Clinical dose rationale of tislelizumab in patients with solid or hematological advanced tumors.

Tislelizumab, an anti-programmed cell death protein 1 monoclonal antibody, has demonstrated improved survival benefits over standard of care for multiple cancer indications. We present the clinical rationale and data supporting tislelizumab dose recommendation in patients with advanced tumors. The phase I, first-in-human, dose-finding BGB-A317-001 study (data cutoff [DCO]: August 2017) examined the following tislelizumab dosing regimens: 0.5-10 mg/kg every 2 weeks (q2w), 2-5 mg/kg q2w or q3w, and 200 mg q3w. Similar objective response rates (ORRs) were reported in the 2 and 5 mg/kg q2w or q3w cohorts. Safety outcomes (grade ≥3 adverse events [AEs], AEs leading to dose modification/discontinuation, immune-mediated AEs, and infusion-related reactions) were generally comparable across the dosing range examined. These results, alongside the convenience of a fixed q3w dose, formed the basis of choosing 200 mg q3w as the recommended dosing regimen for further clinical use. Pooled exposure-response (E-R) analyses by logistic regression using data from study BGB-A317-001 (DCO: August 2020) and three additional phase I/II studies (DCOs: 2018-2020) showed no statistically significant correlation between tislelizumab pharmacokinetic exposure and ORR across multiple solid tumor types or classical Hodgkin's lymphoma, nor was exposure associated with any of the safety end points evaluated over the dose range tested. Hence, tislelizumab showed a relatively flat E-R relationship. Overall, the totality of data, including efficacy, safety, and E-R analyses, together with the relative convenience of a fixed q3w dose, provided clinical rationale for the recommended dosing regimen of tislelizumab 200 mg q3w for multiple cancer indications.

Evaluation of omadacycline dosing regimens in Chinese using population pharmacokinetic-pharmacodynamic analysis.

PURPOSE: Omadacycline (PTK-0796) is a first-in-class aminomethylcycline for adult patients with community-acquired bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible pathogens. We investigated the pharmacokinetic (PK) and pharmacodynamic (PD) profile of omadacycline, considering the impact of covariates, particularly ethnicity, on PK and determined the PK/PD cutoff values for dosing regimens. METHODS: Utilizing nonlinear mixed-effects modeling, we pooled data from 11 clinical trials for PopPK analysis. The first-order conditional estimation with interaction (FOCEI) method in NONMEM facilitated model parameter estimation. Employing a stepwise model selection strategy, with forward addition (P < 0.01) and backward deletion (P < 0.001), we assessed the potential impacts of covariates on omadacycline PK, including baseline age, body weight, sex, race, body mass index, body surface area, baseline albumin, creatine clearance, and formulation. After validating the model through various methods, the final PopPK model underwent Monte Carlo simulations to generate the PK profile for the Chinese population. This enabled AUC calculation and assessment of the probability of target attainment (PTA) and the cumulative fraction of response (CFR) for various dosing regimens and bacterial strains. RESULTS: Omadacycline's PK can be adequately characterized by a three-compartment model. Body weight, sex, race, and drug formulation statistically influenced its PK. Asians and non-Asians exhibit similar exposure after intravenous infusion, but oral dosing results in much higher exposures than in non-Asians. Monte Carlo simulation indicates that IV-only or IV/PO sequential therapy regimens provide adequate attainment for all major pathogens causing ABSSSI and CABP. PK/PD cutoffs were generally above the MIC90 value of recent clinical isolates from China. CONCLUSIONS: In conclusion, the approved regimen for China achieved adequate target attainment for all pathogens typically associated with these infections. The higher oral exposure observed in Asians may enhance efficacy without affecting safety or tolerability.

Characterization of Higher Order Structural Changes of a Thermally Stressed Monoclonal Antibody via Mass Spectrometry Footprinting and Other Biophysical Approaches.

