Randomised clinical endpoint studies for trastuzumab biosimilars: a systematic review.

PURPOSE: Uptake of biosimilars depends on clinicians and patients having confidence in the evidential basis of marketing approval. The aim of this systematic review was to assess the evidential role of randomised clinical endpoint studies in the marketing approval of trastuzumab biosimilars. METHODS: We searched PubMed for any published reports of randomised studies associated with the five trastuzumab biosimilars approved by the EMA, as on 31 January 2019. We also searched ClinicalTrials.gov for any ongoing studies for other trastuzumab biosimilars. RESULTS: We identified eight published papers or abstracts for seven randomised clinical endpoint studies for five trastuzumab biosimilars approved by the EMA: four studies in the neoadjuvant setting and three in the first-line metastatic setting. Another six unpublished or ongoing studies for other trastuzumab biosimilars were identified via ClinicalTrials.gov. According to GRADE, and considered in isolation, the randomised studies would be categorised as low-quality evidence because of the use of surrogate endpoints and the small sample size. However, according to GRADE, the totality-of-evidence for each of the five approved trastuzumab biosimilars would be categorised as high quality in that further data would be unlikely to change the conclusion that each biosimilar was not different from Herceptin in any clinically important way. CONCLUSION: The pivotal data for each marketing approval was not the randomised clinical endpoint study, but the in vitro analytic characterisation. Regulatory confidence in in vitro analytic characterisation stems from years of experience with manufacturing changes for originator biological medicines. This emphasis on in vitro data, as the most sensitive way to detect clinically important differences, will be a new way of thinking for many oncologists.

Unfit for duty? Evaluation of 4 years of paramedic preemployment fitness screening test results.

BACKGROUND: Preemployment testing is utilized by many ambulance services. Surprisingly, there is limited published research on the efficacy of this testing in determining an employee's ability to complete the requirements of this physically demanding occupation. OBJECTIVES: The purpose of this study was to analyze the preemployment fitness test results from a 4-year cohort of paramedic students from an Australian university. To date, no published studies have reported on the fitness test scores for paramedic students or on whether overall test score is biased toward any particular test components. Similarly, no data have been presented on whether there are gender differences in scores for individual test components or overall test score. METHODS: Retrospective cohort study of de-identified data from 4 years of data from Paramedic Science students (n = 251) (mean age = 24.9 years). Data were recorded from the Queensland Ambulance Service (QAS) Health Related Fitness Test (HRFT), a preemployment fitness test used by an Australian state ambulance service. HRFT score is calculated out of a possible 100 points and is based on performance scores in nine component fitness tests. Raw test scores for each of these component tests are ranked on a 0-4 scale prior to these data being scaled and summed to generate the overall HRFT score. An overall score >24.99 is awarded a "Pass." Results. Five individuals failed to "Pass" the HRFT. Overall HRFT scores were influenced significantly by performance in the strength tests, with males also recording significantly (p < 0.005) higher scores in all of the strength tests than females. Similarly, approximately 40% of the female participants, compared to 6% of males, achieved an overall test "Pass" and yet gained a ranked score of 0 in at least three of the component tests. CONCLUSIONS: It was concluded that the scoring system did not exclude participants with poor fitness levels, as many participants recorded low scores in several test components yet still passed the test. We recommend that before redesigning the HRFT, studies should be first conducted on the occupational demands and physical standards required for this important profession.

Effectiveness of Home Gardening in Improving Food Security and Health in Chacraseca, Nicaragua: A Pilot Study.

We studied the usefulness of home gardening in improving food security and health. One hundred participants were randomized into the control and intervention group of which the intervention group received training in home gardening. Results showed that the percentage of participants with normal body mass index decreased from 24.4% to 20% in the control group whereas it remained unchanged in the intervention group. The number of participants in the very low food security category decreased from 66% (n=33) to 54% (n=27) in the intervention group whereas it increased from 68.8% (n=33) to 70.8% (n=34) in the control group. Results from the present study may be used to guide policymakers in designing or modifying home gardening interventions.

Effectiveness of Home Gardening in Improving Food Security and Health in Chacraseca, Nicaragua: A Pilot Study.

We studied the usefulness of home gardening in improving food security and health. One hundred participants were randomized into the control and intervention group of which the intervention group received training in home gardening. Results showed that the percentage of participants with normal body mass index decreased from 24.4% to 20% in the control group whereas it remained unchanged in the intervention group. The number of participants in the very low food security category decreased from 66% (n=33) to 54% (n=27) in the intervention group whereas it increased from 68.8% (n=33) to 70.8% (n=34) in the control group. Results from the present study may be used to guide policymakers in designing or modifying home gardening interventions.

Controlling stiffness in nanostructured hydrogels produced by enzymatic dephosphorylation.

In the present paper, we report on enzyme-initiated self-assembly of Fmoc (fluoren-9-ylmethoxycarbonyl)-tyrosine hydrogels by enzymatic dephosphorylation under physiological conditions and provide evidence for the ability to control the modulus. Upon enzyme action, a self-assembling network of interconnecting fibres is formed, observed by cryo-SEM (scanning electron microscopy) and TEM (transmission electron microscopy). The concentration of alkaline phosphatase added to the Fmoc-tyrosine phosphate ester precursor solution had a direct effect on the gelation time, mechanical properties and molecular arrangements as determined through oscillatory rheology, fluorescence spectroscopy and CD spectroscopy. This highly tuneable cost-effective gel system may have applications in three-dimensional cell culture.