Real-World Data and Randomised Controlled Trials: The Salford Lung Study

Real-world data (RWD), that is, data from sources other than controlled clinical trials, play an increasingly important role in medical research. The development of quality clinical registers, increasing access to administrative data sources, growing computing power and data linkage capacities have contributed to greater availability of RWD. Evidence derived from RWD increases our understanding of prostate cancer (PCa) aetiology, natural history and effective management. While randomised controlled trials offer the best level of evidence for establishing the efficacy of medical interventions and making causal inferences, studies using RWD offer complementary evidence about the effectiveness, long-term outcomes and safety of interventions in real-world settings. RWD provide the only means of addressing questions about risk factors and exposures that cannot be “controlled”, or when assessing rare outcomes. This review provides examples of the value of RWD for generating evidence about PCa, focusing on studies using data from a quality clinical register, namely the National Prostate Cancer Register (NPCR) Sweden, with longitudinal data on advanced PCa in Patient-overview Prostate Cancer (PPC) and data linkages to other sources in Prostate Cancer data Base Sweden (PCBaSe).

Download Full-text

Incorporating single-arm studies in meta-analysis of randomised controlled trials: a simulation study

BMC Medical Research Methodology ◽

10.1186/s12874-021-01301-1 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Janharpreet Singh ◽

Keith R. Abrams ◽

Sylwia Bujkiewicz

Keyword(s):

Simulation Study ◽

Randomised Controlled Trials ◽

Meta Analysis ◽

Health Technology ◽

Small Error ◽

Aggregate Data ◽

Controlled Trials ◽

Real World Data ◽

Study Heterogeneity ◽

Randomised Controlled

Abstract Background Use of real world data (RWD) from non-randomised studies (e.g. single-arm studies) is increasingly being explored to overcome issues associated with data from randomised controlled trials (RCTs). We aimed to compare methods for pairwise meta-analysis of RCTs and single-arm studies using aggregate data, via a simulation study and application to an illustrative example. Methods We considered contrast-based methods proposed by Begg & Pilote (1991) and arm-based methods by Zhang et al (2019). We performed a simulation study with scenarios varying (i) the proportion of RCTs and single-arm studies in the synthesis (ii) the magnitude of bias, and (iii) between-study heterogeneity. We also applied methods to data from a published health technology assessment (HTA), including three RCTs and 11 single-arm studies. Results Our simulation study showed that the hierarchical power and commensurate prior methods by Zhang et al provided a consistent reduction in uncertainty, whilst maintaining over-coverage and small error in scenarios where there was limited RCT data, bias and differences in between-study heterogeneity between the two sets of data. The contrast-based methods provided a reduction in uncertainty, but performed worse in terms of coverage and error, unless there was no marked difference in heterogeneity between the two sets of data. Conclusions The hierarchical power and commensurate prior methods provide the most robust approach to synthesising aggregate data from RCTs and single-arm studies, balancing the need to account for bias and differences in between-study heterogeneity, whilst reducing uncertainty in estimates. This work was restricted to considering a pairwise meta-analysis using aggregate data.

Download Full-text

The combination of a peginterferon plus ribavirin appears to be as effective in the 'real world' as in randomised, controlled trials

Inpharma Weekly ◽

10.2165/00128413-200816410-00027 ◽

2008 ◽

Vol &NA; (1641) ◽

pp. 15

Author(s):

&NA;

Keyword(s):

Real World ◽

Randomised Controlled Trials ◽

Controlled Trials ◽

The Real ◽

Randomised Controlled

Download Full-text

Protocol for data extraction: how real-world data have been used in the National Institute for Health and Care Excellence appraisals of cancer therapy

BMJ Open ◽

10.1136/bmjopen-2021-055985 ◽

2022 ◽

Vol 12 (1) ◽

pp. e055985

Author(s):

Jiyeon Kang ◽

John Cairns

Keyword(s):

