Pegfilgrastim OBI device use for neutropenia prevention: a scoping review

This is a scoping review based on the JBI methodology. Only studies with adults with cancer undergoing outpatient chemotherapy were included. The search was carried out in the Cochrane, CINAHL, EMBASE, LILACS, PubMed, Scopus, LIVIVO and Web of Science databases, in addition to gray literature ProQuest, SciELO, Database in Nursing, Google Scholar, Open Grey, drug leaflet and websites. The searches in the references of selected studies were exhausted. All identified studies were exported to the EndNote reference manager for organization and removal of duplicates. The Rayyan web application was used for evidence selection. The studies were selected by pairs independently, with conflicts resolved by a third researcher.

Results

A total of 10 articles were included, whose results were subdivided into categories: patient compliance, health team opinion, patient workload in cancer treatment and device use in clinical practice. The device has few flaws and was accepted by health care teams and patients in most studies.

Conclusion

The main health care for Pegfilgrastim On-body Injector use is related to the skin preparation technique where the device will be applied, in addition to device preparation and administration. Moreover, the importance of assessing the knowledge of patients and their family about the device is highlighted, providing all the necessary guidelines, verbally and in writing, clearly and objectively, and validating this information, making sure that patients have understood all of them and are safe.

Neutropenia; Chemotherapy-induced febrile neutropenia; Evidence-based practice; Filgrastim; Antineoplastic agents; Neoplams

