousquet J. Kennedy D.W. Brignardello-Petersen R. Chu D.K. Comparative efficacy and safety of monoclonal antibodies and aspirin desensitization for chronic rhinosinusitis with nasal polyposis: a systematic review and network meta-analysis.J Allergy Clin Immunol. 2022; 149: 1286-1295Abstract Full Text Full Text PDF PubMed Scopus (76) Google Scholar The target population for these recommendations is people with CRSwNP aged 18 years and older. Chronic rhinosinusitis without nasal polyposis is also an inflammatory disease of the nose and sinuses that lasts at least 12 weeks but differs from CRSwNP in that nasal polyps are not formed. CRSwNP is less common in people younger than 18 years old; however, recommendations for INCS and biologics may be appropriate for younger persons with CRSwNP or for conditions not considered in this guideline. CRSwNP can be subclassified further into diagnoses of AERD, allergic fungal rhinosinusitis, or eosinophilic granulomatosis with polyangiitis (EGPA), granulomatous polyangiitis, cystic fibrosis, or primary ciliary dyskinesia. Patients with cystic fibrosis, primary ciliary dyskinesia, and granulomatous polyangiitis were not considered in this clinical guideline. Patients with AERD are the focus of the third management question about ATAD but could also be considered for INCS or biologics. In contrast, patients who do not have AERD are not considered for ATAD but could be candidates for INCS or biologics. Studies in patients with allergic fungal rhinosinusitis and EGPA were included in the clinical guideline, though specific recommendations for patients who fit into these CRSwNP subtypes are not made in this clinical guideline. This clinical guideline is focused around 3 medical management questions: 1 specific to people with AERD, and the other 2 pertinent to all people who have CRSwNP. INCS refer to multiple methods of delivering corticosteroids to the nasal and sinus mucosa. The different delivery modalities depend on the formulation of the drug and the device used to apply it. The types of delivery methods considered in this clinical guideline include nasal spray, rinse (also called flush or irrigation), exhalation delivery system, drops, and stents/dressing. Please see Table E1 in this article’s Online Repository (available at www.jacionline.org) for details about these different delivery methods. Corticosteroid injections were not considered. INCS are self-administered by patients except when a stent or dressing is placed by a clinician with the proper expertise. All INCS delivery methods except for stent/dressing involve a patient using the medicine every day, sometimes more than once. Some delivery methods require manual dexterity and specific head positioning. INCS sprays are available without a prescription while most other forms of INCS require a prescription in the United States. Systemic corticosteroids such as oral tablets or intramuscular injections were not considered for this guideline. Biologics are antibodies derived from organisms by recombinant technology. They are designed to target specific inflammatory pathways thought to be important in disease pathophysiology. Most patients who have CRSwNP have type 2 inflammation, and the biologics considered for people with CRSwNP are designed to modify the type 2inflammatory response. The biologics considered in the clinical guideline target IL-4 and IL-13 (dupilumab), IL-5 (benralizumab, mepolizumab, reslizumab), IgE (omalizumab), Siglec-8 (AK001), and IL-33 (etokimab). Dosing for biologics for CRSwNP varies based on the type of biologic and may be based on weight, laboratory tests, or severity of disease. Biologics require a prescription in the United States and parenteral administration. ATAD is a 2-part process by which patients with AERD are first desensitized to aspirin and then, following desensitization, continued on daily aspirin therapy. During a desensitization, patients are gradually exposed to larger doses of aspirin (≤325 mg) over a period of 1 to 3 days depending on which protocol is used. By definition, patients with AERD frequently develop upper and/or lower respiratory reactions at some point during the desensitization. However, patients who recently underwent sinonasal surgery or who are taking certain other medications may report few to no symptoms during the process. Following the desensitization, patients are then instructed to take aspirin daily. While there is no global consensus as to the specific dose of aspirin needed for treatment of AERD, the available RCTs most commonly used doses between 650 mg and 1300 mg per day. Importantly, aspirin must be taken every day after a desensitization. If a patient misses a dose for >2 days, they must be evaluated by their allergist prior to continuing aspirin therapy and they may have to redo the desensitization procedure. Finally, it should be stressed that the desensitization itself does not provide clinical benefit for patients with AERD but instead the means by which patients with AERD are able to take aspirin daily. Disease-specific quality of life in the trials was measured using different types of standardized and validated questionnaires. The most commonly used tools were the SinoNasal Outcome Test (SNOT) which is a 20-item (SNOT-20) or 22-item (SNOT-22) patient self-administered questionnaire.13Piccirillo J.F. Merritt Jr., M.G. Richards M.L. Psychometric and clinimetric validity of the 20-item Sino-Nasal Outcome Test (SNOT-20).Otolaryngol Head Neck Surg. 2002; 126: 41-47Crossref PubMed Scopus (712) Google Scholar The SNOT-22 scale is from 0 to 110 (total score), with higher scores associated with a worsening impact on disease-specific quality of life. In this guideline, scales other than SNOT-22 were normalized to the SNOT-22 scale using accepted techniques.14Higgins J.P.T. Thomas J. Chandler J. Cumpston M. Li T. Page M.J. Welch V.A. Cochrane Handbook for Systematic Reviews of Interventions. Version 6.3 (updated February 2022). Cochrane, London (UK)2022www.training.cochrane.org/handbookGoogle Scholar The SNOT-22 has a minimally important difference (MID) of 8.9 to 12 points improvement (which would result in a lower score using the total score); the CRSwNP work group selected 8.9 as the a priori MID.15Chowdury N.I. Mace J.C. Bodner T.E. Alt J.A. Deconde A.S. Levy J.M. Smith T.L. Investigating the minimum clinical important difference for SNOT-22 symptom domain in surgical management of chronic rhinosinusitis.Int Forum Allergy Rhinol. 