_Clinical Paper Summary Tool 801-382-001 Rev A.pdf

*Internal Use Only Clinical Paper Summary Guide 801-382-001 Rev A Internal Use Only Contents Efficacy STAR 1-year Strollo 2014 and STAR 5-year Woodson 2018​ 3 ADHERE Registry 6 Efficacy vs Alternatives Heiser 2022 – Efficacy CPAP vs Inspire Huntley 2020 – Inspire efficacy vs traditional slee...

*Internal Use Only Clinical Paper Summary Guide 801-382-001 Rev A Internal Use Only Contents Efficacy STAR 1-year Strollo 2014 and STAR 5-year Woodson 2018​ 3 ADHERE Registry 6 Efficacy vs Alternatives Heiser 2022 – Efficacy CPAP vs Inspire Huntley 2020 – Inspire efficacy vs traditional sleep surgery - ADHERE 8 10 Safety/Cost Nord 2022 – Inspire has a lower risk of complication and readmission than traditional sleep surgery 12 Glossary 14 2 Internal Use Only Efficacy STAR 1-year Strollo 2014 & STAR 5-year Woodson 2018​ Objective Determine safety & efficacy of Inspire by measuring AHI (objective), ODI (objective), FOSQ (subjective), ESS subjective) before & after implant. Results published at 1, 3, and 5 years. Methods (design) • • • • Prospective Pre/post Multi-center 5 yr follow-up Inclusion Criteria AHI 20-50, OSA (not central), AP Collapse, other Conclusion • IDE trial that led to FDA approval of Inspire. • Statistically significant improvement in objective and subjective measures. Median AHI decreased from 29.3 to 6.2 (78% reduction) and Median ESS decreased from 11 to 6 after 5 years follow up. Apnea-Hypopnea Index (AHI) Epworth Sleepiness Scale 35 12 29.3 25 11 10 Median ESS Median AHI (events/hour) 30 20 15 10 9 5 6 6.2 0 Normalized Daytime Sleepiness 8 6 6 6 6 1-Year 3-Year 5-Year 4 2 0 Baseline 1-Year 3-Year 5-Year Baseline 3 Internal Use Only Detailed Results *P-Value comparing Baseline to Month 12 is <.001 | **Consistent results at Month 36 and Month 60 Outcome Measure AHI (Objective) ESS (Subjective) Baseline Month 12* Month 36** n 126 124 98 71 Median 29.3 9 6 6.2 n 126 123 113 92 11 6 6 6 n 126 124 98 71 Median 25.4 7.4 4.8 4.6 n 126 123 113 92 Median 14.6 18.2 18.8 18.7 Median ODI (4%) (Objective) FOSQ (Subjective) Month 60** Common Objection Answer: Median Average was used instead of Mean Average to reduce impact of outliers with extreme values. 126 Underwent Implantation 1 died device unrelated to cardiac event 1 non-responder elective device removal 12 Month 124 Included 1 responder non-elective device removal due to septic arthritis 24 Month 123 Included 36 Month 116 Included 1 died from cardiac arrest following blunt chest trauma 1 died from homicide 1 non-responder device removal 4 lost to follow up 2 lost to follow up 1 discontinued therapy 5 site closure 48 Month 60 Month 109 Included 97 Included 1 died multiple myeloma 1 died myelodysplastic syndrome 6 lost to follow up 3 discontinued therapy 71 with voluntary polysomnograms Common Objection Answer: Explanation why we started with 126 patients, down to 92 after 5yrs. Of the 92, 71 patients volunteered to do a PSG. 4 Internal Use Only Apnea-Hypopnea Index Oxygen Desaturation Index Therapy-maintenance group (N=23) Therapy-withdrawal group (N=23) Score (events/hour) 30 31.3 35 30.1 30 25.8 25 Score (events/hour) 35 Therapy-maintenance group (N=23) Therapy-withdrawal group (N=23) 20 15 8.9 7.6 7.2 10 25 23.0 15 10 5 0 0 Month 12 26.8 20 5 Baseline 26.7 Randomized, therapy-withdrawal trial 6.3 Baseline 6.0 Month 12 8.0 Randomized, therapy-withdrawal trial Common Objection Answer: Therapy was randomly turned off for ≥5 days prior to PSG in patients who met the Sher Criteria, to verify it was not a placebo effect. Strollo 1 yr. STAR 5-year Upper Airway Stimulation for Obstructive Sleep Apnea: 5-Year Outcomes View on ShowPad Share to MD (Paywall) STAR 1-year Pivotal Trial Upper-Airway Stimulation for Obstructive Sleep Apnea View on ShowPad Share to MD (Open Access) Next Study: ADHERE Registry 5 Internal Use Only Efficacy ADHERE Registry Objective Started October 2016, with 61 centers in the US and EU. Updated database of “real-world” Inspire clinical outcomes. Data collected includes: demographics, satisfaction, and outcomes. Registry limit reached at 5,000 patients as of July 2023. As of May 2021, 1,170 completed 1yr follow-up, results published June 2022. Multiple ADHERE publications are available which provide an update to the patient satisfaction and efficacy data overall. Additionally, each publication analyzes the ADHERE data set to provide answers to important questions related to OSA and Inspire therapy using real-world data. Methods (design) Inclusion Criteria • Registry • International Multi-center • 1-year follow-up Anyone implanted with Inspire at participating centers Conclusion Treatment Goals & Expectations: Real world results from the ADHERE Registry. Untreated OSA Inspire 33/hr 10.2/hr Symptom Relief (ESS) 11 6 Therapy Usage (Objective) — 5.7 hrs/night Patient Satisfaction (Survey) — 90% (Baseline) Disease Burden (AHI) (12 mo.) The ADHERE Registry: • • • • • Real-world clinical outcomes Global (US/EU) 5,000 patients enrolled 61 medical centers 12-month follow-up Experience of Care: Patients are satisfied with Inspire 91% 92% 93% 90% of patients said Inspire was better than CPAP of patients said they would choose Inspire again of patients said they would recommend Inspire to a friend or family member of patients said they were satisfied with Inspire 6 Internal Use Only Detailed Results Each study derived from the registry will have its own findings. 1,170 69% 11 to 6 5.7 N for our satisfation results Reduction of median average AHI improvement from 33 to 10.2 (N=890) Median average ESS improvement (N=994) Mean usage hrs/ night (N=913) Common Objection Answer: This is 1yr data, the Woodson STAR 5 yr paper provides longer-term data and with SleepSync you will be able to track your patient’s outcomes long-term. Most Recent Adhere Based Publication: Bosschieter 2022 Similar effect of hypoglossal nerve stimulation for obstructive sleep apnea in 5 disease severity categories View on ShowPad Share to MD (Open Access) Next Study: Heiser 2022 - Efficacy & Usage or CPAP Compared to Inspire 7 Internal Use Only Efficacy vs Alternatives Heiser 2022 - Efficacy & Usage of CPAP Compared to Inspire Objective Compare AHI, ESS, and usage to determine efficacy of CPAP vs Inspire Inclusion Criteria Methods (design) • • • • For Inspire Patients: non-adherent to CPAP; For both CPAP and Inspire Patients: diagnosed with moderate to severe OSA; BMI ≤35; ESS >11; using treatment for >1-yr Retrospective Multi-center Mean disease alleviation (MDA) Propensity score matching Conclusion • Re-Frame the conversation as Inspire vs untreated OSA • Inspire for CPAP intolerant patients is as effective as CPAP compliant patients & averaged 1 hr more usage per tnight • This is a German study but has been studied 2 times before at the Cleveland Clinic with similar findings. (Studies linked at the bottom of the section) Detailed Results Propensity Matched: Patients in this study were compared to other patients which were similar in age, AHI, and BMI. Variable HNS (N=63) PAP (N=63) P-Value AHI ESS AHI ESS AHI ESS Baseline � SD 33.9 � 15.1 15.4 � 3.5 36.8 � 21.6 14.6 � 3.9 0.146 0.050 12-mo FU � SD 8.1 � 6.3 7.5 � 4.7 6.6 � 8.0 10.8 � 5.6 -- 0.268 Reduction � SD 25.8 8.0 � 5.1 30.2 3.9 � 6.8 -- 0.042 <0.001 <0.001 <0.001 0.056 -- -- (Baseline vs. 12-mo FU) Usage � SD (hrs/night) 5.04 � 2.58 4.03 � 2.12 0.087 Common Objection Answer: We should not compare Inspire to PAP, Inspire is for patients who failed PAP. We are talking about patients you saw years ago and never came back or tried several masks and still cannot find a solution. 