Category 1- Patient experience and opinion regarding Pegfilgrastim OBI use
Author	Objective	Method	Population	Results
Lisa S. (2016) ( ¹⁵15. Ruef C , Sabol L . Evaluating the On-Body Injector for Neulasta ® as an alternative to manual Neulasta® Injection . Oncology Nursing Forum . 2016 ; 43 ( 2 ): 14 . ) USA	Test the safety and efficacy of Pegfilgrastim OBI in an infusion center and educate the nursing team to manage the device.	Pilot study. Nursing team training with a practical demonstration on how to handle the device. Patients received an information leaflet to read, watched a video and were followed up 48 hours after OBI infusion to ensure the success of the injector. Laboratory tests were obtained one week later.	25 patients on outpatient chemotherapy.	The injector was successful in all participants. An incomplete dose was delivered to one patient and three patients were hospitalized within a week of Neulasta injection. None of these events were considered injector related.
Saif et al. (2019) ( ¹⁶16. Saif MW , Hackenyos DW , Smith MH , Healey P , Relias V , Wasif K . Racial differences in accepting Pegfilgrastim Onpro Kit (On-Body Injector) use among cancer patients . Clin Oncol . 2019 ; 1 ( 6 ): 1026 . ) USA	Assess the acceptance of the Onpro kit among patients undergoing chemotherapy.	Descriptive, retrospective study with patients who received the Onpro kit within 1 hour of completion of systemic chemotherapy. Nursing notes and pharmacy records were reviewed to identify patients who refused the Onpro kit and to discern reasons for refusal, including racial reason.	Patients with gastrointestinal tumors undergoing G-CSF.	Five of 68 patients refused the kit (22%), of which 87% were Asian. Reasons for refusal included: aversion to bulky compliance with the skin, understanding about unwitnessed medication administration, fear of reaction, disposal at home, fear of pain, and lack of confirmation of proper dose administration.
Category 2: Patient and health team experience and opinions regarding Pegfilgrastim OBI use
Author	Objective	Method	Population	Results
Brett Hauber et al. (2018) ( ¹⁷17. Brett Hauber A , Mange B , Price MA , Wolin D , Bensink M , Kaye JA , et al . Administration options for pegfilgrastim prophylaxis: patient and physician preferences from a cross-sectional survey . Support Care Cancer . 2018 ; 26 ( 1 ): 251 - 60 . ) Germany	Estimate patient and physician preferences Pegfilgrastim administration options and the relative importance of the resources associated with these options to to determine systematic variations in physicians’ preferences according to patients’ profile.	Cross-sectional. Application of a multiple-choice data collection instrument about Pegfilgrastim administration options.	200 patients and 200 physicians prescribing G-CSF	Most patients (77.5%) preferred to receive application at the clinic and 16% of patients chose the OBI. Patients generally preferred the administration option with which they had experience: 48.5% of patients who received prior injections at the clinic chose this route and 56.8% with prior OBI administration preferred this option. For the most clinically committed patient with a longer travel distance to the clinic, 37.5% of physicians preferred in-clinic application and 49.5% preferred the OBI. For the less clinically compromised patient and with the shortest travel distance to the clinic, 55.5% of physicians preferred application in the clinic, and 28%, the OBI.
Metz et al. (2021) ( ¹⁸18. Metz M , Semsek D , Rogmans G , Hutzschenreuter U , Fietz T , Harde J , et al . Patient, nurse, and physician preferences: final results of the CONVENIENCE study evaluating pegfilgrastim prophylaxis via pre-filled syringe or on-body injector in cancer patients . Support Care Cancer . 2021 ; 29 ( 11 ): 6633 - 43 . ) Germany	Assess patient, nurse, and physician preferences as well as health care economics, for administering Pegfilgrastim with OBI or manually using a pre-filled syringe (OS).	Randomized, crossover, non-blinded, two-arm clinical trial. Patients with breast cancer x patients with non-Hodgkin’s lymphoma, 1:1, were randomized to receive Pegfilgrastim for four consecutive cycles of chemotherapy in an alternating sequence, starting with OBI or pre-filled syringe. The primary outcome was patient preference assessed by questionnaires.	308 patients with early-stage breast cancer receiving anthracycline/cyclophosphamide or taxane-based chemotherapy, and patients with non-Hodgkin’s lymphoma receiving first-line R-CHOP.	Patients preferred OBI over pre-filled syringe (OBI 43.2%; vs. pre-filled syringe 36.0%), but the difference was not statistically significant. Among patients with preference for OBI, saving time was the main reason for preference. Both arms of the study showed the same results, indicating that patients’ preference is independent of application sequence. Study nurses slightly preferred the pre-filled syringe (n = 19, 46.3%) over the OBI (n = 18, 43.9%) Physicians clearly preferred the pre-filled syringe (n = 24, 58.8%) over the OBI (n = 15, 36.6%).