2017; 7: 1149-1155Crossref PubMed Scopus (98) Google Scholar,16Phillips K.M. Hoehle L.P. Caradonna D.S. Gray St Sedaghat A.R. Determinants of noticeable symptom improvement despite sub-MCID changes in SNOT-22 score after treatment for chronic rhinosinusitis.Int Forum Allergy Rhinol. 2019; 9: 508-513Crossref PubMed Scopus (29) Google Scholar This means that a patient whose SNOT-22 score increased more than 9 to 12 points is likely to have a patient-important worsened disease-specific quality of life and that, conversely, a decrease in 9 to 12 points means a patient is likely to have a patient-important improvement in disease-specific quality of life. Nasal symptom scores were patient-reported and could be total nasal symptom scores or nasal obstruction specifically. Multiple scales (eg, 0-3, 0-10, 0-100) were encountered in the trial literature, and for each outcome, the measurement was adjusted to the most commonly used scale for that specific intervention. Because there is no MID reported for nasal symptom scores, the CRSwNP work group, with input from patient participants, set an MID of 0.3 for the 0 to 3 scale and 1.0 for the 0 to 10 scale. Sense of smell was defined both as patient-reported (with various scales, 0-3 being most common) and as objectively measured, with the University of Pennsylvania Smell Identification Test (UPSIT) being the most common test.17Doty R.L. Shaman P. Kimmelman C.P. Dann M.S. University of Pennsylvania Smell Identification Test: a rapid quantitative olfactory function test for the clinic.Laryngoscope. 1984; 94: 176-178Crossref PubMed Scopus (663) Google Scholar Following a discussion within the CRSwNP work group that noted that subjective and objective estimates were consistent, a decision was made to normalize all smell-related outcomes to the UPSIT. The UPSIT is on a scale of 0 to 40, where a higher score translates to a better smell function. Because there is not an MID reported for the UPSIT, the CRSwNP work group, with input from patient participants, set an MID of 4.0 for the 0 to 40 scale. MID thresholds were established or agreed on by the CRSwNP workgroup for the following outcomes for which established MIDs were not available: rescue surgery (5% risk difference); any adverse event (5% risk difference); serious adverse events (1% risk difference); nasal polyp score (0.3 on 0-3 scale or 1.0 on 0-8 scale); nasal endoscopy score (3 on 0-12 modified Lund-Kennedy scale)18Psaltis A.J. Li G. Vaezeafshar R. Cho K.S. Hwang P.H. Modification of the Lund Kennedy endoscopy scoring system improves its reliability and correlates with patient reported outcome measures.Laryngoscope. 2014; 124: 226-229Crossref Scopus (158) Google Scholar; and computed tomography imaging (4 on 0-24 Lund-Mackay imaging scale).19Lund V.J. Mackay I.S. Staging in rhinosinusitis.Rhinology. 1993; 31: 183-184PubMed Google Scholar There were 4 groups who supported the development of this guideline. First, the JTF-PP provided overall oversight of the guideline development with support from their parent organizations, the ACAAI and the AAAAI. Second, a CRSwNP work group consisting of allergy-immunology specialists, otorhinolaryngologists, and methodologists started with Population, Intervention, Comparison, and Outcomes questions; rated the importance of outcomes a priori; assessed prior systematic review and meta-analyses; performed up-to-date searches and systematic review/meta-analyses as needed; led the writing of technical reports; and organized materials in preparation for the guideline panel meeting. Some of the CRSwNP work group members were also JTF-PP members. Third, the guideline panel included members of the CRSwNP work group, 4 patient participants, and 4 researchers with experience in evidence synthesis and guideline development. The 4 patient participants were identified by members of the work group. The guideline panel reviewed information from the work group and formed recommendations and an evidence-to-decision (EtD) framework. Fourth, the Evidence in Allergy group at McMaster University supported the evidence synthesis process and its linkage to decision making. The primary responsibility of the guideline panel was to participate in a virtual meeting where the guideline recommendations were discussed. See Table E2 for a list of the members in each group. The guideline panel developed the recommendations and appraised the certainty of the supporting evidence following the GRADE approach. The overall guideline-development process, including funding of the work, panel formation, management of conflicts of interest, internal and external review, and organizational approval, was guided by the policies and procedures derived from the GIN-McMaster Guideline Development Checklist (https://cebgrade.mcmaster.ca/guidecheck.html) and intended to meet recommendations for trustworthy guidelines by the Institute of Medicine and the GIN. Project oversight was provided by a clinical chair (A.T.P.) and assisted by 2 guideline methodology cochairs (D.K.C. and M.A.R.). The clinical chair (A.T.P.) vetted and appointed individuals to the guideline panel. The methodology cochairs (D.K.C. and M.A.R.) vetted and retained researchers to conduct systematic reviews of evidence and coordinate the guideline-development process, including use of the GRADE approach. The panel’s work was done using Web-based tools: Google Forms (docs.google.com/forms/); GRADEpro Guideline Development Tool (www.gradepro.org); and multiple video-based meetings including a meeting where the entire panel discussed and finalized the recommendations. Development of these guidelines was funded by the JTF-PP, which is financially supported by the ACAAI and AAAAI. Leadership from the ACAAI and AAAAI reviewed and approved the research questions after input from the JTF-PP and the CRSwNP work group. Members of the JTF-PP, CRSwNP work group, and guideline panel received no payments for their work related to this guideline. The JTF-PP funded the technical reports used to support the clinical guideline process.