BA

Mammalian target of rapamycin (mTOR), a serine–threonine protein kinase, operates in the phosphoinositide 3-kinase (PI3K)–protein kinase B (AKT)–mTOR signal transduction pathway regulating both normal and cancer cellular processes, including cell growth, proliferation, motility, survival, and protein and lipid synthesis.¹ Genetic alterations affecting this pathway, including mutations in receptor tyrosine kinases PI3K and AKT, occur frequently in human cancers,² supporting the rationale to develop drugs that target pathway components, such as mTOR inhibitors.

Two mTOR inhibitors are currently approved by the US Food and Drug Administration for cancer treatment: temsirolimus, for advanced renal cell carcinoma (RCC; approved 2007)³ and everolimus, for advanced RCC (approved 2009), advanced pancreatic neuroendocrine tumors (pNET; approved 2011), and hormone receptor-positive (HR-positive), human epidermal growth factor receptor-2 (HER2)-negative advanced breast cancer (approved 2012).⁴ Another mTOR inhibitor, sirolimus, is approved for use as an immunosuppressive agent and prophylactic against organ rejection after kidney transplant.⁵

Stomatitis, inflammation of the oral mucosa with contributing factors of genetic predisposition, nutritional deficiencies, infections, and immunological or hematologic dysfunction,⁶ occurs frequently as a side effect associated with mTOR inhibitor treatment.^7-9 Left untreated or managed unsatisfactorily, mTOR inhibitor-associated stomatitis (mIAS) may cause patients discomfort and trouble with maintaining adequate nutritional intake and proper oral hygiene, as well as strict adherence to cancer treatment. It is therefore important for health care providers of cancer patients receiving mTOR inhibitor treatment to be knowledgeable about this side effect. The purpose of the present systematic review of published literature is to provide a better understanding of the differential diagnosis of mIAS, the pathophysiology of mIAS, preventive strategies for patients initiating mTOR inhibitor treatment, and treatment options available to manage mIAS.

Method

The PubMed database was searched with the terms mTOR inhibitor and stomatitis (no date restriction); 79 articles were retrieved, and all abstracts were reviewed to select those relevant to the aims of this review article. To understand future directions for management and prevention of mIAS, a search of clinicaltrials.gov was performed with the terms temsirolimus everolimus stomatitis yielding 12 clinical trials, of which 4 were excluded: 1 trial was terminated due to slow accrual, the status of 1 trial had not been verified in >2 years, and 2 studies focused on efficacy outcomes. A search of the American Society of Clinical Oncology (ASCO) meeting abstracts database was performed to assess the availability of clinical trial data; the search was limited to 2011-2016 and terms were stomatitis in the title and mTOR in the abstract or title. Seven abstracts were retrieved; 2 discussed stomatitis prevention (1 as a “trial-in-progress” and 1 presented results of the trial); the other 5 abstracts presented meta-analyses or reviews of previous clinical studies to assess the risk, incidence, management, and resolution of mIAS.

Review findings

Incidence of mIAS in patients treated for cancer

Two recent meta-analyses quantified the rate of mIAS in patients receiving mTOR inhibitors. Shameem and colleagues¹⁰ identified 9 randomized studies of everolimus (8 phase 3, 1 phase 2) and 2 of temsirolimus (1 each phase 2 and 3) involving a total of 4752 patients with a variety of tumor types including angiomyolipoma, breast, gastric, giant cell astrocytoma, pNET, and RCC. Patients received everolimus monotherapy (n = 1,075) or in combination with exemestane (n = 485), tamoxifen (n = 54), letrozole (n = 137), or octreotide (n = 216). Temsirolimus was administered as monotherapy (n = 208) or in combination with interferon
(n = 210) or letrozole (n = 550). The incidence of all-grade stomatitis in the 11 studies ranged from 11%-63%, and the overall incidence of any grade stomatitis was 33.5% (95% confidence interval [CI], 21.9%-47.6%). The concurrent use of a second agent may have confounded these findings because, for example, stomatitis has been reported in pooled analyses and in postmarketing experience with letrozole.¹¹

Rugo and colleagues¹² evaluated the incidence of stomatitis in 1455 patients participating in 5 phase 3 randomized clinical trials of everolimus in breast cancer, carcinoid tumor, pNET, and RCC. Patients received everolimus monotherapy
(n = 478) or in combination with exemestane (n = 482), trastuzumab plus vinorelbine (n = 280), or octreotide
(n = 215). The incidence of stomatitis in patients receiving everolimus was 59%-71%, compared with 19%-29% in 1,071 patients of the comparator arms (placebo, and placebo–trastuzumab–vinorelbine). The overall incidence of any grade stomatitis was 67%; most events were mild (grade 1/2); 9% of stomatitis events were moderate to severe (grade 3/4).

Differential clinical presentation of mIAS and severity

Oral mucositis is a common significant adverse event (AE) that occurs in patients with cancer who receive standard chemotherapy regimens and/or radiation therapy,¹³ so it is important to recognize that the clinical presentation of mIAS differs from that of oral mucositis (Table 1, Figure ^14,15).¹⁶ mIAS shares some similarities with aphthous ulcers (also referred to as canker sores), a common oral condition with varied causes related to systemic disorders, gastrointestinal disorders, and infections, among others .¹⁷ In general, mIAS ulcers develop with a median onset of 10 days (range, 4-25 days) after initiation of mTOR inhibitor treatment and resolve in about 1-3 weeks after dose interruption/reduction of everolimus.^16,18,19 mIAS ulcers appear as distinct, oval lesions with a central gray area surrounded by peripheral erythema. They are usually localized to the movable mucosa of the mouth and oropharynx. Although mIAS lesions are usually small, they are quite painful and may cluster.

Differential diagnosis of mIAS should be made based on physical examination and medical history, with consideration given to appearance of lesions (number, size, and location), current infection status, and current medications. Specific diagnostic testing should be conducted to confirm a coexisting or alternative cause of oral lesions.¹⁷

Although there are many different scales for grading mIAS severity, the most commonly used are the National Cancer Institute Common Terminology Criteria for Adverse Events (based on patient function, symptoms, and intervention needs) and the World Health Organization oral mucositis scales (based on symptoms, clinical presentation, and interference with patient function).^20-22 These scales distinguish between mild lesions (grade 1/2) and moderate to severe lesions (grade 3/4) that cause significant pain or interfere with oral intake.

Pathophysiology of mIAS

The pathophysiology mIAS is incompletely understood. The ubiquitous role of the PI3K-AKT-mTOR pathway in regulating broad cellular functions suggests that mTOR inhibition is likely to have wide-ranging effects on many biological processes. It is not known whether disruption of one or more processes – or upsetting the balance of mTOR activities – underlies the formation of mIAS.

Differences between mIAS and oral mucositis, including clinical presentation and concomitant toxicities,^16,23 suggest that the two types of oral lesions are fundamentally distinct. This distinction is supported by animal studies in which mTOR inhibition was found to almost completely prevent the appearance of oral mucositis in irradiated mice. The protective effect of mTOR inhibition is mediated through suppression of oxidative stress generated by radiation therapy.²⁴

Although mIAS and recurrent aphthous ulcers share some similarities, it is not clear whether they also share a common pathophysiology. Recent studies suggest that patients with recurrent aphthous ulcers have immune dysfunction that leads to excessive immune response to normally innocuous substrates in the oral mucosa.²⁵ mTOR inhibition can have proinflammatory activity by promoting autophagy, a process that stimulates antigen presentation and activation of T cells that produce proinflammatory cytokines.²⁶ It is interesting to note that the incidence of stomatitis in patients receiving sirolimus after kidney transplant is relatively low, 3%-20%.⁵ Sirolimus is administered in combination with other immunosuppressants, namely cyclosporine and corticosteroids, so it suggests that concomitant use of a steroid-based regimen may have a preventive or therapeutic effect. However, posttransplant sirolimus is typically administered at relatively low doses, which might account in part for the lower incidence of mIAS observed. Ongoing clinical studies of steroid-based mouthwashes in patients receiving everolimus should shed light on this.

Other study findings have shown that inhibition of the PI3K-AKT-mTOR signaling pathway affects skin wound healing,^27,28 which raises the possibility that mIAS may stem from a diminished capacity to repair physical injuries to the oral mucosa. More research is needed to elucidate the pathophysiology of mIAS.

Preventive measures for patients initiating mTOR inhibitor treatment

There are preventive measures for mIAS that have not yet been backed up with evidence-based findings, although several clinical studies that are underway aim to address this gap (Table 2). The hypotheses about the pathophysiology of mIAS suggest that certain preventive and therapeutic interventions might be effective against mIAS. For example, two studies are evaluating the use of steroid-based mouthwashes in patients receiving everolimus, based on the hypothesis that mIAS may arise from an inflammatory process; another study will evaluate a mucoadhesive oral wound rinse, based on the hypothesis that wound protection might prevent mIAS. Glutamine suspension is also under evaluation as it is understood to have wound-preventative and tissue-repair properties, and another study is focused on dentist-guided oral management. Recent results of one of these trials (SWISH),²⁹ reported that preventative care with a dexamethasone mouthwash 3-4 times a day significantly minimized or prevented the incidence of all grades of stomatitis in women receiving everolimus plus exemestane therapy for advanced/metastatic breast cancer compared with the incidence of stomatitis observed in a previously published phase 3 trial (BOLERO-2)^30,31 of everolimus plus exemestane in the same patient population. Results from several other studies are expected soon.