Characterizing changes in the higher order structure (HOS) of monoclonal antibodies upon stressed conditions is critical to gaining a better understanding of the product and process. One single biophysical approach may not be best suited to assess HOS comprehensively; thus, the synergy from multiple, complementary approaches improves characterization accuracy and resolution. In this study, we employed two mass spectrometry (MS )-based footprinting techniques, namely, fast photochemical oxidation of proteins (FPOP)-MS and hydrogen-deuterium exchange (HDX)-MS, supported by dynamic light scattering (DLS), differential scanning calorimetry (DSC), circular dichroism (CD), and nuclear magnetic resonance (NMR) to study changes to the HOS of a mAb upon thermal stress. The biophysical techniques report a nuanced characterization of the HOS in which CD detects no changes to the secondary or tertiary structure, yet DLS measurements show an increase in the hydrodynamic radius. DSC indicates that the stability decreases, and chemical or conformational changes accumulate with incubation time according to NMR. Furthermore, whereas HDX-MS does not indicate HOS changes, FPOP-MS footprinting reveals conformational changes at residue resolution for some amino acids. The local phenomena observed with FPOP-MS indicate that several residues show various patterns of degradation during thermal stress: no change, an increase in solvent exposure, and a biphasic response to solvent exposure. All evidences show that FPOP-MS efficiently resolves subtle structural changes and novel degradation pathways upon thermal stress treatment at residue-level resolution.

Enhanced recovery after surgery, current, and future considerations in head and neck cancer.

Objectives: Review of the current and relevant literature to develop a list of evidence-based recommendations that can be implemented in head and neck surgical practices. To provide rationale for the multiple aspects of comprehensive care for head and neck surgical patients. To improve postsurgical outcomes for head and neck surgical patients. Methods: Extensive review of the medical literature was performed and relevant studies in both the head and neck surgery and other surgical specialties were considered for inclusion. Results: A total of 18 aspects of perioperative care were included in this review. The literature search included 276 publications considered to be the most relevant and up to date evidence. Each topic is concluded with recommendation grade and quality of evidence for the recommendation. Conclusion: Since it's conception, enhanced recovery after surgery (ERAS) protocols have continued to push for comprehensive and evidence based postsurgical care to improve patient outcomes. Head and neck oncology is one of the newest fields to develop a protocol. Due to the complexity of this patient population and their postsurgical needs, a multidisciplinary approach is needed to facilitate recovery while minimizing complications. Current and future advances in head and neck cancer research will serve to strengthen and add new principles to a comprehensive ERAS protocol. Level of Evidence: 2a.

Co-developed implementation guidelines to maximize acceptability, feasibility, and usability of mobile phone supervision in Kenya.

Opportunities exist to leverage mobile phones to replace or supplement in-person supervision of lay counselors. However, contextual variables, such as network connectivity and provider preferences, must be considered. Using an iterative and mixed methods approach, we co-developed implementation guidelines to support the implementation of mobile phone supervision with lay counselors and supervisors delivering a culturally adapted trauma-focused cognitive behavioral therapy in Western Kenya. Guidelines were shared and discussed with lay counselors in educational outreach visits led by supervisors. We evaluated the impact of guidelines and outreach on the acceptability, feasibility, and usability of mobile phone supervision. Guidelines were associated with significant improvements in acceptability and usability of mobile phone supervision. There was no evidence of a significant difference in feasibility. Qualitative interviews with lay counselors and supervisors contextualized how guidelines impacted acceptability and feasibility - by setting expectations for mobile phone supervision, emphasizing importance, increasing comfort, and sharing strategies to improve mobile phone supervision. Introducing and discussing co-developed implementation guidelines significantly improved the acceptability and usability of mobile phone supervision. This approach may provide a flexible and scalable model to address challenges with implementing evidence-based practices and implementation strategies in lower-resourced areas.

Application of NMR and Chemometric Analyses to Better Understand the Quality Attributes in pH and Thermally Degraded Monoclonal Antibodies.