8 Internal Use Only The result in the table and graph below are summarized for the propensity matched group. The graph shown below differs in the paper because it shows the results for the full group of patients and not for the propensity matched group. However, the propensity matched results are consistent with the results presented in table 4 and the author used the propensity matched results in the results paragraph at the start of the paper. HNS PAP 100% 100% 82% Therapy Efficiency (%) Therapy Efficiency (%) 76% 50% MDA = 59% ((33.9-8.1)/(33.9)) * (5.04/6.5) 78% 0% 50% 100% 50% MDA = 51% ((36.8-6.6)/(36.8)) * (4.03/6.5) 62% 0% Adjusted Adherence (%) 50% 100% Adjusted Adherence (%) Mean Disease Alleviation (MDA) = Therapy efficacy x Adjusted adherence Therapy Efficacy = AHI Reduction/Baseline AHI Adjusted adherence = usage hrs per night / 6.5 6.5 hrs = average sleep time in western industrialized countries Heiser 2022 Related Studies Hypoglossal nerve stimulation versus PAP therapy for OSA Pascoe - JAMA Oto 2022 - Inspire vs PAP View on ShowPad View on ShowPad (Open Access) Share to MD (Open Access) Share to MD Walia et al. - 2020 - Inspire vs PAP View on ShowPad Share to MD (Paywall) Next Study: Huntley 2020 9 Internal Use Only Efficacy vs Alternatives Huntley 2020 - Inspire efficacy vs traditional sleep surgery - ADHERE Objective Compare traditional single and multilevel sleep surgery to Inspire (UAS). Methods (design) Inclusion Criteria • Case control • Retrospective • International multi-center Selected patients that would have met Inspire Criteria (AHI 15-65, BMI <35, and no CCC) but underwent single or multilevel sleep surgery and compared to Inspire patients. Conclusion • Inspire had better AHI reduction and comparable ESS reduction. • Inspire is less invasive and does not change anatomy. Detailed Results Procedure Age (Years) Gender Mean ± SD (n) (% Male) Airway Surgery Inspire (UAS) P-Value 46.1 ± 11.8 59.5 ± 10.8 <.001 88% 83% Baseline AHI Mean ± SD (n) 35.0 ± 13.1 (233) 35.5 ± 15.0 (465) 0.88 Final AHI (12 Mo) Mean ± SD (n) 19.3 + −16.3 (196) 14.1 + −14.4 (465) <.001 AHI Change Mean ± SD (n) −15.9 + −17.3 (196) −21.4 + − 17.8 (465) <.001 Baseline ESS Mean ± SD (n) 11.3 ± 5.1 (233) 11.9 ± 5.5 (465) 0.22 Final ESS (12 Mo) Mean ± SD (n) 5.9 + − 4.0 (129) 7.3 + −4.7 (415) 0.01 ESS Change Mean ± SD (n) −5.8 + − 5.2 (124) −4.7 + −5.2 (388) 0.06 Common Objection Answer: Unlike other sleep surgeries, the patient always returns to the managing physician and it does not change anatomy. 10 Internal Use Only Huntley 2020 Comparison of Traditional Upper Airway Surgery and Upper Airway Stimulation for OSA View on ShowPad Share to MD (Paywall) Next Study: Nord 2022 11 Internal Use Only Safety/Cost Nord 2022 - Comparison of readmission & complication rates between traditional sleep surgery & hypoglossal nerve stimulation Objective Compare readmission & complication rates between Inspire and traditional sleep surgery 90-days postoperatively using electronic health records; controlling for differences in patient populations. Methods (design) • Retrospective • Multi-center • Propensity score matching Inclusion Criteria Primary diagnosis of OSA; ≥22 yrs old; had Inspire, palate, or multilevel surgery Conclusion • Patients in this study were compared to other patients which were similar. For examples similar or the same: age, race, gender, BMI. • Inspire has a lower risk of complication and readmission than traditional sleep surgery. Readmissions & Complication rates of Sleep Surgeries 25% 20% 20% 15% 10% 12% 21% 12% 5% 4% 0% 3% Readmissions 12 Palatal surgery Complications Multilevel surgery Internal Use Only UAS (Inspire) Detailed Results Cohort (n) 90 Days readmissions (% risk) 90 Days complications (% risk) HNS 1014 35 (3.5%) 23 (2.3%) Palate 1014 118 (11.6%) 204 (20.1%) HNS 374 15 (4%) 10 (3%) Multilevel 374 45 (12%) 79 (21%) Procedure HNS vs. Palate HNS vs. Multilevel Common Objection Answer: Difference in the number of patients compared between the palate and multilevel groups is due to the ability to match patients with similar HNS patients. Nord 2022 Comparison of readmission and complication rates between traditional sleep surgery and hypoglossal nerve stimulation View on ShowPad Share to MD (Open Access) Next: Glossary 13 Internal Use Only Glossary a. Prospective: Refers to a study or research design in which data is collected in the present and followed up on in the future. For example, a prospective study may involve enrolling a group of people