Current approaches to mIAS prevention are based largely on clinical experience with chemotherapy- or radiation-induced oral mucositis (Table 3).^13,32 Preventive measures use three main strategies: establish and maintain good routine oral care; modify diet to avoid potentially damaging foods; and improve patient education about mIAS. In regard to patient education, numerous studies have reported that establishing an institutional protocol for oral care helped reduce the incidence of chemotherapy- or radiation-induced oral mucositis.^33-40 An ongoing clinical study that will randomize patients to receive oral care education from oral surgeons or instruction on brushing only (NCT02376985) is investigating whether having an oral care protocol holds for patients with mIAS. The hypothesis is that focusing attention on oral care and educating patients to recognize the onset of mIAS facilitates early detection and promotes early intervention.

Therapeutic measures for patients with mIAS

Therapeutic measures for mIAS are based largely on experience with chemotherapy- or radiation-induced oral mucositis or recurrent aphthous ulcers (Table 3) and vary in part by the severity of lesions. Treatments for mild mIAS aim to ameliorate symptoms (eg, topical analgesics for pain), protect the oral mucosa (eg, mucoadhesive gels or viscous solutions that coat the oral cavity), prevent potential sequelae (eg, prophylactic antibiotics to avoid secondary infections), and reduce inflammation/immune response (eg, steroid-based mouth rinses, topical steroids, or topical anti-inflammatory agents). Treatments for mild mIAS are generally local rather than systemic.

Treatment options for moderate to severe mIAS include systemic approaches that generally carry increased risk of AEs and, therefore, should be reserved for patients with multiple lesions, uncontrolled or poorly controlled pain, or greatly diminished oral food intake (Table 3).⁴¹ When mIAS cannot be controlled with the interventions described, the dose of the mTOR inhibitor can be reduced with the recognition that dose modification of anticancer therapy may affect disease outcomes.²⁹ The experience of reduction or interruption of treatment with everolimus in the BOLERO-2 trial as a strategy for management of AEs is discussed in a recent review.²⁹ Prescribing information for both temsirolimus and everolimus specify that grade 3 AEs be treated with temporary dose interruption, and with resolution (temsirolimus: grade ≤2; everolimus: grade ≤1), treatment may be resumed at lower doses (temsirolimus: reduce by 5 mg/week; no lower than 15 mg/week; everolimus: reduce by half the previously administered dose).^3,4 Grade 4 events due to treatment with temsirolimus may also be treated with dose interruption/reduction; the everolimus prescribing information advises treatment discontinuation for grade 4 stomatitis.

Summary and discussion

mTOR inhibitors can be effective treatments for patients with advanced cancer, specifically for advanced RCC, advanced pNET, and HR+, HER2-negative advanced breast cancer. Although mIAS may occur in many patients, it is usually grade 1 or 2 in severity. mIAS has an early onset, usually within the first 2 weeks of treatment^16,19,42 and a relatively rapid resolution, usually within 3 weeks.^16,19 Thus, most cases of mIAS are self-limiting.

The relatively recent emergence of mIAS poses short-term challenges regarding diagnosis, assessment, prevention, and treatment. Several clinical studies are underway to evaluate a range of interventions for their preventive and therapeutic efficacy in mIAS. Furthermore, our growing understanding of the underlying pathophysiology of mIAS can guide how mIAS is managed and what interventions patients receive.

Although mIAS is believed to differ from chemotherapy- or radiation-induced oral mucositis and aphthous ulcers, much can be learned from the treatment of both of these. Several strategies have been proposed to limit the occurrence of mIAS (Table 3). First, establish an oral care protocol. Educate patients who are initiating treatment with an mTOR inhibitor on implementation of the oral care protocol and emphasize adherence. Second, educate patients on the symptoms and timing of mIAS. Patients may hesitate to report mild symptoms or assume they are innocuous, so be clear that reporting all symptoms is important to allow timely clinical evaluation. Early recognition of mIAS facilitates early intervention and can prevent dose modification and interruption. Third, implement the preventive and treatment measures described. Many of the preventive measures can be incorporated into an oral care protocol.

The advent of mTOR inhibitors has clinically benefited many patients with cancer. Although side effects, like mIAS, may develop during treatment, they should not be considered insurmountable. Through education, vigilance, and aggressive management, health care providers and patients can work together to help patients maintain their quality of life while continuing to optimally address their disease.
 

Acknowledgment

The authors thank Anna Lau, PhD, and Patricia Segarini, PhD, of Percolation Communications LLC, for their editorial assistance. Funding for manuscript development was provided by Novartis Pharmaceuticals Corp.

Mammalian target of rapamycin (mTOR), a serine–threonine protein kinase, operates in the phosphoinositide 3-kinase (PI3K)–protein kinase B (AKT)–mTOR signal transduction pathway regulating both normal and cancer cellular processes, including cell growth, proliferation, motility, survival, and protein and lipid synthesis.¹ Genetic alterations affecting this pathway, including mutations in receptor tyrosine kinases PI3K and AKT, occur frequently in human cancers,² supporting the rationale to develop drugs that target pathway components, such as mTOR inhibitors.

Two mTOR inhibitors are currently approved by the US Food and Drug Administration for cancer treatment: temsirolimus, for advanced renal cell carcinoma (RCC; approved 2007)³ and everolimus, for advanced RCC (approved 2009), advanced pancreatic neuroendocrine tumors (pNET; approved 2011), and hormone receptor-positive (HR-positive), human epidermal growth factor receptor-2 (HER2)-negative advanced breast cancer (approved 2012).⁴ Another mTOR inhibitor, sirolimus, is approved for use as an immunosuppressive agent and prophylactic against organ rejection after kidney transplant.⁵

Stomatitis, inflammation of the oral mucosa with contributing factors of genetic predisposition, nutritional deficiencies, infections, and immunological or hematologic dysfunction,⁶ occurs frequently as a side effect associated with mTOR inhibitor treatment.^7-9 Left untreated or managed unsatisfactorily, mTOR inhibitor-associated stomatitis (mIAS) may cause patients discomfort and trouble with maintaining adequate nutritional intake and proper oral hygiene, as well as strict adherence to cancer treatment. It is therefore important for health care providers of cancer patients receiving mTOR inhibitor treatment to be knowledgeable about this side effect. The purpose of the present systematic review of published literature is to provide a better understanding of the differential diagnosis of mIAS, the pathophysiology of mIAS, preventive strategies for patients initiating mTOR inhibitor treatment, and treatment options available to manage mIAS.

Method

The PubMed database was searched with the terms mTOR inhibitor and stomatitis (no date restriction); 79 articles were retrieved, and all abstracts were reviewed to select those relevant to the aims of this review article. To understand future directions for management and prevention of mIAS, a search of clinicaltrials.gov was performed with the terms temsirolimus everolimus stomatitis yielding 12 clinical trials, of which 4 were excluded: 1 trial was terminated due to slow accrual, the status of 1 trial had not been verified in >2 years, and 2 studies focused on efficacy outcomes. A search of the American Society of Clinical Oncology (ASCO) meeting abstracts database was performed to assess the availability of clinical trial data; the search was limited to 2011-2016 and terms were stomatitis in the title and mTOR in the abstract or title. Seven abstracts were retrieved; 2 discussed stomatitis prevention (1 as a “trial-in-progress” and 1 presented results of the trial); the other 5 abstracts presented meta-analyses or reviews of previous clinical studies to assess the risk, incidence, management, and resolution of mIAS.

Review findings

Incidence of mIAS in patients treated for cancer

Two recent meta-analyses quantified the rate of mIAS in patients receiving mTOR inhibitors. Shameem and colleagues¹⁰ identified 9 randomized studies of everolimus (8 phase 3, 1 phase 2) and 2 of temsirolimus (1 each phase 2 and 3) involving a total of 4752 patients with a variety of tumor types including angiomyolipoma, breast, gastric, giant cell astrocytoma, pNET, and RCC. Patients received everolimus monotherapy (n = 1,075) or in combination with exemestane (n = 485), tamoxifen (n = 54), letrozole (n = 137), or octreotide (n = 216). Temsirolimus was administered as monotherapy (n = 208) or in combination with interferon
(n = 210) or letrozole (n = 550). The incidence of all-grade stomatitis in the 11 studies ranged from 11%-63%, and the overall incidence of any grade stomatitis was 33.5% (95% confidence interval [CI], 21.9%-47.6%). The concurrent use of a second agent may have confounded these findings because, for example, stomatitis has been reported in pooled analyses and in postmarketing experience with letrozole.¹¹

Rugo and colleagues¹² evaluated the incidence of stomatitis in 1455 patients participating in 5 phase 3 randomized clinical trials of everolimus in breast cancer, carcinoid tumor, pNET, and RCC. Patients received everolimus monotherapy
(n = 478) or in combination with exemestane (n = 482), trastuzumab plus vinorelbine (n = 280), or octreotide
(n = 215). The incidence of stomatitis in patients receiving everolimus was 59%-71%, compared with 19%-29% in 1,071 patients of the comparator arms (placebo, and placebo–trastuzumab–vinorelbine). The overall incidence of any grade stomatitis was 67%; most events were mild (grade 1/2); 9% of stomatitis events were moderate to severe (grade 3/4).

Differential clinical presentation of mIAS and severity

Oral mucositis is a common significant adverse event (AE) that occurs in patients with cancer who receive standard chemotherapy regimens and/or radiation therapy,¹³ so it is important to recognize that the clinical presentation of mIAS differs from that of oral mucositis (Table 1, Figure ^14,15).¹⁶ mIAS shares some similarities with aphthous ulcers (also referred to as canker sores), a common oral condition with varied causes related to systemic disorders, gastrointestinal disorders, and infections, among others .¹⁷ In general, mIAS ulcers develop with a median onset of 10 days (range, 4-25 days) after initiation of mTOR inhibitor treatment and resolve in about 1-3 weeks after dose interruption/reduction of everolimus.^16,18,19 mIAS ulcers appear as distinct, oval lesions with a central gray area surrounded by peripheral erythema. They are usually localized to the movable mucosa of the mouth and oropharynx. Although mIAS lesions are usually small, they are quite painful and may cluster.