Real World ◽

Data Extraction ◽

Systematic Research ◽

London School ◽

Real World Data ◽

World Data ◽

Data Extraction Tool ◽

Potential Benefits ◽

Critical Components ◽

Randomised Controlled

IntroductionDue to the limitations of relying on randomised controlled trials, the potential benefits of real-world data (RWD) in enriching evidence for health technology assessment (HTA) are highlighted. Despite increased interest in RWD, there is limited systematic research investigating how RWD have been used in HTA. The main purpose of this protocol is to extract relevant data from National Institute for Health and Care Excellence (NICE) appraisals in a transparent and reproducible manner in order to determine how NICE has incorporated a broader range of evidence in the appraisal of oncology medicines.Methods and analysisThe appraisals issued between January 2011 and May 2021 are included following inclusion criteria. The data extraction tool newly developed for this research includes the critical components of economic evaluation. The information is extracted from identified appraisals in accordance with extraction rules. The data extraction tool will be validated by a second researcher independently. The extracted data will be analysed quantitatively to investigate to what extent RWD have been used in appraisals. This is the first protocol to enable data to be extracted comprehensively and systematically in order to review the use of RWD.Ethics and disseminationThis study is approved by the Ethics Committee of the London School of Hygiene and Tropical Medicine on 14 November 2019 (17315). Results will be published in peer-reviewed journals.

Download Full-text

The Evolution of Clinical Trials in Oncology: Randomised Controlled Trials to Real World Studies

Annals of Oncology ◽

10.1093/annonc/mdu317.4 ◽

2014 ◽

Vol 25 ◽

pp. iv41

Author(s):

G.H. Lyman

Keyword(s):

Clinical Trials ◽

Real World ◽

Randomised Controlled Trials ◽

Controlled Trials ◽

Randomised Controlled

Download Full-text

Real-world research and its importance in respiratory medicine

Breathe ◽

10.1183/20734735.015414 ◽

2015 ◽

Vol 11 (1) ◽

pp. 26-38 ◽

Cited By ~ 42

Author(s):

David Price ◽

Guy Brusselle ◽

Nicolas Roche ◽

Daryl Freeman ◽

Alison Chisholm

Keyword(s):

Clinical Practice ◽

Treatment Outcomes ◽

Real World ◽

Randomised Controlled Trials ◽

Real Life ◽

Controlled Trials ◽

List Type ◽

Pragmatic Clinical Trials ◽

Randomised Controlled ◽

Meta Analyses

Educational AimsTo improve understanding of: The relative benefits and limitations of evidence derived from different study designs and the role that real-life asthma studies can play in addressing limitations in the classical randomised controlled trial (cRCT) evidence base.The importance of guideline recommendations being modified to fit the populations studied and the model of care provided in their reference studies.Key pointsClassical randomised controlled trials (cRCTs) show results from a narrow patient group with a constrained ecology of care.Patients with “real-life” co-morbidities and lifestyle factors receiving usual care often have different responses to medication which will not be captured by cRCTs if they are excluded by strict selection criteria.Meta-analyses, used to direct guidelines, contain an inherent meta-bias based on patient selection and artificial patient care.Guideline recommendations should clarify where they related to cRCT ideals (in terms of patient populations, medical resources and care received) and could be enhanced through inclusion of evidence from studies designed to better model the populations and care approaches present in routine care.SummaryClinical practice requires a complex interplay between experience and training, research, guidelines and judgement, and must not only draw on data from traditional or classical randomised controlled trials (cRCTs), but also from pragmatically designed studies that better reflect real-life clinical practice. To minimise extraneous variables and to optimise their internal validity, cRCTs exclude patients, clinical characteristics and variations in care that could potentially confound outcomes. The result is that respiratory cRCTs often enrol a small, non-representative subset of patients and overlook the important interplay and interactions between patients and the real world, which can effect treatment outcomes.Evidence from real-life studies (e.g. naturalistic or pragmatic clinical trials and observational studies encompassing healthcare database studies and cohort studies) can be combined with cRCT evidence to provide a fuller picture of intervention effectiveness and realistic treatment outcomes, and can provide useful insights into alternative management approaches in more challenging asthma patients. The Respiratory Effectiveness Group (REG), in collaboration with the European Academy of Allergy and Clinical Immunology (EAACI) and the European Respiratory Society (ERS), is developing quality appraisal tools and methods for integrating different sources of evidence. A REG/EAACI taskforce aims to help support future guideline developers to avoid a one-size-fits-all approach to recommendations and to tailor the conclusions of their meta-analyses to the populations under consideration.

Download Full-text