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The emergence of the precision medicine paradigm in oncology has led to increasing interest in the integration of real-world data (RWD) into cancer clinical research. As sources of real-world evidence (RWE), such data could potentially help address the uncertainties that surround the adoption of novel anticancer therapies into the clinic following their investigation in clinical trials. At present, RWE-generating studies which investigate antitumour interventions seem to primarily focus on collecting and analysing observational RWD, typically forgoing the use of randomisation despite its methodological benefits. This is appropriate in situations where randomised controlled trials (RCTs) are not feasible and non-randomised RWD analyses can offer valuable insights. Nevertheless, depending on how they are designed, RCTs have the potential to produce strong and actionable RWE themselves. The choice of which methodology to employ for RWD studies should be guided by the nature of the research question they are intended to answer. Here, we attempt to define some of the questions that do not necessarily require the conduct of RCTs. Moreover, we outline the strategy of the European Organisation for Research and Treatment of Cancer (EORTC) to contribute to the generation of robust and high-quality RWE by prioritising the execution of pragmatic trials and studies set up according to the trials-within-cohorts approach. If treatment allocation cannot be left up to random chance due to practical or ethical concerns, the EORTC will consider undertaking observational RWD research based on the target trial principle. New EORTC-sponsored RCTs may also feature concurrent prospective cohorts composed of off-trial patients. • The role of real-world data (RWD) in cancer clinical research is increasing. • A false dichotomy exists between RWD studies and randomised controlled trials (RCTs). • There are different methodologies for RWD studies, including RCT designs. • The methodology to be employed should be determined by the research question. • We outline the RWD strategy of a large academic clinical cancer research organisation. [ABSTRACT FROM AUTHOR]

The Food and Drug Administration and European Medicines Agency typically approve market access for cancer drugs based on surrogate end-points, which do not always translate into substantiated improvements in outcomes that matter the most to patients, i.e. survival and quality of life. These drugs often, also, have a high price tag. We assessed whether there was an increase in cancer drug expenditure for a broad selection of indications, and whether this correlates with increased overall survival. This cohort study used Belgian Cancer Registry data from 125,692 patients (12 cancer indications, incidence period 2004–2017), which was linked to reimbursement and survival data. This reliably represents the Belgian situation. One-to-five year observed survival probability, median survival time, oncology drug expenditure and mean oncology drug cost per patient were reviewed. In almost all indications, total expenditure and average treatment cost for oncology drugs increased over the years (2004–2017). In contrast, mixed findings are observed for the evolution in overall survival probability and median survival time. While an absolute improvement in the 3-year survival probability of about 10% is noticed in non-small-cell lung cancer and chronic myeloid leukaemia, improvements in about half of the other indications are limited or even absent. The Belgian observational data indicate that assuming 'innovative' oncology drugs always add value in terms of improved survival is often unjustified. The literature also highlights the problem of using surrogate end-points, and the lack of comparative evidence showing an added value of oncology drugs for both survival and quality of life at market approval or during the post-marketing phase. Comparative studies should be conducted in the pre-marketing phase that are suitable for registration purposes, aid reimbursement decisions and support physicians and patients when making treatment decisions. • Food and Drug Administration and European Medicines Agency typically approve cancer drugs based on surrogate end-points. • Overall survival (OS) and quality of life data are often not available to decision makers. • Evolution in OS and drug expenditure (12 cancer types, 125 692 patients) is described. • Substantial increases in drug expenditure often do not coincide with clear OS gains. • Comparative pre-marketing studies should include OS and quality of life as patient-relevant outcomes. [ABSTRACT FROM AUTHOR]