Mahler et al. (2017) ( ¹⁹19. Mahler LJ , DiBlasi R , Perez A , Gaspard J , McCauley D . On-body injector: an administration device for pegfilgrastim . Clin J Oncol Nurs . 2017 ; 21 ( 1 ): 121 - 22 . ) USA	Monitor the execution Onpro delivery system in an oncology clinic.	A satisfaction survey was carried out with patients.	38 patients with cancer using Pegfilgrastim OBI and nursing staff from the oncology clinic.	Of 38 participants, 6 reported a problem using the OBI. On a scale of 1 (not satisfied) to 5 (extremely satisfied), 32 patients rated their satisfaction as 4 or 5, and only 2 were dissatisfied with the OBI. Nurses had no difficulties in placing the device. Failed devices were returned by patients and replaced under the Amgen ^® refund program. There was an improvement in the clinic’s workflow.
Yucel et al. (2021) ( ²⁰20. Yucel A , Skalicky A , Eseyin OR , Yucel E , Belani R , Bensink M . Development and content validation of the Satisfaction and Experience Questionnaire for Granulocyte Colony-Stimulating Factor (SEQ-G-CSF) . J Patient Rep Outcomes . 2021 ; 5 ( 1 ): 10 . ) USA	Develop a Satisfaction and Experience Questionnaire for G-CSF (SEQ-G-CSF) to help understand perspectives and patient satisfaction with different G-CSF options.	Descriptive study with a qualitative approach. All patients were receiving prophylaxis with G-CSF via injection or OBI. The sample was divided into 2 groups, with group 1 comprising 20 participants with previous experience using Pegfilgrastim OBI and group 2 comprising 20 participants with no prior experience. Both participated in focus groups conducted by video with online calls and semi-structured discussions.	Three oncology nurses and 40 adult patients with cancer, 10 with breast cancer, 10 with lung cancer, 10 with non-Hodgkin’s lymphoma and 10 with prostate cancer.	Discussing their experience and satisfaction with the G-CSF, 53% of patients and 29% of participants highlighted the benefits of using the OBI, including convenience, ease of use, available support, and reduced travel and time overhead. The most cited negative experiences were adverse events (lethargy and fatigue) and the need to undergo additional treatment. The SEQ-G-CSF included five domains involving overall satisfaction (one item), treatment burden (four items), travel burden (two items), time burden (four items), and compliance with treatment (two items). Nurses reported that patients tend to tolerate adverse treatment events when they see improvement or if their quality of life is not significantly impacted.
Category 3 - Workload of patients undergoing cancer treatment
Author	Objective	Method	Population	Results
Cheng et al. (2019) ( ²¹21. Cheng AC , Levy MA . Measures of treatment workload for patients with breast cancer . JCO Clin Cancer Inform . 2019 ; 3 : 1 - 10 . ) USA.	Assess dimensions of treatment workload related to outpatient visits, commuting, and admissions.	Descriptive, quantitative study. The authors developed measures to measure the workload of the days when patients go to the health service for treatment and their displacement. They then applied these methods to two populations of breast patients with cancer to determine whether the measures were sensitive to differences in disease stage and treatment protocols.	Women at different stages and undergoing treatment for breast cancer.	Patients with more advanced cancers experienced a greater treatment workload. In the first 18 months after diagnosis, patients with stage III disease spent a median of 81 hours in outpatient clinics, 61 hours in commuting time, and spent $1.432 in commuting costs. In contrast, patients with stage I disease spent an average of 29 hours in the clinic, 34 hours in travel time, and $834 in travel costs. Authors emphasize that Pegfilgrastim OBI was effective in reducing some dimensions of the workload for these patients, such as, for example, the time in days that patients stay in the clinic and the need for additional visits.
Category 4 - Pegfilgrastim OBI use in clinical practice
Author	Objective	Method	Population	Results
