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Real-world evidence (RWE) is an emerging scientific discipline which is being increasingly utilised for decision making on prescription only medicines. However, there has been little focus to date on the application of RWE within the non-prescription sector. This paper reviews the existing and potential applications of RWE for non-prescription medicines, using the non-prescription medicine life-cycle as a framework for discussion. Relevant sources of real-world data (RWD) are reviewed and compared with those available for prescribed medicines. Existing life-cycle data gaps are identified where RWE is required or where use of RWE can complement data from randomised controlled trials (RCTs). Published RWE examples relating to non-prescription medicines are summarised, and potential relevant future sources of RWD discussed. Challenges and limitations to the use of RWE on non-prescription medicines are discussed, and recommendations made to promote optimal and appropriate use of RWE in this sector. Overall, RWE currently plays a key role in specific phases of the non-prescription medicine life-cycle, including reclassification and post-marketing safety surveillance. The increasing availability of patient-generated health data (PGHD) is likely to further increase the utilisation of RWE to aid decision making on non-prescription medicines.

Epidemiology and pharmacoepidemiology frequently employ Real-World Data (RWD) from healthcare teams to inform research. These data sources usually include signs, symptoms, tests, and treatments, but may lack important information such as the patient's diet or adherence or quality of life. By harnessing digital tools a new fount of evidence, Patient (or Citizen/Person) Generated Health Data (PGHD), is becoming more readily available. This review focusses on the advantages and considerations in using PGHD for pharmacoepidemiological research. New and corroborative types of data can be collected directly from patients using digital devices, both passively and actively. Practical issues such as patient engagement, data linking, validation, and analysis are among important considerations in the use of PGHD. In our ever increasingly patient-centric world, PGHD incorporated into more traditional Real-Word data sources offers innovative opportunities to expand our understanding of the complex factors involved in health and the safety and effectiveness of disease treatments. Pharmacoepidemiologists have a unique role in realizing the potential of PGHD by ensuring that robust methodology, governance, and analytical techniques underpin its use to generate meaningful research results.

The Fractal Bubble model has been proposed as a viable cosmology that does not require dark energy to account for cosmic acceleration, but rather attributes its observational signature to the formation of structure. In this paper it is demonstrated that, in contrast to previous findings, this model is not a good fit to cosmological supernovae data; there is significant tension in the best fit parameters obtained from different samples, whereas LCDM is able to fit all datasets consistently. Furthermore, the concordance between galaxy clustering scales and data from the cosmic microwave background is not achieved with the most recent supernova compilations. The validity of the FB formalism as a sound cosmological model is further challenged as it is shown that previous studies of this model achieve concordance by requiring a value for the present day Hubble constant that is derived from supernovae data containing an arbitrary distance normalisation., Comment: 6 pages, 3 figures, revised version published in MNRAS letters

We present the first study of early dark energy cosmologies using N-body simulations to investigate the formation of non-linear structure. In contrast to expectations from semi-analytic approaches, we find that early dark energy does not imprint a unique signature on the statistics of non-linear structures. Investigating the non-linear power spectra and halo mass functions, we show that universal mass functions hold for early dark energy, making its presence difficult to distinguish from $\Lambda$CDM. Since early dark energy biases the baryon acoustic oscillation scale, the lack of discriminating power is problematic., Comment: 11 pages, 19 figures. Minor changes to match version accepted to MNRAS

A straight-forward interpretation of standard Friedmann-Lemaitre-Robertson-Walker (FLRW) cosmologies is that objects move apart due to the expansion of space, and that sufficiently distant galaxies must be receding at velocities exceeding the speed of light. Recently, however, it has been suggested that a simple transformation into conformal coordinates can remove superluminal recession velocities, and hence the concept of the expansion of space should be abandoned. This work demonstrates that such conformal transformations do not eliminate superluminal recession velocities for open or flat matter-only FRLW cosmologies, and all possess superluminal expansion. Hence, the attack on the concept of the expansion of space based on this is poorly founded. This work concludes by emphasizing that the expansion of space is perfectly valid in the general relativistic framework, however, asking the question of whether space really expands is a futile exercise., Comment: 5 pages, accepted for publication in MNRAS Letters

For dynamical dark energy cosmologies we carry out a series of N-body gravitational simulations, achieving percent level accuracy in the relative mass power spectra at any redshift. Such accuracy in the power spectrum is necessary for next generation cosmological mass probes. Our matching procedure reproduces the CMB distance to last scattering and delivers subpercent level power spectra at z=0 and z~3. We discuss the physical implications for probing dark energy with surveys of large scale structure.