Differential diagnosis of mIAS should be made based on physical examination and medical history, with consideration given to appearance of lesions (number, size, and location), current infection status, and current medications. Specific diagnostic testing should be conducted to confirm a coexisting or alternative cause of oral lesions.¹⁷

Although there are many different scales for grading mIAS severity, the most commonly used are the National Cancer Institute Common Terminology Criteria for Adverse Events (based on patient function, symptoms, and intervention needs) and the World Health Organization oral mucositis scales (based on symptoms, clinical presentation, and interference with patient function).^20-22 These scales distinguish between mild lesions (grade 1/2) and moderate to severe lesions (grade 3/4) that cause significant pain or interfere with oral intake.

Pathophysiology of mIAS

The pathophysiology mIAS is incompletely understood. The ubiquitous role of the PI3K-AKT-mTOR pathway in regulating broad cellular functions suggests that mTOR inhibition is likely to have wide-ranging effects on many biological processes. It is not known whether disruption of one or more processes – or upsetting the balance of mTOR activities – underlies the formation of mIAS.

Differences between mIAS and oral mucositis, including clinical presentation and concomitant toxicities,^16,23 suggest that the two types of oral lesions are fundamentally distinct. This distinction is supported by animal studies in which mTOR inhibition was found to almost completely prevent the appearance of oral mucositis in irradiated mice. The protective effect of mTOR inhibition is mediated through suppression of oxidative stress generated by radiation therapy.²⁴

Although mIAS and recurrent aphthous ulcers share some similarities, it is not clear whether they also share a common pathophysiology. Recent studies suggest that patients with recurrent aphthous ulcers have immune dysfunction that leads to excessive immune response to normally innocuous substrates in the oral mucosa.²⁵ mTOR inhibition can have proinflammatory activity by promoting autophagy, a process that stimulates antigen presentation and activation of T cells that produce proinflammatory cytokines.²⁶ It is interesting to note that the incidence of stomatitis in patients receiving sirolimus after kidney transplant is relatively low, 3%-20%.⁵ Sirolimus is administered in combination with other immunosuppressants, namely cyclosporine and corticosteroids, so it suggests that concomitant use of a steroid-based regimen may have a preventive or therapeutic effect. However, posttransplant sirolimus is typically administered at relatively low doses, which might account in part for the lower incidence of mIAS observed. Ongoing clinical studies of steroid-based mouthwashes in patients receiving everolimus should shed light on this.

Other study findings have shown that inhibition of the PI3K-AKT-mTOR signaling pathway affects skin wound healing,^27,28 which raises the possibility that mIAS may stem from a diminished capacity to repair physical injuries to the oral mucosa. More research is needed to elucidate the pathophysiology of mIAS.

Preventive measures for patients initiating mTOR inhibitor treatment

There are preventive measures for mIAS that have not yet been backed up with evidence-based findings, although several clinical studies that are underway aim to address this gap (Table 2). The hypotheses about the pathophysiology of mIAS suggest that certain preventive and therapeutic interventions might be effective against mIAS. For example, two studies are evaluating the use of steroid-based mouthwashes in patients receiving everolimus, based on the hypothesis that mIAS may arise from an inflammatory process; another study will evaluate a mucoadhesive oral wound rinse, based on the hypothesis that wound protection might prevent mIAS. Glutamine suspension is also under evaluation as it is understood to have wound-preventative and tissue-repair properties, and another study is focused on dentist-guided oral management. Recent results of one of these trials (SWISH),²⁹ reported that preventative care with a dexamethasone mouthwash 3-4 times a day significantly minimized or prevented the incidence of all grades of stomatitis in women receiving everolimus plus exemestane therapy for advanced/metastatic breast cancer compared with the incidence of stomatitis observed in a previously published phase 3 trial (BOLERO-2)^30,31 of everolimus plus exemestane in the same patient population. Results from several other studies are expected soon.

Current approaches to mIAS prevention are based largely on clinical experience with chemotherapy- or radiation-induced oral mucositis (Table 3).^13,32 Preventive measures use three main strategies: establish and maintain good routine oral care; modify diet to avoid potentially damaging foods; and improve patient education about mIAS. In regard to patient education, numerous studies have reported that establishing an institutional protocol for oral care helped reduce the incidence of chemotherapy- or radiation-induced oral mucositis.^33-40 An ongoing clinical study that will randomize patients to receive oral care education from oral surgeons or instruction on brushing only (NCT02376985) is investigating whether having an oral care protocol holds for patients with mIAS. The hypothesis is that focusing attention on oral care and educating patients to recognize the onset of mIAS facilitates early detection and promotes early intervention.

Therapeutic measures for patients with mIAS

Therapeutic measures for mIAS are based largely on experience with chemotherapy- or radiation-induced oral mucositis or recurrent aphthous ulcers (Table 3) and vary in part by the severity of lesions. Treatments for mild mIAS aim to ameliorate symptoms (eg, topical analgesics for pain), protect the oral mucosa (eg, mucoadhesive gels or viscous solutions that coat the oral cavity), prevent potential sequelae (eg, prophylactic antibiotics to avoid secondary infections), and reduce inflammation/immune response (eg, steroid-based mouth rinses, topical steroids, or topical anti-inflammatory agents). Treatments for mild mIAS are generally local rather than systemic.

Treatment options for moderate to severe mIAS include systemic approaches that generally carry increased risk of AEs and, therefore, should be reserved for patients with multiple lesions, uncontrolled or poorly controlled pain, or greatly diminished oral food intake (Table 3).⁴¹ When mIAS cannot be controlled with the interventions described, the dose of the mTOR inhibitor can be reduced with the recognition that dose modification of anticancer therapy may affect disease outcomes.²⁹ The experience of reduction or interruption of treatment with everolimus in the BOLERO-2 trial as a strategy for management of AEs is discussed in a recent review.²⁹ Prescribing information for both temsirolimus and everolimus specify that grade 3 AEs be treated with temporary dose interruption, and with resolution (temsirolimus: grade ≤2; everolimus: grade ≤1), treatment may be resumed at lower doses (temsirolimus: reduce by 5 mg/week; no lower than 15 mg/week; everolimus: reduce by half the previously administered dose).^3,4 Grade 4 events due to treatment with temsirolimus may also be treated with dose interruption/reduction; the everolimus prescribing information advises treatment discontinuation for grade 4 stomatitis.

Summary and discussion

mTOR inhibitors can be effective treatments for patients with advanced cancer, specifically for advanced RCC, advanced pNET, and HR+, HER2-negative advanced breast cancer. Although mIAS may occur in many patients, it is usually grade 1 or 2 in severity. mIAS has an early onset, usually within the first 2 weeks of treatment^16,19,42 and a relatively rapid resolution, usually within 3 weeks.^16,19 Thus, most cases of mIAS are self-limiting.

The relatively recent emergence of mIAS poses short-term challenges regarding diagnosis, assessment, prevention, and treatment. Several clinical studies are underway to evaluate a range of interventions for their preventive and therapeutic efficacy in mIAS. Furthermore, our growing understanding of the underlying pathophysiology of mIAS can guide how mIAS is managed and what interventions patients receive.

Although mIAS is believed to differ from chemotherapy- or radiation-induced oral mucositis and aphthous ulcers, much can be learned from the treatment of both of these. Several strategies have been proposed to limit the occurrence of mIAS (Table 3). First, establish an oral care protocol. Educate patients who are initiating treatment with an mTOR inhibitor on implementation of the oral care protocol and emphasize adherence. Second, educate patients on the symptoms and timing of mIAS. Patients may hesitate to report mild symptoms or assume they are innocuous, so be clear that reporting all symptoms is important to allow timely clinical evaluation. Early recognition of mIAS facilitates early intervention and can prevent dose modification and interruption. Third, implement the preventive and treatment measures described. Many of the preventive measures can be incorporated into an oral care protocol.

The advent of mTOR inhibitors has clinically benefited many patients with cancer. Although side effects, like mIAS, may develop during treatment, they should not be considered insurmountable. Through education, vigilance, and aggressive management, health care providers and patients can work together to help patients maintain their quality of life while continuing to optimally address their disease.
 

Acknowledgment

The authors thank Anna Lau, PhD, and Patricia Segarini, PhD, of Percolation Communications LLC, for their editorial assistance. Funding for manuscript development was provided by Novartis Pharmaceuticals Corp.

Mammalian target of rapamycin (mTOR), a serine–threonine protein kinase, operates in the phosphoinositide 3-kinase (PI3K)–protein kinase B (AKT)–mTOR signal transduction pathway regulating both normal and cancer cellular processes, including cell growth, proliferation, motility, survival, and protein and lipid synthesis.¹ Genetic alterations affecting this pathway, including mutations in receptor tyrosine kinases PI3K and AKT, occur frequently in human cancers,² supporting the rationale to develop drugs that target pathway components, such as mTOR inhibitors.

