Characteristics of Included Studies
A total of 13 records comprising 12 unique studies were eligible for inclusion (Table 1, Table S6, Figure S1). Seven studies were observational [33-39], alongside three interventional trials [40-42], and two budget impact models [43, 44]. Seven studies were conducted in Europe [33-35, 37, 39-41], two in the US, and one in Israel [36, 38, 42]. Both budget impact models used a UK perspective [43, 44]. Eight of the studies reported industry funding, all from Ipsen Biopharmaceuticals Inc. [34, 36, 37, 40, 41, 43, 44] or its subsidiary Tercica Inc. [42].
Five and six studies evaluated patients with acromegaly [34, 36, 38, 40, 42] and NETs, respectively [33, 35, 37, 39, 41, 44]. One of the budget impact models analyzed SSA usage in both acromegaly and NETs patient populations [43]. Most studies included fewer than 200 patients (18–184 patients), while one budget impact models estimated a population of 3,921 patients with acromegaly and 2,073 patients with NETs [43] (the other budget impact model did not report the size of the modelled population [44]). All patient characteristics are presented in Table S7.
Four studies assessed home injection only and did not include a comparison to injections administered in the healthcare setting [33, 35, 38, 42]. The majority of studies evaluated home injection of LAN only (7/12 studies) [33, 35, 36, 38, 40-42]. A further four studies investigated patients treated with LAN or OCT [37, 39, 43, 44]. One study did not specify which SSA treatment patients were administered [34].
Efficacy and Effectiveness Outcomes
Across the two indications, three clinical trials assessed treatment efficacy [40-42], and an additional three real-world evidence studies examined treatment effectiveness (Table 1 and Table S8) [36, 38, 39].
In patients with acromegaly, efficacy/effectiveness assessed by change in IGF-1 and GH values was similar in patients receiving home injections compared with injections in the healthcare setting, across two studies [36, 40]. Overall, >85% of participants receiving home injections were reported to achieve normalization or control of IGF-1 and GH in three studies (defined on the basis of study-specific thresholds; Table S8) [36, 38, 40].
In patients with NETs, comparable efficacy/effectiveness in the home and healthcare administration settings was also observed when assessing the proportion of patients with tumor progression, time to progression, and the proportion of participants with symptomatic control of diarrhea and flushing (n=2 studies) [39, 41].
Safety/Tolerability Outcomes and Treatment Adherence
Only three studies investigated the safety and tolerability of home injection, with a similar proportion of patients experienced adverse events (AEs) in both the home and healthcare administration settings (n=2 studies in acromegaly, n=1 study in NETs, Table 1 and Table S9) [36, 40, 41]. Of the two studies reporting injection site reactions, the first study showed no differences between self- or partner-injection and the healthcare administration setting, though statistical significance was not reported [40]. In the second study, a greater number of patients with acromegaly experienced injection site reactions following self-injection (19%) as compared with partner injections (2%; p<0.05) or injections in the healthcare setting (7%; statistical significance not reported) [36].
Adherence and successful administration rates were high in two studies reporting on patients with acromegaly [38, 40]. Across both studies, >90% of participants achieved either good adherence (>80% of expected injections) or successful administration of treatment as assessed by the study investigators [38, 40].
Patient-Reported Outcomes
Of the 12 included studies, 4 reported on patient preferences for setting of administration (Figure 1a, Table 1 and Table S10) [33, 34, 41, 42]. In patients with acromegaly, one study found that 82.6% of patients favored healthcare-setting administration, while another study reported that the majority (81.3%) of patients preferred self- or partner-administration to healthcare-setting administration [34, 42]. For studies assessing NETs, 88%–100% of patients preferred self- or partner-injection (n=2 studies) [33, 41].
A total of 75–100% of patients with receiving home injection were satisfied with their treatment or found it to be very/somewhat convenient at study end, compared to 38%–46% of patients for healthcare-setting administration (n=4 studies; Figure 1b, Table 1, and Table S10) [33, 35, 36, 42]. Fewer patients with NETs receiving self- or partner-injections (8%) reported that their treatment interfered with daily activities compared with those receiving injections in the healthcare setting (24%) [41].
Economic Outcomes
Home injection was associated with economic savings compared with healthcare-setting administration across six studies in patients with NETs (Table 1 and Table S11) [33, 35, 37, 41, 43, 44]. Direct cost savings were attributed to reduced healthcare resource use (n=4 studies) [37, 41, 43, 44]. Time saved by patients (including travel and attendance at appointments) was estimated to range from 1.4 hours to at least half a day per visit, with implications for indirect and out-of-pocket costs (n=3 studies) [33, 35, 41].
Two budget impact models estimated that the overall expenses would be cut by 16.4% or 9.1% per year in patients with GEP-NETs and acromegaly, respectively, if a patient treated in the healthcare setting with OCT switched to self- or partner-injections of LAN. In-hospital nurse contact and hospital visits would also be reduced in patients with gastroenteropancreatic (GEP)-NETs or acromegaly [43, 44].
Quality Assessment
A detailed summary of the quality assessment is provided in Table S12. Risk of bias varied between studies, with the reviewers finding six studies did not meet or provided insufficient information to determine ≥4/8 items of the modified Downs and Blacks checklist [36, 39, 40, 42-44]. Potential sources of bias identified related to both external and internal validity of included studies, including limitations in reporting such as details of the statistical analyses performed, recruitment of participants, and whether the participants were representative of the larger population.