and tracking their health outcomes over several years to observe the development of a particular disease. b. Pre/post: Describes a comparison made before and after a particular event or intervention. For instance, a pre/ post evaluation may assess the effectiveness of a new exercise program by measuring participants’ fitness levels before they start the program and again after a few months of training. c. Multi-center / Single-center: These terms relate to the number of locations involved in a study. Multi-center means that data is collected from multiple hospitals or research centers, while single-center indicates that data is collected from a single hospital or research center. For example, a multi-center clinical trial might involve several hospitals recruiting patients for a study, while a single-center study would involve only one hospital. d. Statistically significant: Refers to a finding or result that is unlikely to have occurred by chance. Statistical significance is determined by analyzing the data using statistical methods. For example, if a study comparing two treatments shows that the difference in outcomes between the two groups is statistically significant, it suggests that the difference is unlikely to be due to random variation. e. P-value: It is a statistical measure used to determine the likelihood of obtaining a result as extreme as the one observed, assuming there is no true effect or difference. A p-value less than a predetermined threshold (usually 0.05) is often considered statistically significant. For example, a study may report a p-value of 0.03, indicating that there is a 3% chance of obtaining the observed result by chance alone. f. Clinically significant: Refers to a finding or result that is considered meaningful or important from a medical or clinical perspective. It relates to whether the observed effect or difference has practical implications for patient care. For example, a new drug might be deemed clinically significant if it significantly reduces the symptoms of a disease and improves patients’ quality of life. g. N or n: It represents the sample size in a study, referring to the number of participants or observations included in the analysis. For example, if a study reports an “N of 100,” it means that 100 individuals were included in the study. h. Averages: Mean vs Median: Mean is the arithmetic average, calculated by adding up all the values in a set and dividing by the number of values. Median is the middle value in a set when arranged in numerical order. For example, if we have the set of numbers 2, 4, 6, 8, and 10, the mean is 6 (sum of all values divided by 5), and the median is also 6 (middle value in the ordered set). i. ± SD or Standard Deviation: It is a measure of the variability or spread of a set of values. It quantifies how much the values differ from the mean average. The symbol ± SD indicates the mean value plus or minus the standard deviation. For example, a study might report a mean age of 40 ± 5 years, which means the average age is 40 years, with a standard deviation of 5 years. j. IQR: It stands for Interquartile Range, which measures the spread of a dataset by calculating the difference between the first quartile (25th percentile) and the third quartile (75th percentile). It provides a measure of the dispersion of the middle 50% of the data. For example, if the IQR of a set of scores is 10, it means that the range between the 25th and 75th percentiles is 10. k. Open Access vs Paywall: Open Access refers to unrestricted access to research articles and publications, allowing anyone to read, download, and share them freely. Paywall, on the other hand, refers to content that is accessible only to those who have paid a fee or have a subscription. l. Inclusion criteria: These are the specific characteristics or criteria that individuals must possess to be eligible for participation in a study. Inclusion criteria are defined to ensure that the study population represents the target population of interest. For example, a study on diabetes treatment might require participants to have a certain age, specific blood glucose levels, and no other underlying medical conditions. 