PURPOSE: Nuclear magnetic resonance (NMR) spectroscopy provides the sensitivity and specificity to probe the higher order structure (HOS) of monoclonal antibodies (mAbs) for potential changes. This study demonstrates an application of chemometric tools to measure differences in the NMR spectra of mAbs after forced degradation relative to the respective unstressed starting materials. METHODS: Samples of adalimumab (Humira, ADL-REF) and trastuzumab (Herceptin, TRA-REF) were incubated in three buffer-pH conditions at 40°C for 4 weeks to compare to a control sample that was left unstressed. Replicate 1D 1H and 2D 1H-13C HMQC NMR spectra were collected on all samples. Chemometric analyses such as Easy Comparability of HOS (ECHOS), PROtein FIngerprinting by Lineshape Enhancement (PROFILE), and Principal Component Analysis (PCA) were applied to capture and quantitate differences between the spectra. RESULTS: Visual and statistical inspection of the 2D 1H-13C HMQC spectra of adalimumab and trastuzumab after forced degradation conditions shows no changes in the spectra relative to the unstressed material. Chemometric analysis of the 1D 1H NMR spectra shows only minor changes in the spectra of adalimumab after forced degradation, but significant differences in trastuzumab. CONCLUSION: The chemometric analyses support the lack of statistical differences in the structure of pH-thermal stressed adalimumab, however, it reveals conformational changes or chemical modifications in trastuzumab after forced degradation. Application of chemometrics in comparative NMR studies enables HOS characterization and showcases the sensitivity and specificity in detecting differences in the spectra of mAbs after pH-thermal forced degradation with respect to local and global protein structure.

The combined use of DTI and MR elastography for monitoring microstructural changes in the developing brain of a neurodevelopmental disorder model: Poly (I:C)-induced maternal immune-activated rats.

Early neuropathology mechanisms in neurodevelopmental disorders are partially understood because routine anatomical magnetic resonance imaging (MRI) cannot detect subtle brain microstructural changes in vivo during postnatal development. Therefore, we investigated the potential value of magnetic resonance elastography (MRE) and diffusion tensor imaging (DTI) in a rat model of neurodevelopmental disorder induced by maternal immune activation. We studied 12 offspring of mothers injected with polyriboinosinic-polyribocytidylic acid (poly (I:C), 4 mg/kg) on gestational day 15, plus 8 controls. T2-weighted anatomical MR images, MRE (800 Hz) and DTI (30 gradient directions, b = 765.8 s/mm2, 5 images, b = 0 s/mm2) were collected when the rats were 4 and 10 weeks old, and results were compared with histological analysis performed at week 10. Ventricles were ~1.4 fold larger from week 4 in poly (I:C) rats than in controls. No other morphological abnormalities were detected in poly(I:C) rats. At week 4, larger ventricles were correlated with lower external capsule fractional anisotropy and internal capsule radial diffusion (Pearson, r = -0.53, 95% confidence intervals (CI) [-0.79 to -0.12], and r = -0.45, 95% CI [-0.74 to -0.01], respectively). The mean and radial diffusion of the corpus callosum, the mean and axial diffusion of the internal capsule and the radial diffusion properties in the external capsule increased with age for poly (I:C) rats only (Sidak's comparison, P<0.05). Cortical stiffness did not increase with age in poly (I:C) rats, in contrast with controls (Sidak's comparison, P = 0.005). These temporal variations probably reflected abnormal myelin content, decreased cell density and microglia activation observed at week 10 after histological assessment. To conclude, MRE and DTI allow monitoring of abnormal brain microstructural changes in poly (I:C) rats from week 4 after birth. This suggests that both imaging techniques have the potential to be used as complementary imaging tools to routine anatomical imaging to assist with the early diagnosis of neurodevelopmental disorders and provide new insights into neuropathology.

Pharmacokinetics of Novel Furoxan/Coumarin Hybrids in Rats Using LC-MS/MS Method and Physiologically Based Pharmacokinetic Model.