Patel et al. (2019) ( ²²22. Patel J , Rainess RA , Benfield MJ , Rogers KM , Moore DC , Larck C , et al . Retrospective analysis of clinical outcomes associated with the use of pegfilgrastim on-body injector in patients receiving chemotherapy requiring granulocyte colony-stimulating factor support . Hosp Pharm . 2021 ; 56 ( 2 ): 77 - 80 . ) USA	Assess the incidence of febrile neutropenia in patients receiving Pegfilgrastim OBI.	Observational, descriptive and quantitative study. A retrospective review of electronic medical records of adult patients with cancer who received chemotherapy and Pegfilgrastim OBI was performed. Before a patient receives the OBI device, the nursing staff has been educated and trained. The primary outcome was the development of febrile neutropenia. Secondary outcomes included Pegfilgrastim OBI device failure and treatment delays or dose modifications secondary to febrile neutropenia or neutropenia event. Patients were followed for up to 30 days after the last chemotherapy administration to assess the occurrence of any study parameters.	28 adult patients with cancer on myelosuppressive chemotherapy.	Pegfilgrastim OBI were administered during the study period. All patients received Pegfilgrastim OBI as primary prophylaxis and none of the participants developed febrile neutropenia. There were no treatment delays or changes in chemotherapy dose secondary to a febrile neutropenia or neutropenia event. - There were two device failures (1.92%). Failure 1: A patient observed a malfunction in the device’s indicator light, yet received the full dose. Failure 2: The Pegfilgrastim dose was not administered correctly, and it was reported that the Pegfilgrastim leaked down patients’ arm. One case of anaphylaxis has been reported after receiving Pegfilgrastim OBI.
Mahtani et al. (2022) ( ²³23. Mahtani RL , Belani R , Crawford J , Dale D , DeCosta L , Gawade PL , et al . A prospective cohort study to evaluate the incidence of febrile neutropenia in patients receiving pegfilgrastim on-body injector versus other options for prophylaxis of febrile neutropenia: breast cancer subgroup analysis . Support Care Cancer . 2022 ; 30 ( 7 ): 6135 - 44 . ) USA	Assess the incidence of febrile neutropenia in patients who received treatment with curative intent, patients undergoing chemotherapy with delays or dose reduction and compliance with the device.	Prospective, multicenter cohort study. Patients were followed from baseline until death, discontinuation of chemotherapy, withdrawal of consent, loss to follow-up, or termination of the study.	Patients with cancer receiving myelosuppressive chemotherapy treatment and at high risk of developing febrile neutropenia.	In all cycles, the incidence of febrile neutropenia was lower in patients receiving Pegfilgrastim OBI (4.4% [95% CI, 3.3 5.6%]) compared to those who received other options (7.4% [95% CI 5.3–9.6%]. The OBI group had a lower incidence of febrile neutropenia in each cycle. In patients receiving treatment with curative intent, the incidence of febrile neutropenia in all cycles was lower in those receiving Pegfilgrastim OBI (4.6% [95% CI, 3.4 5.8%]; across all cycles, the percentage of patients on chemotherapy with delays or dose reductions was 4.7% (95% CI, 3.5 5.9%) for the OBI group and 4.7% (95% CI, 2.9-6.4%) for the other group. Adherence to G-CSF was higher in patients receiving Pegfilgrastim OBI (93.8% [CI 95%, 92.5–95.2%]) compared to those receiving other options (69.8% [CI 95 %, 66.1–73.6%]).
McBride et al. (2021) ( ²⁴24. McBride A , Campbell K , Li E , Schroader B , Campbell D , Wang W . Economic and clinical outcomes of pegfilgrastim via prefilled syringe vs on-body injector: a real-world data analysis . J Manag Care Spec Pharm . 2021 ; 27 ( 9 ): 1230 - 8 . ) USA	Compare effectiveness and economic outcomes of Pegfilgrastim in pre-filled versus OBI presentations.	Retrospective cohort study. A propensity score was used to match pre-filled syringe cohort 1:1 to OBI. The results were compared between the matched cohorts using estimation equations.	3.152 patients with breast diagnosis cancer or non-Hodgkin’s lymphoma that received myelosuppressive chemotherapy and prophylactic use of Pegfilgrastim via pre-filled syringe or OBI.	1088 patients received prophylaxis with Pegfilgrastim OBI and 2064 received pre-filled syringe. Rates of febrile neutropenia within each Pegfilgrastim cohort were low. During the first cycle of chemotherapy, there was no statistically significant difference in the incidence of febrile neutropenia between the OBI or pre-filled syringe cohorts (1.01% [95% CI = 0.56-1.82] versus 1.48% [95% CI = 0.91-2.39], respectively; p = 0.336). When considering all chemotherapy cycles (total cycles = 7.467), there was also no difference in the incidence of febrile neutropenia between the OBI or pre-filled syringe cohorts (0.91% [95% CI = 0.64-1.30] vs 1.22% [95% CI = 0.90-1.64], respectively; p= 0.214).

