P-616 Systematic review and meta-analysis of efficacy and safety of r-FSH biosimilars EMA-approved compared to reference r-FSH (follitropin alfa)
Bibliographic record
Abstract
Abstract Study question Are recombinant FSH biosimilars approved by the European Medicines Agency (EMA) comparable in efficacy and safety to the originator follitropin alfa? Summary answer Pooled analysis from studies comparing EMA-approved biosimilars with the reference product did not detect differences in efficacy or safety between these two gonadotropins. What is known already A biosimilar is, according to EMA, a biological medicine highly similar to another already approved (‘reference’), and are approved according to the same standards of quality, safety and efficacy. Their development and approval opens a window of opportunity to make IVF treatments more affordable for the general population. Two previous meta-analysis of phase III non-inferiority randomized controlled trials (RCT) including non EMA-approved rFSH biosimilars (Chua et al., 2021 and Budani et a., 2021) have suggested that pregnancy and live births are lower with biosimilars compared to follitropin alfa. Study design, size, duration Systematic review with meta-analysis following PRISMA guidelines. Participants/materials, setting, methods Databases searched from inception to november 2021 were: PubMed-MEDLINE, WOS, The Cochrane Library, ClinicalTrials.gov, EudraCT and Google Scholar using these keywords: ‘biosimilars’, ‘follitropin alfa’, `originator’ and ‘ovarian stimulation’. RCTs and non-randomized comparative studies were included. Risk of bias was assessed with ROB-2 tool and Newcastle-Ottawa Scale studies. Pooled Odds Ratios (OR) and mean differences (MD) when applicable, with a 95% confidence interval (CI), were calculated. PROSPERO protocol registration has been requested. Main results and the role of chance After the systematic search,five studies were included in the meta-analysis: two phase-III RCT (Strawitzki, 2016 and Rettenbacher, 2015) and three non-randomized comparative studies, one of them prospective (Kaplan 2021) and the other two retrospective (Sprem Goldstajn, 2021 and Van den Haute, 2021) involving 2173 IVF cycles. Risk of bias was low for the two RCT and moderate for the observational studies. The OR of clinical pregnancy was 0.89 (95% CI = 0.74,1.07; I2=0%) and the OR of live birth was 0.86 (95% CI = 0.71,1.04; I2=0%). No differences were observed in the cumulative birth rate either (OR = 0.86; 95% CI = 0.68, 1.09; I2 0%). The total number of oocytes retrieved was similar (MD = 0.25; 95%CI,-0.93, 1.43; I2 79%); as it was the total dose of gonadotropins employed (MD=-19.56; 95% CI, -57.88, 18.76; I2 0%) and the length of the stimulation (MD = 0.12; 95% CI,-0.23, 0.47; I2 80%). The risk of Ovarian Hyperstimulation Syndrome was similar in both cases (OR = 1.36; 95% CI, 0.63, 2.91; I2 21%). Limitations, reasons for caution Main limitations of this meta-analysis include the fact that three of the five included studies are not randomized studies and two of them are retrospective, which can bias the results. Wider implications of the findings This is the first meta-analysis including only results from studies with biosimilars EMA-approved. The results show that there are no differences between the biosimilars and the reference in terms of efficacy or safety. Larger RCTs including patients with different patterns of ovarian response are needed to confirm these findings. Trial registration number Not applicable
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".