14 Internal Use Only m. Real-world vs protocol data: Real-world data refers to information collected from routine clinical practice, reflecting how treatments and interventions are used in real-life settings. Protocol data, on the other hand, refers to data collected in a controlled and structured manner following a predetermined study protocol. Realworld data provides insights into how treatments work in everyday scenarios, while protocol data is gathered under controlled conditions to evaluate specific hypotheses. n. Subjective vs objective: Subjective refers to opinions or judgments based on personal experiences or perspectives. Objective refers to information or measurements based on facts, evidence, or measurable criteria. For example, sleepiness reported by a patient is subjective, as it is based on their personal perception, AHI measured with a device is objective, as it is based on numerical readings. o. AHI: Stands for Apnea-Hypopnea Index. AHI is a measure used in sleep medicine to assess the severity of sleep apnea. It quantifies the number of apneas (complete pauses in breathing) and hypopneas (partial reductions in airflow) per hour of sleep. A higher AHI score indicates a greater degree of sleep-disordered breathing. p. ESS: It stands for Epworth Sleepiness Scale. ESS is a self-reported questionnaire used to measure daytime sleepiness and assess the likelihood of falling asleep in various situations. It consists of eight questions with a scoring system that helps evaluate the severity of daytime sleepiness. q. FOSQ: It stands for Functional Outcomes of Sleep Questionnaire. FOSQ is a questionnaire used to evaluate the impact of sleep disorders on a person’s daily functioning and quality of life. It assesses factors such as vigilance, social interactions, intimacy, general productivity, and overall well-being. r. ODI: It stands for Oxygen Desaturation Index. ODI measures the frequency of significant drops in blood oxygen levels during sleep, particularly in relation to sleep apnea. It calculates the number of times per hour that blood oxygen saturation drops by a certain percentage. s. Propensity score matching: Is a statistical technique used in observational studies to reduce bias and mimic the random assignment of participants in a controlled trial. Propensity score matching involves creating a score that estimates the likelihood of an individual receiving a particular treatment, and then matching individuals with similar scores between treatment and control groups. t. Palate surgery: Refers to surgical procedures that involve the modification or reconstruction of the palate, which is the roof of the mouth. Palate surgery is often performed to treat conditions such as sleep apnea, cleft palate, or certain snoring disorders. u. Multilevel surgery: Refers to a surgical approach that involves targeting multiple levels or anatomical structures during a procedure. For example, in the context of sleep surgery, multilevel surgery may involve addressing obstructions in the nose, palate, and base of the tongue simultaneously. v. Case control: A type of observational study design that compares individuals with a particular condition or disease (cases) to individuals without the condition (controls). Case-control studies are often used to identify factors associated with the development of a disease by comparing the characteristics or exposures of cases and controls. w. Mean disease alleviation (MDA): MDA is a measure used in clinical trials to quantify the average improvement or reduction in disease symptoms or severity experienced by participants. It calculates the mean change in a particular outcome measure between baseline and follow-up assessments. x. SHER 15/20 Criteria: SHER 15/20 criteria is used by surgeons to evaluate the success of an intervention: a minimum of 50% reduction in AHI with a final AHI less than 15/20. 15 Internal Use Only