Two mTOR inhibitors are currently approved by the US Food and Drug Administration for cancer treatment: temsirolimus, for advanced renal cell carcinoma (RCC; approved 2007)³ and everolimus, for advanced RCC (approved 2009), advanced pancreatic neuroendocrine tumors (pNET; approved 2011), and hormone receptor-positive (HR-positive), human epidermal growth factor receptor-2 (HER2)-negative advanced breast cancer (approved 2012).⁴ Another mTOR inhibitor, sirolimus, is approved for use as an immunosuppressive agent and prophylactic against organ rejection after kidney transplant.⁵

Stomatitis, inflammation of the oral mucosa with contributing factors of genetic predisposition, nutritional deficiencies, infections, and immunological or hematologic dysfunction,⁶ occurs frequently as a side effect associated with mTOR inhibitor treatment.^7-9 Left untreated or managed unsatisfactorily, mTOR inhibitor-associated stomatitis (mIAS) may cause patients discomfort and trouble with maintaining adequate nutritional intake and proper oral hygiene, as well as strict adherence to cancer treatment. It is therefore important for health care providers of cancer patients receiving mTOR inhibitor treatment to be knowledgeable about this side effect. The purpose of the present systematic review of published literature is to provide a better understanding of the differential diagnosis of mIAS, the pathophysiology of mIAS, preventive strategies for patients initiating mTOR inhibitor treatment, and treatment options available to manage mIAS.

Method

The PubMed database was searched with the terms mTOR inhibitor and stomatitis (no date restriction); 79 articles were retrieved, and all abstracts were reviewed to select those relevant to the aims of this review article. To understand future directions for management and prevention of mIAS, a search of clinicaltrials.gov was performed with the terms temsirolimus everolimus stomatitis yielding 12 clinical trials, of which 4 were excluded: 1 trial was terminated due to slow accrual, the status of 1 trial had not been verified in >2 years, and 2 studies focused on efficacy outcomes. A search of the American Society of Clinical Oncology (ASCO) meeting abstracts database was performed to assess the availability of clinical trial data; the search was limited to 2011-2016 and terms were stomatitis in the title and mTOR in the abstract or title. Seven abstracts were retrieved; 2 discussed stomatitis prevention (1 as a “trial-in-progress” and 1 presented results of the trial); the other 5 abstracts presented meta-analyses or reviews of previous clinical studies to assess the risk, incidence, management, and resolution of mIAS.

Review findings

Incidence of mIAS in patients treated for cancer

Two recent meta-analyses quantified the rate of mIAS in patients receiving mTOR inhibitors. Shameem and colleagues¹⁰ identified 9 randomized studies of everolimus (8 phase 3, 1 phase 2) and 2 of temsirolimus (1 each phase 2 and 3) involving a total of 4752 patients with a variety of tumor types including angiomyolipoma, breast, gastric, giant cell astrocytoma, pNET, and RCC. Patients received everolimus monotherapy (n = 1,075) or in combination with exemestane (n = 485), tamoxifen (n = 54), letrozole (n = 137), or octreotide (n = 216). Temsirolimus was administered as monotherapy (n = 208) or in combination with interferon
(n = 210) or letrozole (n = 550). The incidence of all-grade stomatitis in the 11 studies ranged from 11%-63%, and the overall incidence of any grade stomatitis was 33.5% (95% confidence interval [CI], 21.9%-47.6%). The concurrent use of a second agent may have confounded these findings because, for example, stomatitis has been reported in pooled analyses and in postmarketing experience with letrozole.¹¹

Rugo and colleagues¹² evaluated the incidence of stomatitis in 1455 patients participating in 5 phase 3 randomized clinical trials of everolimus in breast cancer, carcinoid tumor, pNET, and RCC. Patients received everolimus monotherapy
(n = 478) or in combination with exemestane (n = 482), trastuzumab plus vinorelbine (n = 280), or octreotide
(n = 215). The incidence of stomatitis in patients receiving everolimus was 59%-71%, compared with 19%-29% in 1,071 patients of the comparator arms (placebo, and placebo–trastuzumab–vinorelbine). The overall incidence of any grade stomatitis was 67%; most events were mild (grade 1/2); 9% of stomatitis events were moderate to severe (grade 3/4).

Differential clinical presentation of mIAS and severity

Oral mucositis is a common significant adverse event (AE) that occurs in patients with cancer who receive standard chemotherapy regimens and/or radiation therapy,¹³ so it is important to recognize that the clinical presentation of mIAS differs from that of oral mucositis (Table 1, Figure ^14,15).¹⁶ mIAS shares some similarities with aphthous ulcers (also referred to as canker sores), a common oral condition with varied causes related to systemic disorders, gastrointestinal disorders, and infections, among others .¹⁷ In general, mIAS ulcers develop with a median onset of 10 days (range, 4-25 days) after initiation of mTOR inhibitor treatment and resolve in about 1-3 weeks after dose interruption/reduction of everolimus.^16,18,19 mIAS ulcers appear as distinct, oval lesions with a central gray area surrounded by peripheral erythema. They are usually localized to the movable mucosa of the mouth and oropharynx. Although mIAS lesions are usually small, they are quite painful and may cluster.

Differential diagnosis of mIAS should be made based on physical examination and medical history, with consideration given to appearance of lesions (number, size, and location), current infection status, and current medications. Specific diagnostic testing should be conducted to confirm a coexisting or alternative cause of oral lesions.¹⁷

Although there are many different scales for grading mIAS severity, the most commonly used are the National Cancer Institute Common Terminology Criteria for Adverse Events (based on patient function, symptoms, and intervention needs) and the World Health Organization oral mucositis scales (based on symptoms, clinical presentation, and interference with patient function).^20-22 These scales distinguish between mild lesions (grade 1/2) and moderate to severe lesions (grade 3/4) that cause significant pain or interfere with oral intake.

Pathophysiology of mIAS

The pathophysiology mIAS is incompletely understood. The ubiquitous role of the PI3K-AKT-mTOR pathway in regulating broad cellular functions suggests that mTOR inhibition is likely to have wide-ranging effects on many biological processes. It is not known whether disruption of one or more processes – or upsetting the balance of mTOR activities – underlies the formation of mIAS.

Differences between mIAS and oral mucositis, including clinical presentation and concomitant toxicities,^16,23 suggest that the two types of oral lesions are fundamentally distinct. This distinction is supported by animal studies in which mTOR inhibition was found to almost completely prevent the appearance of oral mucositis in irradiated mice. The protective effect of mTOR inhibition is mediated through suppression of oxidative stress generated by radiation therapy.²⁴

Although mIAS and recurrent aphthous ulcers share some similarities, it is not clear whether they also share a common pathophysiology. Recent studies suggest that patients with recurrent aphthous ulcers have immune dysfunction that leads to excessive immune response to normally innocuous substrates in the oral mucosa.²⁵ mTOR inhibition can have proinflammatory activity by promoting autophagy, a process that stimulates antigen presentation and activation of T cells that produce proinflammatory cytokines.²⁶ It is interesting to note that the incidence of stomatitis in patients receiving sirolimus after kidney transplant is relatively low, 3%-20%.⁵ Sirolimus is administered in combination with other immunosuppressants, namely cyclosporine and corticosteroids, so it suggests that concomitant use of a steroid-based regimen may have a preventive or therapeutic effect. However, posttransplant sirolimus is typically administered at relatively low doses, which might account in part for the lower incidence of mIAS observed. Ongoing clinical studies of steroid-based mouthwashes in patients receiving everolimus should shed light on this.

Other study findings have shown that inhibition of the PI3K-AKT-mTOR signaling pathway affects skin wound healing,^27,28 which raises the possibility that mIAS may stem from a diminished capacity to repair physical injuries to the oral mucosa. More research is needed to elucidate the pathophysiology of mIAS.

Preventive measures for patients initiating mTOR inhibitor treatment

There are preventive measures for mIAS that have not yet been backed up with evidence-based findings, although several clinical studies that are underway aim to address this gap (Table 2). The hypotheses about the pathophysiology of mIAS suggest that certain preventive and therapeutic interventions might be effective against mIAS. For example, two studies are evaluating the use of steroid-based mouthwashes in patients receiving everolimus, based on the hypothesis that mIAS may arise from an inflammatory process; another study will evaluate a mucoadhesive oral wound rinse, based on the hypothesis that wound protection might prevent mIAS. Glutamine suspension is also under evaluation as it is understood to have wound-preventative and tissue-repair properties, and another study is focused on dentist-guided oral management. Recent results of one of these trials (SWISH),²⁹ reported that preventative care with a dexamethasone mouthwash 3-4 times a day significantly minimized or prevented the incidence of all grades of stomatitis in women receiving everolimus plus exemestane therapy for advanced/metastatic breast cancer compared with the incidence of stomatitis observed in a previously published phase 3 trial (BOLERO-2)^30,31 of everolimus plus exemestane in the same patient population. Results from several other studies are expected soon.

Current approaches to mIAS prevention are based largely on clinical experience with chemotherapy- or radiation-induced oral mucositis (Table 3).^13,32 Preventive measures use three main strategies: establish and maintain good routine oral care; modify diet to avoid potentially damaging foods; and improve patient education about mIAS. In regard to patient education, numerous studies have reported that establishing an institutional protocol for oral care helped reduce the incidence of chemotherapy- or radiation-induced oral mucositis.^33-40 An ongoing clinical study that will randomize patients to receive oral care education from oral surgeons or instruction on brushing only (NCT02376985) is investigating whether having an oral care protocol holds for patients with mIAS. The hypothesis is that focusing attention on oral care and educating patients to recognize the onset of mIAS facilitates early detection and promotes early intervention.

Therapeutic measures for patients with mIAS

Therapeutic measures for mIAS are based largely on experience with chemotherapy- or radiation-induced oral mucositis or recurrent aphthous ulcers (Table 3) and vary in part by the severity of lesions. Treatments for mild mIAS aim to ameliorate symptoms (eg, topical analgesics for pain), protect the oral mucosa (eg, mucoadhesive gels or viscous solutions that coat the oral cavity), prevent potential sequelae (eg, prophylactic antibiotics to avoid secondary infections), and reduce inflammation/immune response (eg, steroid-based mouth rinses, topical steroids, or topical anti-inflammatory agents). Treatments for mild mIAS are generally local rather than systemic.

