
==== Front
Lancet Reg Health Eur
Lancet Reg Health Eur
The Lancet Regional Health - Europe
2666-7762
Elsevier

S2666-7762(24)00200-X
10.1016/j.lanepe.2024.101033
101033
Correspondence
Is the right answer always correct: between primary endpoint and clinical validity-author's reply
Birgin Emrullah emrullah.birgin@uniklinik-ulm.de
∗
Rahbari Nuh N. nuh.rahbari@uniklinik-ulm.de
∗∗
Department of General and Visceral Surgery, Ulm University Hospital, Ulm, Germany
∗ Corresponding author. emrullah.birgin@uniklinik-ulm.de
∗∗ Corresponding author. nuh.rahbari@uniklinik-ulm.de
14 8 2024
10 2024
14 8 2024
45 10103331 7 2024
6 8 2024
© 2024 The Author(s)
2024
https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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pmcWe thank Hoogteijing and colleagues1 for their interest in our recently published study. We reported the results of the first randomized controlled trial (RCT) comparing the outcomes of robotic hepatectomy (RH) versus laparoscopic hepatectomy (LH) for liver malignancies performed at a high-volume center.

Hoogteijing and colleagues addressed the clinical significance of quality of life (QoL) as primary endpoint and the research hypothesis. From the patients' perspective QoL remains one of the most—if not the most—important health value as it integrates all factors that affect patients’ well-being within a modern composite endpoint.2 In a previous study, we demonstrated that role functioning represents one of the most important health domains for oncological patients.3 Unfortunately, QoL is still highly underreported in surgical trials.3 This scarcity of data together with its high clinical relevance prompted us to choose QoL as primary endpoint.4 We hypothesized that the advantages of the robotic platform (e.g. visualization, degrees of freedom) enables more meticulous dissection that in turn might result in superior perioperative outcomes and ultimately improved QoL compared to laparoscopic surgery. Therefore, our sample size calculation was performed based on clinically meaningful differences on the QoL scale in line with other randomized trials using QoL as primary outcome.5 Thus, we believe that we met all defined prerequisites.

Hoogteijing and colleagues further point out that the benefit of QoL in previous trials might result from ‘smaller incisions and short-term benefits’ and cited three RCTs comparing minimally invasive to open hepatectomy: First, the LapOpHuva-trial demonstrated lower morbidity after LH but yielded no data on QoL. Second, the OSLO-COMET trial revealed also lower morbidity rates after LH and disclosed a significantly better QoL at 17 weeks using the SF-36 scale as secondary endpoint. However, QoL assessments were only available in 203 out of 294 patients. Third, the Orange II Plus trial showed faster perioperative recovery and a QoL benefit. However, the QoL benefit was not clinically meaningful (difference <10 points), while using the QLQ-C30 questionnaire in a mixed cohort of benign and malignant lesions, and to the best of our knowledge—the handling of missing data for QoL was not reported. These trials were not designed to elucidate the complex interaction between QoL and the surgical approach. Therefore, we believe that comparisons between two minimally invasive approaches with different number and locations of incisions, dissection devices and potentially different operating times, blood loss and complication rates are justified and important. This is in line with the growing interest comparing these approaches in various specialties. The Roc'n'Roll trial was therefore designed to close the evidence gap on the effect of RH on QoL with intensified QoL assessments.

The first robotic hepatectomy was performed 21 years ago. Even though it is well established that RCT remain the gold standard to evaluate effectiveness and safety of medical interventions, the Roc'n'Roll trial presents the first study to ever evaluate RH in a randomised controlled fashion. Importantly, it did so by using the most relevant clinical outcome parameter from the patients' perspective. Therefore, the question arises, if not the redundance of previous uncontrolled studies comparing RH to LH with their inherent risk of bias might rather constitute a significant ‘waste of time and resources’.6

The data of the Roc'n'Roll trial are of utmost significance to care providers, patients as well as the national health care systems. We consider the first publication of randomized data on the effectiveness and safety of RH as an increasingly applied medical intervention a significant contribution and ‘information to end-users’. Nonetheless, we fully agree that further multicenter trials are needed, particularly, with focus on long-term outcomes such as QoL.

Contributors

EB designed the ROC'N'ROLL trial, wrote the first draft, and performed surgical procedures in the trial. NNR supervised the ROC'N'ROLL trial, reviewed and edited the manuscript, and performed surgical procedures in the trial.

Declaration of interests

The authors declare no conflict of interest.

Acknowledgements

None.
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References

1 Hoogteijling T.J. SJ Abu Hilal M. Is the right answer always correct: between primary endpoint and clinical validity Lancet Reg Health Eur 2024 10.1016/j.lanepe.2024.101031
2 Gamper E.M. Petersen M.A. Aaronson N. Development of an item bank for the EORTC role functioning computer adaptive test (EORTC RF-CAT) Health Qual Life Outcomes 14 2016 72 27150974
3 Birgin E. Muller M. Woll C. Development of a conceptual framework to detect perioperative symptom burden following abdominal surgery for cancer Eur J Surg Oncol 49 9 2023 106933
4 Wilson M.K. Karakasis K. Oza A.M. Outcomes and endpoints in trials of cancer treatment: the past, present, and future Lancet Oncol 16 1 2015 e32 e42 25638553
5 Group TRS Laparoscopic or open abdominal surgery with thoracotomy for patients with oesophageal cancer: ROMIO randomized clinical trial Br J Surg 111 3 2024 znae023
6 Sijberden J.P. Hoogteijling T.J. Aghayan D. Robotic versus laparoscopic liver resection in various settings: an international multicenter propensity score matched study of 10.075 patients Ann Surg 280 1 2024 108 117 38482665