While it remains the staple of virtually all cosmological teaching, the concept of expanding space in explaining the increasing separation of galaxies has recently come under fire as a dangerous idea whose application leads to the development of confusion and the establishment of misconceptions. In this paper, we develop a notion of expanding space that is completely valid as a framework for the description of the evolution of the universe and whose application allows an intuitive understanding of the influence of universal expansion. We also demonstrate how arguments against the concept in general have failed thus far, as they imbue expanding space with physical properties not consistent with the expectations of general relativity., 8 pages, accepted for publication in PASA

The concept of expanding space has come under fire recently as being inadequate and even misleading in describing the motion of test particles in the universe. Previous investigations have suffered from a number of shortcomings, which we seek to correct. We study the motion of test particles in the universe in detail, solving the geodesic equations of General Relativity for a number of cosmological models. In particular, we use analytic methods to examine whether particles removed from the Hubble flow asymptotically rejoin the Hubble flow, a topic that has caused confusion because of differing definitions and invalid reasoning. We conclude that particles in eternally expanding but otherwise arbitrary universes do not in general rejoin the Hubble flow., Accepted for publication in MNRAS

We demonstrate that the principle of maximum relative entropy (ME), used judiciously, can ease the specification of priors in model selection problems. The resulting effect is that models that make sharp predictions are disfavoured, weakening the usual Bayesian "Occam's Razor". This is illustrated with a simple example involving what Jaynes called a "sure thing" hypothesis. Jaynes' resolution of the situation involved introducing a large number of alternative "sure thing" hypotheses that were possible before we observed the data. However, in more complex situations, it may not be possible to explicitly enumerate large numbers of alternatives. The entropic priors formalism produces the desired result without modifying the hypothesis space or requiring explicit enumeration of alternatives; all that is required is a good model for the prior predictive distribution for the data. This idea is illustrated with a simple rigged-lottery example, and we outline how this idea may help to resolve a recent debate amongst cosmologists: is dark energy a cosmological constant, or has it evolved with time in some way? And how shall we decide, when the data are in?, Comment: Presented at MaxEnt 2009, the 29th International Workshop on Bayesian Inference and Maximum Entropy Methods in Science and Engineering (July 5-10, 2009, Oxford, Mississippi, USA)

We present a matching procedure for rapidly calculating the non-linear mass power spectrum in dynamical dark energy cosmologies to percent level accuracy in the range of scales between 0.1 < k < 3. This procedure is verified by large N-body simulations and is valid at any redshift for cosmologies consistent with current observations. Such accuracy in the power spectrum is necessary for next generation cosmological mass probes. Our matching procedure reproduces the CMB distance to last scattering and delivers sub-percent level accuracy in the matter power spectra at z = 0 and z ≈ 3. We discuss the physical implications for probing dark energy with surveys of large scale structure.

While modern cosmology, founded in the language of general relativity, is almost a century old, the meaning of the expansion of space is still being debated. In this paper, the question of radar ranging in an expanding universe is examined, focusing upon light travel times during the ranging; it has recently been claimed that this proves that space physically expands. We generalize the problem into considering the return journey of an accelerating rocketeer, showing that while this agrees with expectations of special relativity for an empty universe, distinct differences occur when the universe contains matter. We conclude that this does not require the expansion of space to be a physical phenomenon, rather that we cannot neglect the influence of matter, seen through the laws of general relativity, when considering motions on cosmic scales., Comment: 6 Pages. To appear in MNRAS

We examine the linear density contrast at collapse time, $\delta_c$ for large-scale structure in dynamical dark energy cosmologies, including models with early dark energy. Contrary to previous results, we find that as long as dark energy is homogeneous on small scales, $\delta_c$ is insensitive to dark energy properties for parameter values fitting current data, including the case of early dark energy. This is significant since using the correct $\delta_c$ is crucial for accurate Press-Schechter prediction of the halo mass function. Previous results have found an apparent failing of the extended Press-Schechter approach (Sheth-Tormen) for early dark energy. Our calculations demonstrate that with the correct $\delta_c$ the accuracy of this approach is restored. We discuss the significance of this result for the halo mass function and examine what dark energy physics would be needed to cause significant change in $\delta_c$, and the observational signatures this would leave., Comment: 5 pages, 2 figures. Accepted for MNRAS Letters

This study used a finite helical axes representation to derive the axis of rotation of the human knee in the frontal plane for the neutral flexion/extension posture during resting and no load-bearing conditions. The three-dimensional finite helical axis pathway of the tibia relative to the femur was computed by passively adducting/abducting the lower limb via a servomotor system. Knee joint movements as a result of the positional perturbations were captured with an active marker kinematic tracking system. Contrary to traditional assumptions used in studies conducted under a similar experimental paradigm, our results indicated that the knee joint center, defined as the intercept point between the finite helical axis and the mid-coronal plane of the distal femur, was located within the femoral notch for a wide range of abduction and adduction angles (6° abduction to 6° adduction angles). Our data also indicated that at the neutral posture of the knee, the helical axes directions change as a function of the abduction/adduction perturbation angle. These findings are not only essential to error minimization during joint moment calculations, but can also facilitate new biomechanical interpretations of, for example, the functional role of the quadriceps and patellofemoral joint mechanics to overall knee stability in the medial–lateral direction. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res

Observational evidence indicating that the expansion of the universe is accelerating has surprised cosmologists in recent years. Cosmological models have sought to explain this acceleration by incorporating `dark energy', of which the traditional cosmological constant is just one possible candidate. Several cosmological models involving an evolving equation of state of the dark energy have been proposed, as well as possible energy exchange to other components, such as dark matter. This paper summarises the forms of the most prominent models and discusses their implications for cosmology and astrophysics. Finally, this paper examines the current and future observational constraints on the nature of dark energy., Comment: 11 pages, 11 figures, to appear in Proceedings of the Astronomical Society of Australia