Treatment options for moderate to severe mIAS include systemic approaches that generally carry increased risk of AEs and, therefore, should be reserved for patients with multiple lesions, uncontrolled or poorly controlled pain, or greatly diminished oral food intake (Table 3).⁴¹ When mIAS cannot be controlled with the interventions described, the dose of the mTOR inhibitor can be reduced with the recognition that dose modification of anticancer therapy may affect disease outcomes.²⁹ The experience of reduction or interruption of treatment with everolimus in the BOLERO-2 trial as a strategy for management of AEs is discussed in a recent review.²⁹ Prescribing information for both temsirolimus and everolimus specify that grade 3 AEs be treated with temporary dose interruption, and with resolution (temsirolimus: grade ≤2; everolimus: grade ≤1), treatment may be resumed at lower doses (temsirolimus: reduce by 5 mg/week; no lower than 15 mg/week; everolimus: reduce by half the previously administered dose).^3,4 Grade 4 events due to treatment with temsirolimus may also be treated with dose interruption/reduction; the everolimus prescribing information advises treatment discontinuation for grade 4 stomatitis.

Summary and discussion

mTOR inhibitors can be effective treatments for patients with advanced cancer, specifically for advanced RCC, advanced pNET, and HR+, HER2-negative advanced breast cancer. Although mIAS may occur in many patients, it is usually grade 1 or 2 in severity. mIAS has an early onset, usually within the first 2 weeks of treatment^16,19,42 and a relatively rapid resolution, usually within 3 weeks.^16,19 Thus, most cases of mIAS are self-limiting.

The relatively recent emergence of mIAS poses short-term challenges regarding diagnosis, assessment, prevention, and treatment. Several clinical studies are underway to evaluate a range of interventions for their preventive and therapeutic efficacy in mIAS. Furthermore, our growing understanding of the underlying pathophysiology of mIAS can guide how mIAS is managed and what interventions patients receive.

Although mIAS is believed to differ from chemotherapy- or radiation-induced oral mucositis and aphthous ulcers, much can be learned from the treatment of both of these. Several strategies have been proposed to limit the occurrence of mIAS (Table 3). First, establish an oral care protocol. Educate patients who are initiating treatment with an mTOR inhibitor on implementation of the oral care protocol and emphasize adherence. Second, educate patients on the symptoms and timing of mIAS. Patients may hesitate to report mild symptoms or assume they are innocuous, so be clear that reporting all symptoms is important to allow timely clinical evaluation. Early recognition of mIAS facilitates early intervention and can prevent dose modification and interruption. Third, implement the preventive and treatment measures described. Many of the preventive measures can be incorporated into an oral care protocol.

The advent of mTOR inhibitors has clinically benefited many patients with cancer. Although side effects, like mIAS, may develop during treatment, they should not be considered insurmountable. Through education, vigilance, and aggressive management, health care providers and patients can work together to help patients maintain their quality of life while continuing to optimally address their disease.
 

Acknowledgment

The authors thank Anna Lau, PhD, and Patricia Segarini, PhD, of Percolation Communications LLC, for their editorial assistance. Funding for manuscript development was provided by Novartis Pharmaceuticals Corp.

From the Case Western Reserve University School of Medicine, Cleveland, OH.

Abstract

• Objective: To improve operating room (OR) scheduling efficiency at a large academic institution through the use of an academic-practice partnership and quality improvement (QI) methods.
• Methods: The OR administrative team at a large academic hospital partnered with students in a graduate level QI course to apply QI tools to the problem of OR efficiency.
• Results: The team found wide variation in the way that surgeries were scheduled and other factors that contributed to inefficient OR utilization. A plan-do-study-act (PDSA) cycle was applied to the problem of discrepancy in surgeons’ interpretation of case length, resulting in poor case length accuracy. Our intervention, adding time on the schedule for cases, did not show consistent improvement in case length accuracy.
• Conclusion: Although our intervention did not lead to sustained improvements in OR scheduling efficiency, our project demonstrates how QI tools can be taught and applied in an academic course to address a management problem. Further research is needed to study the impact of student teams on health care improvement.

Operating rooms are one of the most costly departments of a hospital. At University Hospitals Case Medical Center (UHCMC), as at many hospitals, operating room utilization is a key area of focus for both operating room (OR) and hospital administrators. Efficient use of the OR is an important aspect of a hospital’s finances and patient-centeredness.

UHCMC uses block scheduling, a common OR scheduling design. Each surgical department is allotted a certain number of blocks (hours of reserved OR time) that they are responsible for filling with surgical cases and that the hospital is responsible for staffing. Block utilization rate is a metric commonly used to measure OR efficiency. It divides the time that the OR is in use by the total block time allocated to the department (while accounting for room turnaround time). An industry benchmark is 75% block utilization [1], which was adopted as an internal target at UHCMC. Achieving this metric is necessary because the hospital (rather than each individual surgical department) is responsible for ensuring that the appropriate amount of non-surgeon staff (eg, anesthesiologists, nurses, scrub techs, and facilities staff) is available. Poor utilization rates indicate that the staff and equipment are inefficiently used, which can impact the hospital’s financial well-being [2]. Block utilization is the result of a complex system, making it challenging to improve. Many people are involved in scheduling, and a large degree of inherent uncertainty exists in the system.

At UHCMC, block utilization rates by department ranged from 52% to 80%, with an overall utilization of 64% from February to July 2014. Given this wide variation, higher level management staff in the OR initiated a project in which OR administrators partnered with students in a graduate level QI course in an effort to improve overall block utilization. They believed that improving block utilization rate would improve the effectiveness, patient-centeredness, and efficiency of care, health care delivery goals described by the Institute of Medicine [3].

Methods

Setting

The OR at UHCMC contains 4 operating suites that serve over 25,000 patients per year and train over 900 residents each year. Nearly 250 surgeons in 23 departments use the OR. The OR schedule at our institution is coordinated by block scheduling, as described above. If a surgical department cannot fill the block, they must release the time to central scheduling for re-allocation of the time to another department.

Application of QI Process

This QI project was an academic-practice collaboration between UHCMC and a graduate level course at Case Western Reserve University called The Continual Improvement of Healthcare: an Interdisciplinary Course [4]. Faculty course instructors solicit applications of QI projects from departments at UHCMC. The project team consisted of 4 students (from medicine, social work, public health, and bioethics), 2 administrative staff from UHCMC, and a QI coach who is on the faculty at Case Western. Guidance was provided by 2 faculty facilitators. The students attended 15 weekly class sessions, 4 meetings with the project team, numerous data gathering sessions with other hospital staff, and held a handful of outside-class student team meetings. An early class session was devoted to team skills and the Seven-Step meeting process  [5]. Each classroom session consisted of structured group activities to practice the tools of the QI process. 

Tool 1: Global Aim

The team first established a global aim: to improve the OR block utilization rate at UHCMC. This aim was based on the initial project proposal from UHCMC. The global aim explains the reason that the project team was established, and frames all future work [7].

Tool 2: Industry Assessment

Based on the global aim, the student team performed an industry assessment in order to understand strategies for improving block utilization rate in use at other institutions. Peer-reviewed journal articles and case reports were reviewed and the student team was able to contact a team at another institution working on similar issues.

Overall, 2 broad categories of interventions to improve block utilization were identified. Some institutions addressed the way time in the OR was scheduled. They made improvements to how block time was allotted, timing of cases, and dealing with add-on cases [8]. Others focused on using time in the OR more efficiently by addressing room turnover, delays including waiting for surgeons, and waiting for hospital beds [9]. Because the specific case mix of each hospital is so distinct, hospitals that successfully made changes all used a variety of interventions [10–12]. After the industry assessment, the student team realized that there would be a large number of possible approaches to the problem of block utilization, and a better understanding of the actual process of scheduling at UHCMC was necessary to find an area of focus.

Tool 3: Process Map

As the project team began to address the global aim of improving OR block utilization at UHCMC, they needed to have a thorough understanding of how OR time was allotted and used. To do this, the student team created a process map by interviewing process stakeholders, including the OR managers and department schedulers in orthopedics, general surgery, and urology, as suggested by the OR managers. The perspective of these staff were critical to understanding the process of operating room scheduling.

Through the creation of the process map, the project team found that there was wide variation in the process and structure for scheduling surgeries. Some departments used one central scheduler while others used individual secretaries for each surgeon. Some surgeons maintained control over changing their schedule, while others did not. Further, the project team learned that the metric of block utilization rate was of varying importance to people working on the ground.

Tool 4: Fishbone Diagram

After understanding the process, the project team considered all of the factors that 

Tool 5: Specific Aim

Though the global aim was to improve block utilization, the project team needed to chose a specific aim that met S.M.A.R.T criteria: Specific, Measureable, Achievable, Results-focused, and Time-bound [7]. After considering multiple potential areas of initial focus, the OR staff suggested focusing on the issue of case length accuracy. In qualitative interviews, the student team had found that the surgery request forms ask for “case length,” and the schedulers were not sure how the surgeons defined it. When the OR is booked for an operation, the amount of time blocked out is the time from when the patient is brought into the operating room to the time that the patient leaves the room, or WIWO (Wheels In Wheels Out). This WIWO time includes anesthesia induction and preparations for surgery such as positioning. Some surgeons think about case length as only the time that the patient is operated on, or CTC (Cut to Close). Thus, the surgeon may be requesting less time than is really necessary for the case if he or she is only thinking about CTC time. The student team created a survey and found that 2 urology surgeons considered case length to be WIWO, and 4 considered case length to mean CTC.