Information for patients using the Pegfilgrastim OBI device	Precautions when applying the Pegfilgrastim OBI device for health professionals
ABOUT THE DEVICE	ASSESSMENT
Pegfilgrastim OBI (NEULASTA) is a smart device placed on your skin (belly or upper arm) that delivers the exact dose of its medication automatically and at the correct time. After your chemotherapy infusion is finished, nurses will stick the device to your skin and you can go home. After 27 hours, the prescribed dose will be applied automatically.	Knowledge assessment: Assess what patient and family member know about the device; Assess conditions of sanitation and personal hygiene; Have an enlightening conversation about device care. skin assessment Do not apply to scars, wounds and moles; in case of excess hair, trim with scissors before application; Do not fix close to ostomies and/or hernias.
AT THE CLINIC PREPARATION AND TRAINING	PREPARATION
Nurses will prep your skin and glue the pre-filled device. It is critical that you have a full view of the device, and if it is taped behind your arm, you need a caregiver who can watch it at all times. Nurses will train you, explaining the precautions and the light and sound signals that the device emits: Status light: Flashing Green: Body injector is working properly, do not remove. Steady green: the medication has been injected, check if the volume is set to “empty”. Flashing red: Device error. Contact the infusion clinic and talk to nurses. Volume indicator: Shows the amount of medication inside the device (full or empty).	Preparing the medication: 1. Remove the medication from the refrigerator (it must be stored under refrigeration at 2ºC to 8ºC). Wait 30 minutes and remove the syringe from the wrapper; 2. Remove the needle cap; 3. Insert the needle at a 90º angle into the medication port and push the plunger until all the contents are deposited in the device. CAUTION: During inflation, a “beep” will sound and the body injector will activate. After activation, you have 3 minutes to: complete steps 4, 5 and 6 and apply to patients; 4. Check if the marker is in “full”; 5. Remove the blue security seal; 6. Peel off the two patches and prepare to attach to patients. The device is ready to be applied to properly assessed and prepared skin.
AT THE CLINIC BEFORE YOU GO HOME:	APPLICATION
Have the contact of the clinic/health team so that you can call immediately with any questions or errors. When should I call my physician/nurse? · If you have any allergic reaction at the site of fixation; · If you feel any reaction during/after application, such as: redness in the body, shortness of breath, dizziness, swelling in the lips and eyes, excessive sweating, racing heart, itching or fever; · If you feel pain in the upper left part of your stomach or at the tip of your left shoulder; · If the team does not answer you quickly, look for the emergency service	1. Choose location: The device can be applied on the left and right sides of the abdomen at a distance of 5 cm from the navel or on the back of the arm, as long as you have a caregiver/family member to observe the site. 2. Prepare the skin: After choosing the location, perform skin antisepsis with cotton and 70% alcohol, ensuring that the site is clean. Wait for it to dry before adhering the device. 3. Apply the device: On the back of the upper arm, the status light should face down. On the abdomen, the status light should be facing the navel. 4. Make sure it is correct: A beep will inform you that the cannula is about to be inserted. A long beep will sound and the status light will turn green. This means the cannula has been inserted.
AT HOME APPLICATION, WITHDRAWAL AND IMPORTANT CARE:	MONITORING
· 26 hours after placement of Neulasta, find a comfortable place to wait for application; · At the 27 ^th hour prepare for application; · When starting application, the device will emit a sound warning and a green light will “flash”; · For 45 minutes the medicine will be administered; · When finished, you will hear a “BEEP” sound and the green light will stop flashing; · Check if the tag is on “empty”. If so, everything worked. · Wait for another 1 hour to ensure complete application. · That is it, you can now remove the device and throw it in the specific trash that was delivered to you. If the device beeps and emits a RED light and/or remains “full”. CALL YOUR NURSE OR PHYSICIAN. · Do not rub the device (blouse/belt); · Do not stay in temperatures lower than 5°C or higher than 40°C; · Do not expose the device directly to the sun; · Do not sleep on top of the device; · Do not remove the adhesive before application; · Do not apply creams and perfumes near the site; · Do not expose the device to: radiotherapy, tomography, magnetic resonance imaging, ultrasound and X-ray; · Keep the device 10 cm away from electronics and microwaves; · Traveling by plane: No problem, as long as you are not flying at the time of application (between the 24 ^th hour and 1 hour after the end). The device must not pass through the metal detector. Ask your physician for a report and TSA card. Taking a shower: Do not take a bath in the bathtub, sauna or swimming pools. Shower within the first 24 hours after putting on the device to allow time for the dressing to dry during application.	· Error or failure when applying: · If it beeps continuously for 5 minutes and the status light is flashing red, remove the On -body Injector from patients and attach another one. · In all occurrences of error, it is important that patients flag it and you speak with the Amgen representative in your region who will assist you and provide the refund. · End care and navigation in oncology · Deliver in writing to patients the final time at which the injector was applied in the body, what is the expected start and end time of application; · Provide the telephone number of the clinic/physician/nurse; · Reinforce in which situations patients should seek the emergency unit; · If possible, contact the emergency team where patients are referred and explain about the device; · Review each step of patient care guidelines; · Give patients instructions to take home; · Before patients go home, make sure they understand all the information and are safe; · Monitor patients via teleservice the next day to find out how the device is being fixed and reinforce care; · Perform a teleservice on the second day to check if the dose has been delivered. This step is essential for patient safety.

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[1] Corresponding author: Renata Cristina de Campos Pereira Silveira E-mail: recris@eerp.usp.br