Novel furoxan/coumarin hybrids were synthesized, and pharmacologic studies showed that the compounds displayed potent antiproliferation activities via downregulating both the phosphatidylinositide 3-kinase (PI3K) pathway and the mitogen-activated protein kinase (MAPK) pathway. To investigate the preclinical pharmacokinetic (PK) properties of three candidate compounds (CY-14S-4A83, CY-16S-4A43, and CY-16S-4A93), liquid chromatography, in tandem with the mass spectrometry LC-MS/MS method, was developed and validated for the simultaneous determination of these compounds. The absorption, distribution, metabolism, and excretion (ADME) properties were investigated in in vitro studies and in rats. Meanwhile, physiologically based pharmacokinetic (PBPK) models were constructed using only in vitro data to obtain detailed PK information. Good linearity was observed over the concentration range of 0.01−1.0 µg/mL. The free drug fraction (fu) values of the compounds were less than 3%, and the clearance (CL) values were 414.5 ± 145.7 mL/h/kg, 2624.6 ± 648.4 mL/h/kg, and 500.6 ± 195.2 mL/h/kg, respectively. The predicted peak plasma concentration (Cmax) and the area under the concentration-time curve (AUC) were overestimated for the CY-16S-4A43 PBPK model compared with the experimental ones (fold error > 2), suggesting that tissue accumulation and additional elimination pathways may exist. In conclusion, the LC-MS/MS method was successively applied in the preclinical PK studies, and the detailed information from PBPK modeling may improve decision-making in subsequent new drug development.

Model-based population pharmacokinetic analysis of tislelizumab in patients with advanced tumors.

Tislelizumab, a humanized immunoglobulin G4 monoclonal antibody, is a programmed cell death protein 1 (PD-1) inhibitor designed to minimize Fc gamma receptor binding on macrophages to limit antibody-dependent phagocytosis, a potential mechanism of resistance to anti-PD-1 therapy. The pharmacokinetic (PK) profile of tislelizumab was analyzed with population PK modeling using 14,473 observed serum concentration data points from 2596 cancer patients who received intravenous (i.v.) tislelizumab at 0.5-10 mg/kg every 2 weeks or every 3 weeks (q3w), or a 200 mg i.v. flat dose q3w in 12 clinical studies. Tislelizumab exhibited linear PK across the dose range tested. Baseline body weight, albumin, tumor size, tumor type, and presence of antidrug antibodies were identified as significant covariates on central clearance, whereas baseline body weight, sex, and age significantly affected central volume of distribution. Sensitivity analysis showed that these covariates did not have clinically relevant effects on tislelizumab PK. Other covariates evaluated, including race (Asian vs. White), lactate dehydrogenase, estimated glomerular filtration rate, renal function categories, hepatic function measures and categories, Eastern Cooperative Oncology Group performance status, therapy (monotherapy vs. combination therapy), and line of therapy did not show a statistically significant impact on tislelizumab PK. These results support the use of tislelizumab 200 mg i.v. q3w without dose adjustment in a variety of patient subpopulations.

Otolaryngology consultations for COVID-19 patients: A retrospective cohort study of indications, interventions, and considerations.

OBJECTIVE: To identify differences in inpatient otolaryngology consultations and interventions for patients based on COVID-19. METHODS: Records were reviewed for all patients for whom otolaryngology was consulted at a high-volume tertiary care hospital from April 30, 2020 to October 1, 2020. Demographic information, length of stay, COVID-19 status, indication for consultation, and otolaryngology interventions were recorded. Statistical analysis was performed using R software. RESULTS: Bleeding composed a significantly higher proportion of otolaryngology consults in COVID-19 positive patients (28% vs. 8.4%, p<0.0001). Management of bleeding was the most common procedure performed in positive patients (n=37, 35%), and they had a higher median number of interventions performed when compared to bleeding patients who tested negative (1, IQR 1-2 vs. 1, IQR 0-1, p=0.04). COVID-19 positive patients with bleeding were more likely to expire than those with other indications for otolaryngology consultation (50% vs. 7%, p<0.001). CONCLUSION: Bleeding and associated interventions comprised the predominant discrepancy between COVID-19 positive and negative patients in our cohort. We encourage routine use of simple and cost-effective methods to decrease risk of bleeding.

