Eur J Hosp Pharm: first published as 10.1136/ejhpharm-2021-eahpconf.15 on 14 March 2021. Downloaded from Abstracts patients). The potential percentage of use was about 17% of recommendation (score 3 points) of clinical applicability was the total. DOR+FTC/TAF or DOR+FTC/TDF represented a reached for clinical status at day 11. cost of 851.55C¼ and 642.90C¼ /patient/month, respectively. Conclusion and relevance No differences were found between RVP/FTC/TAF, EFV/FTC/TDF or DRV/COBI/FTC/TAF would early and late use of remdesivir in COVID-19. We developed cost 673.57, 262.58 or 857.51C¼ /patient/month, respectively. the first study with a systematic review and methodology Conclusion and relevance DOR would be beneficial in those about subgroup analysis of timing of use of remdesivir. patients with CNS disorders due to EFV and high viral load (>100 000 copies) or in polymedicated patients because of REFERENCES AND/OR ACKNOWLEDGEMENTS ’ the lower profile of interactions. In the remaining cases, there 1. Sun X, et al. How to use a subgroup analysis: users guide to the medical litera- ture. JAMA 2014;311:405–11. are alternatives already available in the hospital (following rec- 2. Gil-Sierra MD, et al. Checklist for clinical applicability of subgroup analysis. J Clin ommendations of the GESIDA guidelines). Pharm Ther 2020;45:530–8.

REFERENCES AND/OR ACKNOWLEDGEMENTS Conflict of interest No conflict of interest

Conflict of interest No conflict of interest 2SPD-032 NETWORK META-ANALYSIS OF THERAPEUTIC ALTERNATIVES IN UNTREATED METASTATIC 2SPD-031 SUBGROUP ANALYSIS ABOUT EFFICACY OF EARLY SQUAMOUS NON-SMALL CELL LUNG CANCER USE OF REMDESIVIR IN COVID-19 1MDP Briceño Casado*, 2S Fenix-Caballero, 3V Gimeno-Ballester, 2M Dominguez-Cantero, 1B De La Calle Riaguas, 2EJ Alegre-Del Rey. 1Hospital Nuestra Señora Del Prado, Hospital 1MD Gil-Sierra*, 2MDP Briceño-Casado, 3M Sanchez-Hidalgo, 3C Alarcon De La Lastra- Pharmacy, Talavera De La Reina, Spain; 2Hospital Universitario Puerto Real, Hospital Romero, 2B De La Calle-Riaguas, 4M Dominguez-Cantero, 5EJ Alegre-Del Rey. 1Hospital Pharmacy, Cadiz, Spain; 3Hospital San Jorge, Hospital Pharmacy, Huesca, Spain Doctor Jose Molina Orosa, Pharmacy, Arrecife, Spain; 2Hospital General Universitario Nuestra Señora Del Prado, Pharmacy, Talavera De La Reina, Spain; 3Universidad De Sevilla- 10.1136/ejhpharm-2021-eahpconf.15 Facultad De Farmacia, Pharmacology, Sevilla, Spain; 4Hospital Universitario De Puerto Real, Pharmacy, Puerto Real, Spain; 5Hospital Universitario De Puerto Real, Pharmacy, Sevilla, Background and importance Multiple therapeutic alternatives Spain are used in untreated metastatic squamous non-small cell lung – – 10.1136/ejhpharm-2021-eahpconf.14 cancer (umSNSCLC). Paclitaxel carboplatin pembrolizumab combination (PC-pembrolizumab) has recently been authorised Background and importance A greater benefit was suggested for this indication. with early treatment with remdesivir against COVID-19. Aim and objectives To assess the comparative efficacy among Aim and objectives To develop a systematic review and meth- different therapeutic alternatives used in mSNSCLC through a odological interpretation of subgroup analyses according to network meta-analysis (NMA). timing of use of remdesivir in COVID-19. Material and methods A search was conducted on 19 February Material and methods A bibliographic review in MEDLINE 2020 with the following inclusion criteria: phase II/III rando- was conducted up to 10 October 2020. The ‘Clinical Queries/ mised clinical trials (RCT), including drugs used in Narrow’ tool was used with the search strategy: ((Therapy/ umSNSCLC, and overall survival (OS) as the efficacy end- Narrow[filter]) AND (remdesivir AND COVID)). Randomised point. Exclusion criteria: mSNSCLC population with EGFR or clinical trials (RCTs) with subset analysis about early and late ALK mutations and RCTs without a comparator common to http://ejhp.bmj.com/ use of remdesivir (£10 vs >10 days from symptom onset, or the evaluated alternatives. Pooled hazard ratios (HR) were cal- £9 vs >9 days) were selected. The rest of the studies were culated by Bayesian methods, through the combination of excluded. All endpoints with subgroup analysis regarding tim- direct and indirect evidence by the NMA. Fixed and random ing of remdesivir use were assessed. Two methodologies were effects were evaluated. Deviance information criteria (DIC) sta- applied. The first considered statistical interaction among sub- tistics were used to compare the models. The agreement of sets, prespecification, biological plausibility and consistency of direct and indirect estimations was assessed by node splitting 1 the subgroup analyses of similar RCTs. The second methodol- models to evaluate the consistency of NMA. Delta value, max- on October 1, 2021 by guest. Protected copyright. ogy was a validated tool with preliminary questions to discard imum acceptable difference as clinical criterion of non-inferior- subset analysis without minimal relevance, and a checklist.2 ity, was set at 0.70 (and its inverse, 1.43), used to calculate This checklist assigned a score related to a recommendation the sample size in the PC-pembrolizumab trial. for applicability of subgroup analysis in clinical practice. Results Nine RCTs were selected. PC was the common compa- Results 20 results were found after review; 16 studies were rator. The DIC value for the fixed effects model was more excluded because they were not RCTs and 1 study had no favourable. No statistically significant differences between efficacy evaluation of remdesivir. Therefore, three RCTs were direct and indirect evidence were found, and therefore NMA selected. Endpoints considered were: time to clinical improve- was consistent. The PC-pembrolizumab combination was con- ment, mortality, viral load, and clinical status at days 11 and sidered as the reference (treatment with the greatest magni- 15. According to the first methodology, no statistical interac- tude of effect). HR for OS were: 1.4 (95% CI 0.89 to 2.3) tion was observed in the outcomes of the RCTs. Prespecifica- versus carboplatin–gemcitabine; 1.6 (1.2 to 2.1) versus PC; tion was established in time to clinical improvement, and 1.5 (1.1 to 2.1) versus nab–PC-atezolizumab; 1.8 (1.3 to 2.5) clinical status at day 15 of an RCT. Biological plausibility was versus PC-figitumumab; 1.4 (0.96 to 2.0) versus PC-motesa- described in the subset analysis of each endpoint of the RCTs. nib; 1.3 (0.66 to 2.5) versus PC-necitumumab; 2.1 (0.86 to No consistency of subgroup analyses were found. The second 5.0) versus PC-olaratumab; 2.9 (1.7 to 4.8) versus PC-sorafe- methodology discarded the applicability of the subset analysis nib and 1.2 (0.82 to 1.7) versus pembrolizumab monotherapy. through preliminary questions in two RCTs because of the Carboplatin–gemcitabine, PC-motesanib, PC-necitumumab, PC- absence of minimal relevance. For the third RCT, ‘null’ olaratumab and pembrolizumab did not present statistically