Tools 6 and 7: PDSA Cycle and Control Charts

The Plan-Do-Study-Act cycle is an iterative plan of action for designing and testing a specific change [7]. This part of the QI cycle involved implementing and testing a change to address our specific aim. As the first cycle of change, the team requested that the scheduler add 15 minutes to the surgeons’ requested case time over 1 week. Of the urologists scheduled that week, one had used CTC and the other had not completed the student team’s survey. In order to study the change, the project team used control charts for the 2 surgeons whose case times were adapted. Prior to the intervention, the surgeons averaged at least 20 minutes over their scheduled time, with wide variation. Surgeons were infrequently completing cases at or below their requested case time. Most of the inaccuracy came from going long. The team used control charts to understand the impact of the change. The control charts showed that after the change in scheduling time, the 2 surgeons still went over their allotted case time, but to a lesser degree.

After gaining new information, the next step in the PDSA cycle is to determine the next test of change. The student team recommended sharing these data with the surgeons to consider next steps in improving block utilization, though time constraints of the semester limited continued involvement of the student team in the next PDSA cycle.

Discussion

Through the application of QI tools, new insight was gained about OR efficiency and potential improvements. The student team talked to numerous staff involved in scheduling and each discussion increased understanding of the issues that lead to OR inefficiency. The process map and fishbone diagram provided a visual expression of how small issues could impact the overall OR system. Application of QI tools also led the team to the discovery that surgeons may be interpreting case length in disparate ways, contributing to problems with scheduling.

Though the intervention did not have significant impact over 1 week, more time for subsequent PDSA cycles may have resulted in clinical improvements. Despite the limitations, the student team uncovered an important aspect of the block scheduling process, providing valuable information and insight for the department around this scheduling issue. The student team’s work was shared between multiple surgical departments, and the QI work in the department is ongoing.

Implications for Health Care Institutions

Nontraditional Projects Can Work

The issue of OR utilization is perhaps not a “traditional” QI project given the macro nature of the problem. Once it was broken down into discrete processes, problems such as OR turnover, scheduling redundancies, and others look much more like traditional QI projects. It may be beneficial to institutions to broaden the scope of QI to problems that may, at first glance, seem out of the realm of process mapping, fishbone diagramming, and SMART aims. QI tools can turn management problems into projects that can be tackled by small teams, creating an culture of change in an organization [13].

Benefits of Student Teams

There are clear benefits to the institution working with students. Our hospital-based team members found it beneficial to have independent observers review the process and recommend improvements. Students were able to challenge the status quo and point out inefficiencies that have remained due to institutional complacency and lack of resources. The hospital employees were impressed and surprised that the students found the misunderstanding about case length, and noted that it suggests that there may be other places where there are miscommunications between various people involved in OR scheduling. The students’ energy and time was supported by the QI expertise of the course instructors, and the practical knowledge of the hospital-based team members. Similar benefits have been noted by others utilizing collaborative QI educational models [14,15].

Benefits for Students

For the students on the team, the opportunity to apply QI concepts to the real world was a unique learning opportunity. First, the project was truly interdisciplinary. The students were from varied fields and they worked with schedulers, surgeons, and office managers providing the students with insight into the meaning and perspectives of interprofessional collaboration. The students appreciated the complexity and tensions of the OR staff who were working to balance the schedules of nurses, anesthesiologists, and other OR support staff. Additionally, interdisciplinary collaboration in health care is of increasing importance in everyday practice [16,17]. A strong understanding of collaboration across professions will be a cornerstone of the students’ credentials as they move into the workforce.

There is also value in adding real work experience to academics. The students were able to appreciate not only the concepts of QI but the actual challenges of implementing QI methodology in an institution where people had varying levels of buy-in. Quality improvement is about more than sitting at a whiteboard coming up with charts—it is about enacting actual change and understanding specific real-world situations. The hospital collaboration allowed the students to gain experience that is impossible to replicate in the classroom.

Limitations and Barriers

As noted in other academic-practice collaborations, the limitation of completing the project in one semester presents a barrier to collaboration; the working world does not operate on an academic timeline [14]. Students were limited to only testing one cycle of change. This part of the semester was disappointing as the students would have liked to implement multiple PDSA cycles. The OR managers faced barriers as well; they invested time in educating students who would soon move on, and would have to repeat the process with a new group of students. The department has continued on with this work, but losing the students who they oriented was not ideal.

The course instructors were flexible in allowing the project team to spend the majority of time breaking down the problem of OR block utilization into testable changes, which was the bulk of our work. However, the skill that the team was able to dedicate the least amount time to, testing and implementing change, is useful for the students to learn and beneficial for the organization. Moving forward, allowing teams to build on the previous semester’s work, and even implementing a student handoff, might be tried.

Future Directions

Although our intervention did not lead to sustained improvements in OR scheduling efficiency, our project demonstrates how QI tools can be taught and applied in an academic course to address a management problem. Research to specifically understand institutional benefits of academic-practice collaborations would be helpful in recruiting partners and furthering best practices for participants in these partnerships. Research is also needed to understand the impact of QI collaborative models such as the one described in this paper on improving interprofessional teamwork and communication skills, as called for by health care professional educators [16].

Corresponding author: Danielle O’Rourke-Suchoff, BA, Case Western Reserve University School of Medicine, Office of Student Affairs, 10900 Euclid Ave., Cleveland, OH 44106, dko@case.edu.

Financial disclosures: none.

From the Case Western Reserve University School of Medicine, Cleveland, OH.

Abstract

• Objective: To improve operating room (OR) scheduling efficiency at a large academic institution through the use of an academic-practice partnership and quality improvement (QI) methods.
• Methods: The OR administrative team at a large academic hospital partnered with students in a graduate level QI course to apply QI tools to the problem of OR efficiency.
• Results: The team found wide variation in the way that surgeries were scheduled and other factors that contributed to inefficient OR utilization. A plan-do-study-act (PDSA) cycle was applied to the problem of discrepancy in surgeons’ interpretation of case length, resulting in poor case length accuracy. Our intervention, adding time on the schedule for cases, did not show consistent improvement in case length accuracy.
• Conclusion: Although our intervention did not lead to sustained improvements in OR scheduling efficiency, our project demonstrates how QI tools can be taught and applied in an academic course to address a management problem. Further research is needed to study the impact of student teams on health care improvement.

Operating rooms are one of the most costly departments of a hospital. At University Hospitals Case Medical Center (UHCMC), as at many hospitals, operating room utilization is a key area of focus for both operating room (OR) and hospital administrators. Efficient use of the OR is an important aspect of a hospital’s finances and patient-centeredness.

UHCMC uses block scheduling, a common OR scheduling design. Each surgical department is allotted a certain number of blocks (hours of reserved OR time) that they are responsible for filling with surgical cases and that the hospital is responsible for staffing. Block utilization rate is a metric commonly used to measure OR efficiency. It divides the time that the OR is in use by the total block time allocated to the department (while accounting for room turnaround time). An industry benchmark is 75% block utilization [1], which was adopted as an internal target at UHCMC. Achieving this metric is necessary because the hospital (rather than each individual surgical department) is responsible for ensuring that the appropriate amount of non-surgeon staff (eg, anesthesiologists, nurses, scrub techs, and facilities staff) is available. Poor utilization rates indicate that the staff and equipment are inefficiently used, which can impact the hospital’s financial well-being [2]. Block utilization is the result of a complex system, making it challenging to improve. Many people are involved in scheduling, and a large degree of inherent uncertainty exists in the system.

At UHCMC, block utilization rates by department ranged from 52% to 80%, with an overall utilization of 64% from February to July 2014. Given this wide variation, higher level management staff in the OR initiated a project in which OR administrators partnered with students in a graduate level QI course in an effort to improve overall block utilization. They believed that improving block utilization rate would improve the effectiveness, patient-centeredness, and efficiency of care, health care delivery goals described by the Institute of Medicine [3].

Methods

Setting

The OR at UHCMC contains 4 operating suites that serve over 25,000 patients per year and train over 900 residents each year. Nearly 250 surgeons in 23 departments use the OR. The OR schedule at our institution is coordinated by block scheduling, as described above. If a surgical department cannot fill the block, they must release the time to central scheduling for re-allocation of the time to another department.

Application of QI Process

This QI project was an academic-practice collaboration between UHCMC and a graduate level course at Case Western Reserve University called The Continual Improvement of Healthcare: an Interdisciplinary Course [4]. Faculty course instructors solicit applications of QI projects from departments at UHCMC. The project team consisted of 4 students (from medicine, social work, public health, and bioethics), 2 administrative staff from UHCMC, and a QI coach who is on the faculty at Case Western. Guidance was provided by 2 faculty facilitators. The students attended 15 weekly class sessions, 4 meetings with the project team, numerous data gathering sessions with other hospital staff, and held a handful of outside-class student team meetings. An early class session was devoted to team skills and the Seven-Step meeting process  [5]. Each classroom session consisted of structured group activities to practice the tools of the QI process. 

Tool 1: Global Aim

The team first established a global aim: to improve the OR block utilization rate at UHCMC. This aim was based on the initial project proposal from UHCMC. The global aim explains the reason that the project team was established, and frames all future work [7].

Tool 2: Industry Assessment

Based on the global aim, the student team performed an industry assessment in order to understand strategies for improving block utilization rate in use at other institutions. Peer-reviewed journal articles and case reports were reviewed and the student team was able to contact a team at another institution working on similar issues.