FIBCD1 is an endocytic GAG receptor associated with a novel neurodevelopmental disorder.

Whole-exome sequencing of two patients with idiopathic complex neurodevelopmental disorder (NDD) identified biallelic variants of unknown significance within FIBCD1, encoding an endocytic acetyl group-binding transmembrane receptor with no known function in the central nervous system. We found that FIBCD1 preferentially binds and endocytoses glycosaminoglycan (GAG) chondroitin sulphate-4S (CS-4S) and regulates GAG content of the brain extracellular matrix (ECM). In silico molecular simulation studies and GAG binding analyses of patient variants determined that such variants are loss-of-function by disrupting FIBCD1-CS-4S association. Gene knockdown in flies resulted in morphological disruption of the neuromuscular junction and motor-related behavioural deficits. In humans and mice, FIBCD1 is expressed in discrete brain regions, including the hippocampus. Fibcd1 KO mice exhibited normal hippocampal neuronal morphology but impaired hippocampal-dependent learning. Further, hippocampal synaptic remodelling in acute slices from Fibcd1 KO mice was deficient but restored upon enzymatically modulating the ECM. Together, we identified FIBCD1 as an endocytic receptor for GAGs in the brain ECM and a novel gene associated with an NDD, revealing a critical role in nervous system structure, function and plasticity.

Dermatologic toxicities of targeted antineoplastic agents and immune checkpoint inhibitor therapy in pediatric patients: A systematic review.

Cutaneous adverse events (cAEs) from targeted antineoplastic agents and immune checkpoint inhibitors are common in children with cancer and may lead to dose reduction or cessation of critical oncologic treatment. Timely diagnosis and proper management of cAEs in pediatric oncology patients is essential to optimize ongoing cancer-directed therapy and improve quality of life. This systematic review of published studies summarizes dermatologic toxicities to targeted anticancer treatments and immune checkpoint inhibitors.

Covariate effects and population pharmacokinetic analysis of the anti-FGFR2b antibody bemarituzumab in patients from phase 1 to phase 2 trials.

PURPOSE: A population pharmacokinetic (PK) analysis of the anti-fibroblast growth factor receptor 2b antibody, bemarituzumab, was performed to evaluate the impact of covariates on the PK and assess whether dose adjustment is necessary for a future phase 3 trial. METHODS: Serum concentration data were obtained from three clinical trials, with 1552 bemarituzumab serum samples from 173 patients, and were analyzed using nonlinear mixed-effects modeling. RESULTS: A two-compartment model with parallel linear and nonlinear (Michaelis-Menten) elimination from the central compartment best described the bemarituzumab serum concentration data. The final model estimated a typical linear clearance (CL) of 0.311 L/day, volume of distribution in the central compartment (Vc) of 3.58 L, distribution clearance (Q) of 0.952 L/day, volume of distribution in the peripheral compartment (Vp) of 2.71 L, maximum drug elimination by nonlinear clearance (Vmax) of 2.80 µg/day, and Michaelis-Menten constant (Km) of 4.45 µg/mL. Baseline body weight, baseline albumin, gender, and chemotherapy were identified as statistically significant covariates on the PK of bemarituzumab. Given the low interindividual variability of bemarituzumab key PK parameters (CL and Vc) and the small or modest effect of all statistically significant covariates on bemarituzumab exposure at steady-state, no covariate is expected to have clinically meaningful effects on bemarituzumab exposure. CONCLUSION: No covariate had a clinically meaningful impact on bemarituzumab exposure. These results indicate that dose adjustment of bemarituzumab is not necessary, based on the aforementioned covariates, for a future phase 3 trial in gastric and gastroesophageal junction adenocarcinoma population with FGFR2b overexpression in combination with mFOLFOX6.