Eur J Hosp Pharm 2021;28(Suppl 1):A1–A184 A7 Eur J Hosp Pharm: first published as 10.1136/ejhpharm-2021-eahpconf.15 on 14 March 2021. Downloaded from Abstracts significant differences compared with PC-pembrolizumab. Stat- subset analysis in three RCTs. In the remaining RCT, a ‘null’ istically significant benefit was observed for PC-pembrolizumab recommendation was obtained for applicability of subgroup over PC, nab–PC-atezolizumab, PC-figitumumab and PC-sora- results because of inconsistency. fenib. According to the delta values, there could be clinically Conclusion and relevance Regarding the use of docetaxel in relevant differences among them. mHSPC, no consistent differences for OS were found in sub- Conclusion and relevance NMA showed no significant differen- set analysis according to VMD. Patients with low and high ces in OS between PC-pembrolizumab and carboplatin–gemci- burden mHSPC benefited from docetaxel therapy. This is the tabine, PC-motesanib, PC-necitumumab, PC-olaratumab and first study with a systematic review and methodology of sub- pembrolizumab in umSNSCLC, but there could be clinically group analyses in mHSPC according to VMD. relevant differences. PC, nab–PC-atezolizumab, PC-figitumumab and PC-sorafenib were inferior to PC-pembrolizumab, with REFERENCES AND/OR ACKNOWLEDGEMENTS ’ possible clinically relevant differences. 1. Sun X, et al. How to use a subgroup analysis: users guide to the medical litera- ture. JAMA 2014;311:405–11. 2. Gil-Sierra MD, et al. Checklist for clinical applicability of subgroup analysis. J Clin REFERENCES AND/OR ACKNOWLEDGEMENTS Pharm Ther 2020;45:530–8.