Because it spares many normal tissues and reduces the integral dose, proton therapy (PT) is the preferred tumor irradiation technique for treating childhood cancer. However, to the best of our knowledge, no systematic review of the clinical effectiveness of PT in children has been reported in the scientific literature. A systematic search for clinical outcome studies on PT published between 2007 and 2015 was performed in Medline (through OVID), EMBASE, and the Cochrane Library. Twenty-three primary studies were identified, including approximately 650 patients overall. The median/mean follow-up times were limited (range, 19-91 months). None of the studies were randomized, 2 were comparative, and 20 were retrospective. Most suffered from serious methodologic limitations, yielding a very low level of clinical evidence for the outcomes in all indications. For example, for retinoblastoma, very low-level evidence was found that PT might decrease the incidence of second malignancies. For chondrosarcoma, chordoma, craniopharyngioma, ependymoma, esthesioneuroblastoma, Ewing sarcoma, central nervous system germinoma, glioma, medulloblastoma, osteosarcoma, and rhabdomyosarcoma, there was insufficient evidence to either support or refute PT in children. For pelvic sarcoma (ie, nonrhabdomyosarcoma and non-Ewing sarcoma), pineal parenchymal tumor, primitive neuroectodermal tumor, and "adult-type" soft tissue sarcoma, no studies were identified that fulfilled the inclusion criteria. Although there is no doubt that PT reduces the radiation dose to normal tissues and organs, to date the critical clinical data on the long-term effectiveness and harm associated with the use of PT in the 15 pediatric cancers under investigation are lacking. High-quality clinical research in this area is needed. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: The estimation of herpes zoster (HZ) vaccine efficacy by time since vaccination and age at vaccination is crucial to assess the effectiveness and cost-effectiveness of HZ vaccination. Published estimates for the duration of protection from the vaccine diverge substantially, although based on data from the same trial for a follow-up period of 5years. Different models were used to obtain these estimates, but it is unclear which of these models is most appropriate (if any). Only one study estimated vaccine efficacy by age at vaccination and time since vaccination combined. Recently, data became available from the same trial for a follow-up period of 7years. Aim and methods: We aim to elaborate on estimating HZ vaccine efficacy (1) by estimating it as a function of time since vaccination and age at vaccination, (2) by comparing the fits of a range of models, and (3) by fitting these models on data for a follow-up period of 5 and 7years. Results: Although the models’ fit to data are very comparable, they differ substantially in how they estimate vaccine efficacy to change as a function of time since vaccination and age at vaccination. Discussion: An accurate estimation of HZ vaccine efficacy by time since vaccination and age at vaccination is hampered by the lack of insight in the biological processes underlying HZ vaccine protection, and by the fact that such data are currently not available in sufficient detail. Uncertainty about the choice of model to estimate this important parameter should be acknowledged in cost-effectiveness analyses. [Copyright &y& Elsevier]

Summary: Since its introduction more than a decade ago, intensity-modulated radiotherapy (IMRT) has spread to most radiotherapy departments worldwide for a wide range of indications. The technique has been rapidly implemented, despite an incomplete understanding of its advantages and weaknesses, the challenges of IMRT planning, delivery, and quality assurance, and the substantially increased cost compared with non-IMRT. Many publications discuss the theoretical advantages of IMRT dose distributions. However, the key question is whether the use of IMRT can be exploited to obtain a clinically relevant advantage over non-modulated external-beam radiation techniques. To investigate which level of evidence supports the routine use of IMRT for various disease sites, we did a review of clinical studies that reported on overall survival, disease-specific survival, quality of life, treatment-induced toxicity, or surrogate endpoints. This review shows evidence of reduced toxicity for various tumour sites by use of IMRT. The findings regarding local control and overall survival are generally inconclusive. [Copyright &y& Elsevier]

The tolerability and immunogenicity of the hepatitis C virus E1 protein as a candidate vaccine was examined in a Phase I, single-arm study. Twenty healthy male volunteers were injected in the deltoid muscle at weeks 0, 3 and 6 with 20 μg recombinant E1 adsorbed on alum. A fourth (booster) dose was administered to 19 subjects at week 26. The candidate therapeutic vaccine was well tolerated. Three vaccine doses induced a clear humoral anti-E1 response that was boosted by a fourth dose. A strong, specific cellular immune response towards E1 was elicited in all vaccine recipients, which included a clear Th1 type response in all but one of the subjects. [Copyright &y& Elsevier]

Starting from historic reflections, the current SARS-CoV-2 induced COVID-19 pandemic is examined from various perspectives, in terms of what it implies for the implementation of non-pharmaceutical interventions, the modeling and monitoring of the epidemic, the development of early-warning systems, the study of mortality, prevalence estimation, diagnostic and serological testing, vaccine development, and ultimately clinical trials. Emphasis is placed on how the pandemic had led to unprecedented speed in methodological and clinical development, the pitfalls thereof, but also the opportunities that it engenders for national and international collaboration, and how it has simplified and sped up procedures. We also study the impact of the pandemic on clinical trials in other indications. We note that it has placed biostatistics, epidemiology, virology, infectiology, and vaccinology, and related fields in the spotlight in an unprecedented way, implying great opportunities, but also the need to communicate effectively, often amidst controversy. [ABSTRACT FROM AUTHOR]