What is a pilot or feasibility study? A review of current practice and editorial policy

Background: In 2004, a review of pilot studies published in seven major medical journals during 2000-01 recommended that the statistical analysis of such studies should be either mainly descriptive or focus on sample size estimation, while results from hypothesis testing must be interpreted with caution. We revisited these journals to see whether the subsequent recommendations have changed the practice of reporting pilot studies. We also conducted a survey to identify the methodological components in registered research studies which are described as 'pilot' or 'feasibility' studies. We extended this survey to grant-awarding bodies and editors of medical journals to discover their policies regarding the function and reporting of pilot studies. Methods: Papers from 2007-08 in seven medical journals were screened to retrieve published pilot studies. Reports of registered and completed studies on the UK Clinical Research Network (UKCRN) Portfolio database were retrieved and scrutinized. Guidance on the conduct and reporting of pilot studies was retrieved from the websites of three grant giving bodies and seven journal editors were canvassed. Results: 54 pilot or feasibility studies published in 2007-8 were found, of which 26 (48%) were pilot studies of interventions and the remainder feasibility studies. The majority incorporated hypothesis-testing (81%), a control arm (69%) and a randomization procedure (62%). Most (81%) pointed towards the need for further research. Only 8 out of 90 pilot studies identified by the earlier review led to subsequent main studies. Twelve studies which were interventional pilot/feasibility studies and which included testing of some component of the research process were identified through the UKCRN Portfolio database. There was no clear distinction in use of the terms 'pilot' and 'feasibility'. Five journal editors replied to our entreaty. In general they were loathe to publish studies described as 'pilot'. Conclusion: Pilot studies are still poorly reported, with inappropriate emphasis on hypothesis-testing. Authors should be aware of the different requirements of pilot studies, feasibility studies and main studies and report them appropriately. Authors should be explicit as to the purpose of a pilot study. The definitions of feasibility and pilot studies vary and we make proposals here to clarify terminology

Are pilot trials useful for predicting randomisation and attrition rates in definitive studies: A review of publicly funded trials

BACKGROUND/AIMS: External pilot trials are recommended for testing the feasibility of main or confirmatory trials. However, there is little evidence that progress in external pilot trials actually predicts randomisation and attrition rates in the main trial. To assess the use of external pilot trials in trial design, we compared randomisation and attrition rates in publicly funded randomised controlled trials with rates in their pilots. METHODS: Randomised controlled trials for which there was an external pilot trial were identified from reports published between 2004 and 2013 in the Health Technology Assessment Journal. Data were extracted from published papers, protocols and reports. Bland-Altman plots and descriptive statistics were used to investigate the agreement of randomisation and attrition rates between the full and external pilot trials. RESULTS: Of 561 reports, 41 were randomised controlled trials with pilot trials and 16 met criteria for a pilot trial with sufficient data. Mean attrition and randomisation rates were 21.1% and 50.4%, respectively, in the pilot trials and 16.8% and 65.2% in the main. There was minimal bias in the pilot trial when predicting the main trial attrition and randomisation rate. However, the variation was large: the mean difference in the attrition rate between the pilot and main trial was -4.4% with limits of agreement of -37.1% to 28.2%. Limits of agreement for randomisation rates were -47.8% to 77.5%. CONCLUSION: Results from external pilot trials to estimate randomisation and attrition rates should be used with caution as comparison of the difference in the rates between pilots and their associated full trial demonstrates high variability. We suggest using internal pilot trials wherever appropriate

Supersymmetry in carbon nanotubes in a transverse magnetic field

Electron properties of Carbon nanotubes in a transverse magnetic field are studied using a model of a massless Dirac particle on a cylinder. The problem possesses supersymmetry which protects low energy states and ensures stability of the metallic behavior in arbitrarily large fields. In metallic tubes we find suppression of the Fermi velocity at half-filling and enhancement of the density of states. In semiconducting tubes the energy gap is suppressed. These features qualitatively persist (although to a smaller degree) in the presence of electron interactions. The possibilities of experimental observation of these effects are discussed.Comment: A new section on electron interaction effects added and explanation on roles of supersymmetry expanded. Revtex4, 6 EPS figure file

(1+1)-Dirac particle with position-dependent mass in complexified Lorentz scalar interactions: effectively PT-symmetric

The effect of the built-in supersymmetric quantum mechanical language on the spectrum of the (1+1)-Dirac equation, with position-dependent mass (PDM) and complexified Lorentz scalar interactions, is re-emphasized. The signature of the "quasi-parity" on the Dirac particles' spectra is also studied. A Dirac particle with PDM and complexified scalar interactions of the form S(z)=S(x-ib) (an inversely linear plus linear, leading to a PT-symmetric oscillator model), and S(x)=S_{r}(x)+iS_{i}(x) (a PT-symmetric Scarf II model) are considered. Moreover, a first-order intertwining differential operator and an $\eta$-weak-pseudo-Hermiticity generator are presented and a complexified PT-symmetric periodic-type model is used as an illustrative example.Comment: 11 pages, no figures, revise

Use of MRI in the diagnosis of fetal brain abnormalities in utero (MERIDIAN): a multicentre, prospective cohort study.