Conflict of interest No conflict of interest Conflict of interest No conflict of interest

2SPD-033 EVALUATION OF DOCETAXEL IN LOW AND HIGH 2SPD-034 USE OF DARATUMUMAB BASED TREATMENTS IN BURDEN METASTATIC HORMONE SENSITIVE PATIENTS WITH MULTIPLE MYELOMA AND HEPATIC PROSTATE CANCER IMPAIRMENT 1MD Gil-Sierra*, 2MDP Briceño-Casado, 3M Sanchez-Hidalgo, 3C Alarcon De La Lastra- 1MD Gil-Sierra*, 2S Fénix-Caballero, 3MDP Briceño-Casado, 4M Sánchez-Hidalgo, Romero, 2B De La Calle-Riaguas, 4M Dominguez-Cantero, 4EJ Alegre-Del Rey. 1Hospital 4C Alarcón De La Lastra-Romero, 3B De La Calle-Riaguas, 2M Dominguez-Cantero, Doctor Jose Molina Orosa, Pharmacy, Arrecife, Spain; 2Hospital General Universitario 2EJ Alegre-Del Rey. 1Hospital Doctor Jose Molina Orosa, Pharmacy, Arrecife, Spain; Nuestra Señora Del Prado, Pharmacy, Talavera De La Reina, Spain; 3Universidad De Sevilla- 2Hospital Universitario De Puerto Real, Pharmacy, Puerto Real, Spain; 3Hospital General Facultad De Farmacia, Pharmacology, Sevilla, Spain; 4Hospital Universitario De Puerto Real, Universitario Nuestra Señora Del Prado, Pharmacy, Talavera De La Reina, Spain; Pharmacy, Puerto Real, Spain 4Universidad De Sevilla-Facultad De Farmacia, Pharmacology, Sevilla, Spain

10.1136/ejhpharm-2021-eahpconf.16 10.1136/ejhpharm-2021-eahpconf.17

Background and importance Addition of docetaxel to hormonal Background and importance There are studies (subgroup analy- treatment in low and high burden metastatic hormone sensi- ses) suggesting a lack of benefit for daratumumab drug combi- tive prostate cancer (mHSPC) has raised important issues. nations in patients with untreated multiple myeloma (MM) There are studies suggesting increased overall survival (OS) in and hepatic impairment (HI). high burden disease and lack of benefit for low volume of Aim and objectives To conduct a systematic search and meth- metastases. odological interpretation of subset analysis about the use of Aim and objectives To perform a systematic search and meth- daratumumab based treatments in patients with untreated MM odological evaluation of subgroup analyses about the use of and HI. docetaxel in mHSPC according to volume of metastatic dis- Material and methods A bibliographic review in Pubmed was http://ejhp.bmj.com/ ease (VMD). performed up to 11 October 2020. A review strategy was Material and methods A systematic search in Pubmed was con- used in the ‘Clinical Queries/Narrow’ tool: (Therapy/Narrow ducted up to 25 September 2020. The following search strat- [filter]) AND (daratumumab AND myeloma). Randomised clin- egy was used in the ‘Clinical Queries/Narrow’ tool: (Therapy/ ical trials (RCTs) with subset analyses according to baseline Narrow[filter]) AND (docetaxel AND prostate cancer AND hepatic function for overall survival (OS) or progression free hormone sensitive). Randomised clinical trials (RCTs) with sub- survival (PFS) in untreated MM were selected. The rest of the

group analysis regarding VMD for OS were included. The search results were excluded. Two methodologies were on October 1, 2021 by guest. Protected copyright. rest of the review results were excluded. Two methodologies applied. One considered statistical interaction among subsets were used. One evaluated the heterogeneity of the subgroups (p<0.1), prespecification, biological support and consistency of (p<0.1), prespecification, biological support and consistency subset analyses of similar RCTs.1 The second methodology among subset analysis of similar RCTs.1 The second methodol- was a two part validated tool: preliminary questions to discard ogy was a validated tool made up of preliminary questions to subgroup analyses without minimal relevance, and a checklist.2 discard subgroup analyses without minimal relevance and a The checklist assigned a recommendation for applicability of checklist.2 This checklist provided recommendations of applic- subset analysis in clinical practice. ability for subgroup results. Results A total of 25 results were found in the search and the Results There were 31 results in the search and the following following were excluded: 10 were not RCTs, 9 studies had a were excluded: 9 were not RCTs, 13 did not evaluate the different clinical context, 2 evaluated different drugs and 1 effect of docetaxel, 4 had no subset analysis for VMD and 1 had no subset analysis. Therefore, three RCTs were included. did not assess OS. Therefore, four RCTs were included. According to the first methodology, statistical interaction According to the first methodology, heterogeneity among sub- among subsets was observed for PFS in one RCT. Subgroup groups was observed in one RCT. Subset analysis was prespe- analysis was prespecified in each endpoint of all RCTs. Biolog- cified in two RCTs. Biological support was found in the ical support could be reasoned for outcomes of subgroup anal- subgroup analyses of all RCTs. No consistency among results yses in all RCTs. However, no consistency of these subset of these subgroup analyses were observed. Preliminary ques- analyses was found. The second methodology (validated tool) tions of the second methodology discarded applicability of discarded applicability of subgroup analysis in two RCTs. In

A8 Eur J Hosp Pharm 2021;28(Suppl 1):A1–A184