The Development of the Rheumatology Informatics System for Effectiveness Learning Collaborative for Improving Patient-Reported Outcome Collection and Patient-Centered Communication in Adult Rheumatology.

OBJECTIVE: Patient-reported outcomes (PROs) are an integral part of treat-to-target approaches in managing rheumatoid arthritis (RA). In clinical practice, however, routine collection, documentation, and discussion of PROs with patients are highly variable. The RISE LC (Rheumatology Informatics System for Effectiveness Learning Collaborative) was established to develop and share best practices in PRO collection and use across adult rheumatology practices in the United States METHODS: The goals of the RISE LC were developed through site surveys and in-person meetings. Participants completed a baseline survey on PRO collection and use in their practices. RISE LC learning sessions focused on improving communication around PROs with patients and enhancing shared decision-making in treatment plans. During the coronavirus disease 2019 (COVID-19) pandemic, the RISE LC pivoted to adapt PRO tools for telehealth. RESULTS: At baseline, all responding sites (n = 15) had established workflows for collecting PROs. Most sites used paper forms alone. PRO documentation in electronic health records was variable, with only half of the sites using structured data fields. To standardize and improve the use of PROs, participants iteratively developed a Clinical Disease Activity Index-based RA Disease Activity Communication Tool to solicit treatment goals and improve shared decision-making across sites. The COVID-19 pandemic necessitated developing a tool to gauge PROs via telehealth. CONCLUSION: The RISE LC is a continuous, structured method for implementing strategies to improve PRO collection and use in rheumatological care, initially adapting from the Learning Collaborative model and extending to include features of a learning network. Future directions include measuring the impact of standardized PRO collection and discussion on shared decision-making and RA outcomes.

Rationale for once-daily or twice-daily dosing of zanubrutinib in patients with mantle cell lymphoma.

This report summarizes a totality-of-evidence approach supporting recommendation of a 320-mg total daily dose, either as 160-mg twice daily (BID) or 320-mg once daily (QD) for zanubrutinib in patients with mantle cell lymphoma. Data were derived from a phase 2 study in patients receiving 160-mg BID and a phase 1/2 study with similar response rates observed with 160-mg BID or 320-mg QD. Given the limited number of patients in the QD dose group, population pharmacokinetics and exposure-response analyses were employed to bridge the two regimens. The analyses showed that similar plasma exposure and BTK inhibition were achieved, and differences in trough concentration and maximum plasma concentration between the two regimens are unlikely to have a meaningful impact on efficacy and safety endpoints. The totality of data, including pharmacokinetic, pharmacodynamic, safety, efficacy, and exposure-response analyses, provided support for the recommended 320-mg total daily dose for the approved indication.

Prediction of oral hepatotoxic dose of natural products derived from traditional Chinese medicines based on SVM classifier and PBPK modeling.

The risk of drug-induced liver injury (DILI) poses a major challenge for development of natural products derived from traditional Chinese medicines (NP-TCMs). It is urgent to find a new method for the safety assessment of the NP-TCMs. Recent study has reported an in vitro/in silico method to estimate the acceptable daily intake of hepatotoxic compounds using support vector machine (SVM) classifier and physiologically based pharmacokinetic (PBPK) modeling. However, this method is not suitable for estimating the dosing schedule of compounds which are administered in multiple daily doses. Thus, in this study, the method mentioned above was in particular optimized, and used to estimate the hepatotoxic plasma concentrations of 17 NP-TCMs. Additionally, the oral dosing schedules of the triptolide, emodin, matrine and oxymatrine were also predicted by the SVM classifier and PBPK modeling. The optimization included that: (1) in vitro cytotoxicity data of 28 training set compounds was optimized using benchmark concentrations (BMC) modeling; (2) AUC of the training set compound was used as the in vivo metric instead of Cmax to better reflect the total daily exposure of compounds which are administered in multiple daily doses; (3) using the mean AUC in plasma as in vivo metric and BMC value as in vitro metric could achieve the better toxicity separation index (0.962 vs. 0.938); (4) The TSI for Cmax and BMC values was 0.985 calculated in this study, and the results indicated that BMC modeling improved the separation performance. This optimized in vitro-in vivo extrapolation (IVIVE) workflow could extrapolate in vitro BMC to blood concentrations and the oral dosing schedule which are corresponding to certain risk of hepatotoxicity. The estimated safe dosing schedule of oxymatrine by this optimized method was close to the clinical recommended dosing regimen. The results indicate that the optimized method could be used to predict the dosing schedule of compounds administered in multiple daily doses, and our optimized workflow could be helpful for the safety assessment as well as the research and development on NP-TCMs.