BACKGROUND: In-utero MRI (iuMRI) has shown promise as an adjunct to ultrasound but the comparative diagnostic performance has been poorly defined. We aimed to assess whether the diagnostic accuracy and confidence of the prenatal diagnosis of fetal brain abnormalities is improved with iuMRI and assess the clinical impact and patient acceptability of iuMRI. METHODS: We did a multicentre, prospective, cohort study in the UK, at 16 fetal medicine centres, of pregnant women aged 16 years or older whose fetus had a brain abnormality detected by ultrasound at a gestational age of 18 weeks or more, had no contraindications to iuMRI, and consented to enter the study. Women carrying a fetus suspected of having a brain anomaly on ultrasound had iuMRI done within 14 days of ultrasound. The findings were reviewed by two independent panels and used to estimate diagnostic accuracy and confidence by comparison with outcome diagnoses. Changes in diagnosis, prognosis, and clinical management brought about by iuMRI and patient acceptability were assessed. FINDINGS: Participants were recruited between July 29, 2011, and Aug 31, 2014. The cohort was subdivided by gestation into the 18 weeks to less than 24 weeks fetus cohort (n=369) and into the 24 weeks or older fetus cohort (n=201). Diagnostic accuracy was improved by 23% (95% CI 18-27) in the 18 weeks to less than 24 weeks group and 29% (23-36) in the 24 weeks and older group (p<0·0001 for both groups). The overall diagnostic accuracy was 68% for ultrasound and 93% for iuMRI (difference 25%, 95% CI 21-29). Dominant diagnoses were reported with high confidence on ultrasound in 465 (82%) of 570 cases compared with 544 (95%) of 570 cases on iuMRI. IuMRI provided additional diagnostic information in 387 (49%) of 783 cases, changed prognostic information in at least 157 (20%), and led to changes in clinical management in more than one in three cases. IuMRI also had high patient acceptability with at least 95% of women saying they would have an iuMRI study if a future pregnancy were complicated by a fetal brain abnormality. INTERPRETATION: iuMRI improves diagnostic accuracy and confidence for fetal brain anomalies and leads to management changes in a high proportion of cases. This finding, along with the high patient acceptability, leads us to propose that any fetus with a suspected brain abnormality on ultrasound should have iuMRI to better inform counselling and management decisions. FUNDING: National Institute for Health Research Health Technology Assessment programme

Further Evidence Suggestive of a Solar Influence on Nuclear Decay Rates

Recent analyses of nuclear decay data show evidence of variations suggestive of a solar influence. Analyses of datasets acquired at the Brookhaven National Laboratory (BNL) and at the Physikalisch-Technische Bundesanstalt (PTB) both show evidence of an annual periodicity and of periodicities with sidereal frequencies in the neighborhood of 12.25 year^{-1} (at a significance level that we have estimated to be 10^{-17}). It is notable that this implied rotation rate is lower than that attributed to the solar radiative zone, suggestive of a slowly rotating solar core. This leads us to hypothesize that there may be an "inner tachocline" separating the core from the radiative zone, analogous to the "outer tachocline" that separates the radiative zone from the convection zone. The Rieger periodicity (which has a period of about 154 days, corresponding to a frequency of 2.37 year^{-1}) may be attributed to an r-mode oscillation with spherical-harmonic indices l=3, m=1, located in the outer tachocline. This suggests that we may test the hypothesis of a solar influence on nuclear decay rates by searching BNL and PTB data for evidence of a "Rieger-like" r-mode oscillation, with l=3, m=1, in the inner tachocline. The appropriate search band for such an oscillation is estimated to be 2.00-2.28 year^{-1}. We find, in both datasets, strong evidence of a periodicity at 2.11 year^{-1}. We estimate that the probability of obtaining these results by chance is 10^{-12}.Comment: 12 pages, 6 figures, v2 has a color corrected Fig 6, a corrected reference, and a corrected typ