Overall, 2 broad categories of interventions to improve block utilization were identified. Some institutions addressed the way time in the OR was scheduled. They made improvements to how block time was allotted, timing of cases, and dealing with add-on cases [8]. Others focused on using time in the OR more efficiently by addressing room turnover, delays including waiting for surgeons, and waiting for hospital beds [9]. Because the specific case mix of each hospital is so distinct, hospitals that successfully made changes all used a variety of interventions [10–12]. After the industry assessment, the student team realized that there would be a large number of possible approaches to the problem of block utilization, and a better understanding of the actual process of scheduling at UHCMC was necessary to find an area of focus.

Tool 3: Process Map

As the project team began to address the global aim of improving OR block utilization at UHCMC, they needed to have a thorough understanding of how OR time was allotted and used. To do this, the student team created a process map by interviewing process stakeholders, including the OR managers and department schedulers in orthopedics, general surgery, and urology, as suggested by the OR managers. The perspective of these staff were critical to understanding the process of operating room scheduling.

Through the creation of the process map, the project team found that there was wide variation in the process and structure for scheduling surgeries. Some departments used one central scheduler while others used individual secretaries for each surgeon. Some surgeons maintained control over changing their schedule, while others did not. Further, the project team learned that the metric of block utilization rate was of varying importance to people working on the ground.

Tool 4: Fishbone Diagram

After understanding the process, the project team considered all of the factors that 

Tool 5: Specific Aim

Though the global aim was to improve block utilization, the project team needed to chose a specific aim that met S.M.A.R.T criteria: Specific, Measureable, Achievable, Results-focused, and Time-bound [7]. After considering multiple potential areas of initial focus, the OR staff suggested focusing on the issue of case length accuracy. In qualitative interviews, the student team had found that the surgery request forms ask for “case length,” and the schedulers were not sure how the surgeons defined it. When the OR is booked for an operation, the amount of time blocked out is the time from when the patient is brought into the operating room to the time that the patient leaves the room, or WIWO (Wheels In Wheels Out). This WIWO time includes anesthesia induction and preparations for surgery such as positioning. Some surgeons think about case length as only the time that the patient is operated on, or CTC (Cut to Close). Thus, the surgeon may be requesting less time than is really necessary for the case if he or she is only thinking about CTC time. The student team created a survey and found that 2 urology surgeons considered case length to be WIWO, and 4 considered case length to mean CTC.

Tools 6 and 7: PDSA Cycle and Control Charts

The Plan-Do-Study-Act cycle is an iterative plan of action for designing and testing a specific change [7]. This part of the QI cycle involved implementing and testing a change to address our specific aim. As the first cycle of change, the team requested that the scheduler add 15 minutes to the surgeons’ requested case time over 1 week. Of the urologists scheduled that week, one had used CTC and the other had not completed the student team’s survey. In order to study the change, the project team used control charts for the 2 surgeons whose case times were adapted. Prior to the intervention, the surgeons averaged at least 20 minutes over their scheduled time, with wide variation. Surgeons were infrequently completing cases at or below their requested case time. Most of the inaccuracy came from going long. The team used control charts to understand the impact of the change. The control charts showed that after the change in scheduling time, the 2 surgeons still went over their allotted case time, but to a lesser degree.

After gaining new information, the next step in the PDSA cycle is to determine the next test of change. The student team recommended sharing these data with the surgeons to consider next steps in improving block utilization, though time constraints of the semester limited continued involvement of the student team in the next PDSA cycle.

Discussion

Through the application of QI tools, new insight was gained about OR efficiency and potential improvements. The student team talked to numerous staff involved in scheduling and each discussion increased understanding of the issues that lead to OR inefficiency. The process map and fishbone diagram provided a visual expression of how small issues could impact the overall OR system. Application of QI tools also led the team to the discovery that surgeons may be interpreting case length in disparate ways, contributing to problems with scheduling.

Though the intervention did not have significant impact over 1 week, more time for subsequent PDSA cycles may have resulted in clinical improvements. Despite the limitations, the student team uncovered an important aspect of the block scheduling process, providing valuable information and insight for the department around this scheduling issue. The student team’s work was shared between multiple surgical departments, and the QI work in the department is ongoing.

Implications for Health Care Institutions

Nontraditional Projects Can Work

The issue of OR utilization is perhaps not a “traditional” QI project given the macro nature of the problem. Once it was broken down into discrete processes, problems such as OR turnover, scheduling redundancies, and others look much more like traditional QI projects. It may be beneficial to institutions to broaden the scope of QI to problems that may, at first glance, seem out of the realm of process mapping, fishbone diagramming, and SMART aims. QI tools can turn management problems into projects that can be tackled by small teams, creating an culture of change in an organization [13].

Benefits of Student Teams

There are clear benefits to the institution working with students. Our hospital-based team members found it beneficial to have independent observers review the process and recommend improvements. Students were able to challenge the status quo and point out inefficiencies that have remained due to institutional complacency and lack of resources. The hospital employees were impressed and surprised that the students found the misunderstanding about case length, and noted that it suggests that there may be other places where there are miscommunications between various people involved in OR scheduling. The students’ energy and time was supported by the QI expertise of the course instructors, and the practical knowledge of the hospital-based team members. Similar benefits have been noted by others utilizing collaborative QI educational models [14,15].

Benefits for Students

For the students on the team, the opportunity to apply QI concepts to the real world was a unique learning opportunity. First, the project was truly interdisciplinary. The students were from varied fields and they worked with schedulers, surgeons, and office managers providing the students with insight into the meaning and perspectives of interprofessional collaboration. The students appreciated the complexity and tensions of the OR staff who were working to balance the schedules of nurses, anesthesiologists, and other OR support staff. Additionally, interdisciplinary collaboration in health care is of increasing importance in everyday practice [16,17]. A strong understanding of collaboration across professions will be a cornerstone of the students’ credentials as they move into the workforce.

There is also value in adding real work experience to academics. The students were able to appreciate not only the concepts of QI but the actual challenges of implementing QI methodology in an institution where people had varying levels of buy-in. Quality improvement is about more than sitting at a whiteboard coming up with charts—it is about enacting actual change and understanding specific real-world situations. The hospital collaboration allowed the students to gain experience that is impossible to replicate in the classroom.

Limitations and Barriers

As noted in other academic-practice collaborations, the limitation of completing the project in one semester presents a barrier to collaboration; the working world does not operate on an academic timeline [14]. Students were limited to only testing one cycle of change. This part of the semester was disappointing as the students would have liked to implement multiple PDSA cycles. The OR managers faced barriers as well; they invested time in educating students who would soon move on, and would have to repeat the process with a new group of students. The department has continued on with this work, but losing the students who they oriented was not ideal.

The course instructors were flexible in allowing the project team to spend the majority of time breaking down the problem of OR block utilization into testable changes, which was the bulk of our work. However, the skill that the team was able to dedicate the least amount time to, testing and implementing change, is useful for the students to learn and beneficial for the organization. Moving forward, allowing teams to build on the previous semester’s work, and even implementing a student handoff, might be tried.

Future Directions

Although our intervention did not lead to sustained improvements in OR scheduling efficiency, our project demonstrates how QI tools can be taught and applied in an academic course to address a management problem. Research to specifically understand institutional benefits of academic-practice collaborations would be helpful in recruiting partners and furthering best practices for participants in these partnerships. Research is also needed to understand the impact of QI collaborative models such as the one described in this paper on improving interprofessional teamwork and communication skills, as called for by health care professional educators [16].

Corresponding author: Danielle O’Rourke-Suchoff, BA, Case Western Reserve University School of Medicine, Office of Student Affairs, 10900 Euclid Ave., Cleveland, OH 44106, dko@case.edu.

Financial disclosures: none.

From the Case Western Reserve University School of Medicine, Cleveland, OH.

Abstract

• Objective: To improve operating room (OR) scheduling efficiency at a large academic institution through the use of an academic-practice partnership and quality improvement (QI) methods.
• Methods: The OR administrative team at a large academic hospital partnered with students in a graduate level QI course to apply QI tools to the problem of OR efficiency.
• Results: The team found wide variation in the way that surgeries were scheduled and other factors that contributed to inefficient OR utilization. A plan-do-study-act (PDSA) cycle was applied to the problem of discrepancy in surgeons’ interpretation of case length, resulting in poor case length accuracy. Our intervention, adding time on the schedule for cases, did not show consistent improvement in case length accuracy.
• Conclusion: Although our intervention did not lead to sustained improvements in OR scheduling efficiency, our project demonstrates how QI tools can be taught and applied in an academic course to address a management problem. Further research is needed to study the impact of student teams on health care improvement.

Operating rooms are one of the most costly departments of a hospital. At University Hospitals Case Medical Center (UHCMC), as at many hospitals, operating room utilization is a key area of focus for both operating room (OR) and hospital administrators. Efficient use of the OR is an important aspect of a hospital’s finances and patient-centeredness.

UHCMC uses block scheduling, a common OR scheduling design. Each surgical department is allotted a certain number of blocks (hours of reserved OR time) that they are responsible for filling with surgical cases and that the hospital is responsible for staffing. Block utilization rate is a metric commonly used to measure OR efficiency. It divides the time that the OR is in use by the total block time allocated to the department (while accounting for room turnaround time). An industry benchmark is 75% block utilization [1], which was adopted as an internal target at UHCMC. Achieving this metric is necessary because the hospital (rather than each individual surgical department) is responsible for ensuring that the appropriate amount of non-surgeon staff (eg, anesthesiologists, nurses, scrub techs, and facilities staff) is available. Poor utilization rates indicate that the staff and equipment are inefficiently used, which can impact the hospital’s financial well-being [2]. Block utilization is the result of a complex system, making it challenging to improve. Many people are involved in scheduling, and a large degree of inherent uncertainty exists in the system.