Soft palatal mass containing heterotopic neural tissue causing airway obstruction in a Pierre-Robin sequence patient.

Pierre-Robin sequence (PRS) patients frequently exhibit symptoms of airway obstruction due to multiple etiologies, predominantly from glossoptosis and tongue base obstruction. Rarely, these patients can have palatal mass and even rarer is one of neural origin. To date, there are few reports of heterotopic neural tissue causing airway obstruction in literature, and there are only two reports related to PRS. The objective of this report is to detail a PRS patient with obstructive airway symptoms that resolved after removal of a right-sided soft palatal mass containing heterotopic neural tissue. A 5-month-old boy with a past medical history of cleft palate, PRS status-post-mandibular distraction osteogenesis was hospitalized after continuing respiratory distress. Imaging showed a cystic submucosal mass that arose from the right soft palate. Trans-palatal and trans-oral approaches were applied for the removal. The patient tolerated the procedure well and his obstructive events have resolved at follow-up.

Does a Multidisciplinary Triage Pathway Facilitate Better Outcomes After Spine Surgery?

STUDY DESIGN: Single-center prospective non-randomized matched cohort comparison. OBJECTIVE: To compare elective lumbar spine surgery outcomes for cases triaged through a multidisciplinary spine pathway versus conventional referral processes. SUMMARY OF BACKGROUND DATA: Many health care systems have facilitated low back pain (LBP) guidelines into primary care practice by creating local or regional "pathways" with the goal of enhanced quality of care, improved patient satisfaction and optimal resource utilization, particularly for imaging and surgery. Few comparative outcomes exist for LBP pathways, particularly for surgical outcomes. METHODS: One-hundred-fifty patients (SSP group n = 75; conventional group n = 75) undergoing elective lumbar surgery for degenerative conditions between 2011 and 2016 were analyzed with 1-year follow-up. Patient self-reported outcomes included the Oswestry disability index (ODI), visual analogue pain scores (VAS) for back and leg, and EuroQol Group 5-Dimension self-report (EQ-5D). We also assessed baseline clinical features, indications for surgery, therapies received prior to surgery, type of surgery, wait times, and overall patient satisfaction. RESULTS: The groups had equivalent baseline demographics, body mass index, Saskatchewan Spine Pathway (SSP) classification of pain pattern, pain scores, functional scores, quality of life scores, indication for surgery, and type of surgery (instrumented or non-instrumented). There was no difference with respect to wait times to see the surgeon or for surgery. Wait time for magnetic resonance imaging (MRI) was significantly shorter for the SSP group (16.8 vs. 63.0 days, P < 0.001). Patients triaged through the SSP were significantly more likely to utilize multiple nonoperative treatment strategies prior to seeing the surgeon (P < 0.04). Patient satisfaction was significantly higher for SSP patients prior to surgical assessment (P = 0.03) but did not differ between groups after surgery. CONCLUSION: The SSP facilitates significantly shorter wait times for MRI and promotes nonoperative treatment strategies. Preoperative patient satisfaction is significantly higher among SSP patients, but there were no significant differences in surgical outcomes.Level of Evidence: 3.