Onset of magnetism in B2 transition metals aluminides

Ab initio calculation results for the electronic structure of disordered bcc Fe(x)Al(1-x) (0.4<x<0.75), Co(x)Al(1-x) and Ni(x)Al(1-x) (x=0.4; 0.5; 0.6) alloys near the 1:1 stoichiometry, as well as of the ordered B2 (FeAl, CoAl, NiAl) phases with point defects are presented. The calculations were performed using the coherent potential approximation within the Korringa-Kohn-Rostoker method (KKR-CPA) for the disordered case and the tight-binding linear muffin-tin orbital (TB-LMTO) method for the intermetallic compounds. We studied in particular the onset of magnetism in Fe-Al and Co-Al systems as a function of the defect structure. We found the appearance of large local magnetic moments associated with the transition metal (TM) antisite defect in FeAl and CoAl compounds, in agreement with the experimental findings. Moreover, we found that any vacancies on both sublattices enhance the magnetic moments via reducing the charge transfer to a TM atom. Disordered Fe-Al alloys are ferromagnetically ordered for the whole range of composition studied, whereas Co-Al becomes magnetic only for Co concentration >0.5.Comment: 11 pages with 9 embedded postscript figures, to be published in Phys.Rev.

AfrOBIS: a marine biogeographic information system for sub-Saharan Africa

AfrOBIS is one of 11 global nodes of the Ocean Biogeographic Information System (OBIS), a freely accessible network of databases collating marine data in support of the Census of Marine Life. Versatile graphic products, provided by OBIS, can be used to display the data. To date, AfrOBIS has loaded about3.2 million records of more than 23 000 species located mainly in the seas around southern Africa. This forms part of the 13.2 million records of more than 80 000 species currently stored in OBIS. Scouting for South African data has been successful, whereas locating records in other African countries has been much less so

Spectral and transport properties of doped Mott-Hubbard systems with incommensurate magnetic order

We present spectral and optical properties of the Hubbard model on a two-dimensional square lattice using a generalization of dynamical mean-field theory to magnetic states in finite dimension. The self-energy includes the effect of spin fluctuations and screening of the Coulomb interaction due to particle-particle scattering. At half-filling the quasiparticles reduce the width of the Mott-Hubbard `gap' and have dispersions and spectral weights that agree remarkably well with quantum Monte Carlo and exact diagonalization calculations. Away from half-filling we consider incommensurate magnetic order with a varying local spin direction, and derive the photoemission and optical spectra. The incommensurate magnetic order leads to a pseudogap which opens at the Fermi energy and coexists with a large Mott-Hubbard gap. The quasiparticle states survive in the doped systems, but their dispersion is modified with the doping and a rigid band picture does not apply. Spectral weight in the optical conductivity is transferred to lower energies and the Drude weight increases linearly with increasing doping. We show that incommensurate magnetic order leads also to mid-gap states in the optical spectra and to decreased scattering rates in the transport processes, in qualitative agreement with the experimental observations in doped systems. The gradual disappearence of the spiral magnetic order and the vanishing pseudogap with increasing temperature is found to be responsible for the linear resistivity. We discuss the possible reasons why these results may only partially explain the features observed in the optical spectra of high temperature superconductors.Comment: 22 pages, 18 figure

Spin-Charge Separation in the t−Jt-J Model: Magnetic and Transport Anomalies

A real spin-charge separation scheme is found based on a saddle-point state of the $t-J$ model. In the one-dimensional (1D) case, such a saddle-point reproduces the correct asymptotic correlations at the strong-coupling fixed-point of the model. In the two-dimensional (2D) case, the transverse gauge field confining spinon and holon is shown to be gapped at {\em finite doping} so that a spin-charge deconfinement is obtained for its first time in 2D. The gap in the gauge fluctuation disappears at half-filling limit, where a long-range antiferromagnetic order is recovered at zero temperature and spinons become confined. The most interesting features of spin dynamics and transport are exhibited at finite doping where exotic {\em residual} couplings between spin and charge degrees of freedom lead to systematic anomalies with regard to a Fermi-liquid system. In spin dynamics, a commensurate antiferromagnetic fluctuation with a small, doping-dependent energy scale is found, which is characterized in momentum space by a Gaussian peak at ($\pi/a$, $\pi/a$) with a doping-dependent width ($\propto \sqrt{\delta}$, $\delta$ is the doping concentration). This commensurate magnetic fluctuation contributes a non-Korringa behavior for the NMR spin-lattice relaxation rate. There also exits a characteristic temperature scale below which a pseudogap behavior appears in the spin dynamics. Furthermore, an incommensurate magnetic fluctuation is also obtained at a {\em finite} energy regime. In transport, a strong short-range phase interference leads to an effective holon Lagrangian which can give rise to a series of interesting phenomena including linear-$T$ resistivity and $T^2$ Hall-angle. We discuss the striking similarities of these theoretical features with those found in the high-$T_c$ cuprates and give aComment: 70 pages, RevTex, hard copies of 7 figures available upon request; minor revisions in the text and references have been made; To be published in July 1 issue of Phys. Rev. B52, (1995