At UHCMC, block utilization rates by department ranged from 52% to 80%, with an overall utilization of 64% from February to July 2014. Given this wide variation, higher level management staff in the OR initiated a project in which OR administrators partnered with students in a graduate level QI course in an effort to improve overall block utilization. They believed that improving block utilization rate would improve the effectiveness, patient-centeredness, and efficiency of care, health care delivery goals described by the Institute of Medicine [3].

Methods

Setting

The OR at UHCMC contains 4 operating suites that serve over 25,000 patients per year and train over 900 residents each year. Nearly 250 surgeons in 23 departments use the OR. The OR schedule at our institution is coordinated by block scheduling, as described above. If a surgical department cannot fill the block, they must release the time to central scheduling for re-allocation of the time to another department.

Application of QI Process

This QI project was an academic-practice collaboration between UHCMC and a graduate level course at Case Western Reserve University called The Continual Improvement of Healthcare: an Interdisciplinary Course [4]. Faculty course instructors solicit applications of QI projects from departments at UHCMC. The project team consisted of 4 students (from medicine, social work, public health, and bioethics), 2 administrative staff from UHCMC, and a QI coach who is on the faculty at Case Western. Guidance was provided by 2 faculty facilitators. The students attended 15 weekly class sessions, 4 meetings with the project team, numerous data gathering sessions with other hospital staff, and held a handful of outside-class student team meetings. An early class session was devoted to team skills and the Seven-Step meeting process  [5]. Each classroom session consisted of structured group activities to practice the tools of the QI process. 

Tool 1: Global Aim

The team first established a global aim: to improve the OR block utilization rate at UHCMC. This aim was based on the initial project proposal from UHCMC. The global aim explains the reason that the project team was established, and frames all future work [7].

Tool 2: Industry Assessment

Based on the global aim, the student team performed an industry assessment in order to understand strategies for improving block utilization rate in use at other institutions. Peer-reviewed journal articles and case reports were reviewed and the student team was able to contact a team at another institution working on similar issues.

Overall, 2 broad categories of interventions to improve block utilization were identified. Some institutions addressed the way time in the OR was scheduled. They made improvements to how block time was allotted, timing of cases, and dealing with add-on cases [8]. Others focused on using time in the OR more efficiently by addressing room turnover, delays including waiting for surgeons, and waiting for hospital beds [9]. Because the specific case mix of each hospital is so distinct, hospitals that successfully made changes all used a variety of interventions [10–12]. After the industry assessment, the student team realized that there would be a large number of possible approaches to the problem of block utilization, and a better understanding of the actual process of scheduling at UHCMC was necessary to find an area of focus.

Tool 3: Process Map

As the project team began to address the global aim of improving OR block utilization at UHCMC, they needed to have a thorough understanding of how OR time was allotted and used. To do this, the student team created a process map by interviewing process stakeholders, including the OR managers and department schedulers in orthopedics, general surgery, and urology, as suggested by the OR managers. The perspective of these staff were critical to understanding the process of operating room scheduling.

Through the creation of the process map, the project team found that there was wide variation in the process and structure for scheduling surgeries. Some departments used one central scheduler while others used individual secretaries for each surgeon. Some surgeons maintained control over changing their schedule, while others did not. Further, the project team learned that the metric of block utilization rate was of varying importance to people working on the ground.

Tool 4: Fishbone Diagram

After understanding the process, the project team considered all of the factors that 

Tool 5: Specific Aim

Though the global aim was to improve block utilization, the project team needed to chose a specific aim that met S.M.A.R.T criteria: Specific, Measureable, Achievable, Results-focused, and Time-bound [7]. After considering multiple potential areas of initial focus, the OR staff suggested focusing on the issue of case length accuracy. In qualitative interviews, the student team had found that the surgery request forms ask for “case length,” and the schedulers were not sure how the surgeons defined it. When the OR is booked for an operation, the amount of time blocked out is the time from when the patient is brought into the operating room to the time that the patient leaves the room, or WIWO (Wheels In Wheels Out). This WIWO time includes anesthesia induction and preparations for surgery such as positioning. Some surgeons think about case length as only the time that the patient is operated on, or CTC (Cut to Close). Thus, the surgeon may be requesting less time than is really necessary for the case if he or she is only thinking about CTC time. The student team created a survey and found that 2 urology surgeons considered case length to be WIWO, and 4 considered case length to mean CTC.

Tools 6 and 7: PDSA Cycle and Control Charts

The Plan-Do-Study-Act cycle is an iterative plan of action for designing and testing a specific change [7]. This part of the QI cycle involved implementing and testing a change to address our specific aim. As the first cycle of change, the team requested that the scheduler add 15 minutes to the surgeons’ requested case time over 1 week. Of the urologists scheduled that week, one had used CTC and the other had not completed the student team’s survey. In order to study the change, the project team used control charts for the 2 surgeons whose case times were adapted. Prior to the intervention, the surgeons averaged at least 20 minutes over their scheduled time, with wide variation. Surgeons were infrequently completing cases at or below their requested case time. Most of the inaccuracy came from going long. The team used control charts to understand the impact of the change. The control charts showed that after the change in scheduling time, the 2 surgeons still went over their allotted case time, but to a lesser degree.

After gaining new information, the next step in the PDSA cycle is to determine the next test of change. The student team recommended sharing these data with the surgeons to consider next steps in improving block utilization, though time constraints of the semester limited continued involvement of the student team in the next PDSA cycle.

Discussion

Through the application of QI tools, new insight was gained about OR efficiency and potential improvements. The student team talked to numerous staff involved in scheduling and each discussion increased understanding of the issues that lead to OR inefficiency. The process map and fishbone diagram provided a visual expression of how small issues could impact the overall OR system. Application of QI tools also led the team to the discovery that surgeons may be interpreting case length in disparate ways, contributing to problems with scheduling.

Though the intervention did not have significant impact over 1 week, more time for subsequent PDSA cycles may have resulted in clinical improvements. Despite the limitations, the student team uncovered an important aspect of the block scheduling process, providing valuable information and insight for the department around this scheduling issue. The student team’s work was shared between multiple surgical departments, and the QI work in the department is ongoing.

Implications for Health Care Institutions

Nontraditional Projects Can Work

The issue of OR utilization is perhaps not a “traditional” QI project given the macro nature of the problem. Once it was broken down into discrete processes, problems such as OR turnover, scheduling redundancies, and others look much more like traditional QI projects. It may be beneficial to institutions to broaden the scope of QI to problems that may, at first glance, seem out of the realm of process mapping, fishbone diagramming, and SMART aims. QI tools can turn management problems into projects that can be tackled by small teams, creating an culture of change in an organization [13].

Benefits of Student Teams

There are clear benefits to the institution working with students. Our hospital-based team members found it beneficial to have independent observers review the process and recommend improvements. Students were able to challenge the status quo and point out inefficiencies that have remained due to institutional complacency and lack of resources. The hospital employees were impressed and surprised that the students found the misunderstanding about case length, and noted that it suggests that there may be other places where there are miscommunications between various people involved in OR scheduling. The students’ energy and time was supported by the QI expertise of the course instructors, and the practical knowledge of the hospital-based team members. Similar benefits have been noted by others utilizing collaborative QI educational models [14,15].

Benefits for Students

For the students on the team, the opportunity to apply QI concepts to the real world was a unique learning opportunity. First, the project was truly interdisciplinary. The students were from varied fields and they worked with schedulers, surgeons, and office managers providing the students with insight into the meaning and perspectives of interprofessional collaboration. The students appreciated the complexity and tensions of the OR staff who were working to balance the schedules of nurses, anesthesiologists, and other OR support staff. Additionally, interdisciplinary collaboration in health care is of increasing importance in everyday practice [16,17]. A strong understanding of collaboration across professions will be a cornerstone of the students’ credentials as they move into the workforce.

There is also value in adding real work experience to academics. The students were able to appreciate not only the concepts of QI but the actual challenges of implementing QI methodology in an institution where people had varying levels of buy-in. Quality improvement is about more than sitting at a whiteboard coming up with charts—it is about enacting actual change and understanding specific real-world situations. The hospital collaboration allowed the students to gain experience that is impossible to replicate in the classroom.

Limitations and Barriers

As noted in other academic-practice collaborations, the limitation of completing the project in one semester presents a barrier to collaboration; the working world does not operate on an academic timeline [14]. Students were limited to only testing one cycle of change. This part of the semester was disappointing as the students would have liked to implement multiple PDSA cycles. The OR managers faced barriers as well; they invested time in educating students who would soon move on, and would have to repeat the process with a new group of students. The department has continued on with this work, but losing the students who they oriented was not ideal.

The course instructors were flexible in allowing the project team to spend the majority of time breaking down the problem of OR block utilization into testable changes, which was the bulk of our work. However, the skill that the team was able to dedicate the least amount time to, testing and implementing change, is useful for the students to learn and beneficial for the organization. Moving forward, allowing teams to build on the previous semester’s work, and even implementing a student handoff, might be tried.

Future Directions

Although our intervention did not lead to sustained improvements in OR scheduling efficiency, our project demonstrates how QI tools can be taught and applied in an academic course to address a management problem. Research to specifically understand institutional benefits of academic-practice collaborations would be helpful in recruiting partners and furthering best practices for participants in these partnerships. Research is also needed to understand the impact of QI collaborative models such as the one described in this paper on improving interprofessional teamwork and communication skills, as called for by health care professional educators [16].

Corresponding author: Danielle O’Rourke-Suchoff, BA, Case Western Reserve University School of Medicine, Office of Student Affairs, 10900 Euclid Ave., Cleveland, OH 44106, dko@case.edu.

Financial disclosures: none.