Current recommendations/practices for anonymising data from clinical trials in order to make it available for sharing:A scoping review

BACKGROUND/AIMS: There are increasing pressures for anonymised datasets from clinical trials to be shared across the scientific community, and differing recommendations exist on how to perform anonymisation prior to sharing. We aimed to systematically identify, describe and synthesise existing recommendations for anonymising clinical trial datasets to prepare for data sharing. METHODS: We systematically searched MEDLINE(®), EMBASE and Web of Science from inception to 8 February 2021. We also searched other resources to ensure the comprehensiveness of our search. Any publication reporting recommendations on anonymisation to enable data sharing from clinical trials was included. Two reviewers independently screened titles, abstracts and full text for eligibility. One reviewer extracted data from included papers using thematic synthesis, which then was sense-checked by a second reviewer. Results were summarised by narrative analysis. RESULTS: Fifty-nine articles (from 43 studies) were eligible for inclusion. Three distinct themes are emerging: anonymisation, de-identification and pseudonymisation. The most commonly used anonymisation techniques are: removal of direct patient identifiers; and careful evaluation and modification of indirect identifiers to minimise the risk of identification. Anonymised datasets joined with controlled access was the preferred method for data sharing. CONCLUSIONS: There is no single standardised set of recommendations on how to anonymise clinical trial datasets for sharing. However, this systematic review shows a developing consensus on techniques used to achieve anonymisation. Researchers in clinical trials still consider that anonymisation techniques by themselves are insufficient to protect patient privacy, and they need to be paired with controlled access

Water-Based 3D Inkjet Printing of an Oral Pharmaceutical Dosage Form

Inkjet printing is a form of additive manufacturing where liquid droplets are selectively deposited onto a substrate followed by solidification. The process provides significant potential advantages for producing solid oral dosage forms or tablets, including a reduction in the number of manufacturing steps as well as the ability to tailor a unique dosage regime to an individual patient. This study utilises solvent inkjet printing to print tablets through the use of a Fujifilm Dimatix printer. Using polyvinylpyrrolidone and thiamine hydrochloride (a model excipient and drug, respectively), a water-based ink formulation was developed to exhibit reliable and effective jetting properties. Tablets were printed on polyethylene terephthalate films where solvent evaporation in the ambient environment was the solidification mechanism. The tablets were shown to contain a drug loading commensurate with the composition of the ink, in its preferred polymorphic phase of a non-stoichiometric hydrate distributed homogenously. The printed tablets displayed rapid drug release. This paper illustrates solvent inkjet printing’s ability to print entire free-standing tablets without an edible substrate being part of the tablet and the use of additional printing methods. Common problems with solvent-based inkjet printing, such as the use toxic solvents, are avoided. The strategy developed here for tablet manufacturing from a suitable ink is general and provides a framework for the formulation for any drug that is soluble in water

3D printing of tablets using inkjet with UV photoinitiation

Additive manufacturing (AM) offers significant potential benefits in the field of drug delivery and pharmaceutical/medical device manufacture. Of AM processes, 3D inkjet printing enables precise deposition of a formulation, whilst offering the potential for significant scale up or scale out as a manufacturing platform. This work hypothesizes that suitable solvent based ink formulations can be developed that allow the production of solid dosage forms that meet the standards required for pharmaceutical tablets, whilst offering a platform for flexible and personalised manufacture. We demonstrate this using piezo-activated inkjetting to 3D print ropinirole hydrochloride. The tablets produced consist of a cross-linked poly(ethylene glycol diacrylate) (PEGDA) hydrogel matrix containing the drug, photoinitiated in a low oxygen environment using an aqueous solution of Irgacure 2959. At a Ropinirole HCl loading of 0.41 mg, drug release from the tablet is shown to be Fickian. Raman and IR spectroscopy indicate a high degree of cross-linking and formation of an amorphous solid dispersion. This is the first publication of a UV inkjet 3D printed tablet. Consequently, this work opens the possibility for the translation of scalable, high precision and bespoke ink-jet based additive manufacturing to the pharmaceutical sector

multifunctional bioinstructive 3d architectures to modulate cellular behavior

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Targeted rehabilitation to improve outcome after total knee replacement (TRIO): study protocol for a randomised controlled trial

BackgroundApproximately 20% of patients are not satisfied with the outcome of total knee replacement, great volumes of which are carried out yearly. Physiotherapy is often provided by the NHS to address dysfunction following knee replacement; however the efficacy of this is unknown. Although clinically it is accepted that therapy is useful, provision of physiotherapy to all patients post-operatively does not enhance outcomes at one year. No study has previously assessed the effect of targeting therapy to individuals struggling to recover in the early post-operative phase.The aim of the TRIO study is to determine whether stratifying care by targeting physiotherapy to those individuals performing poorly following knee replacement is effective in improving the one year outcomes. We are also investigating whether the structure of the physiotherapy provision itself influences outcomes.Methods/DesignThe study is a multi-centre prospective randomised controlled trial (RCT) of patients undergoing primary total knee replacement, with treatment targeted at those deemed most susceptible to gain from it. Use of the national PROMS programme for pre-operative data collection allows us to screen all patients at initial post-operative clinical review, and recruit only those deemed to be recovering slowly.We aim to recruit 440 patients through various NHS orthopaedic centres who will undergo six weeks of physiotherapy. The intervention will be either ‘intensive’ involving both hospital and home-based functional exercise rehabilitation, or ‘standard of care’ consisting of home exercises. Patients will be randomised to either group using a web-based system. Both groups will receive pre and post-intervention physiotherapy review. Patients will be followed-up to one year post-operation. The primary outcome measure is the Oxford Knee Score. Secondary outcomes are patient satisfaction, functional ability, pain scores and cost-effectiveness

Troponin in Acute Chest Pain to Risk Stratify and Guide Effective Use of Computed Tomography Coronary Angiography (TARGET-CTCA): A Randomised Controlled Trial

BACKGROUND: The majority of patients with suspected acute coronary syndrome presenting to the emergency department will be discharged once myocardial infarction has been ruled out, although a proportion will have unrecognised coronary artery disease. In this setting, high-sensitivity cardiac troponin identifies those at increased risk of future cardiac events. In patients with intermediate cardiac troponin concentrations in whom myocardial infarction has been ruled out, this trial aims to investigate whether outpatient computed tomography coronary angiography (CTCA) reduces subsequent myocardial infarction or cardiac death. METHODS: TARGET-CTCA is a multicentre prospective randomised open label with blinded endpoint parallel group event driven trial. After myocardial infarction and clear alternative diagnoses have been ruled out, participants with intermediate cardiac troponin concentrations (5 ng/L to 99th centile upper reference limit) will be randomised 1:1 to outpatient CTCA plus standard of care or standard of care alone. The primary endpoint is myocardial infarction or cardiac death. Secondary endpoints include clinical, patient-centred, process and cost-effectiveness. Recruitment of 2270 patients will give 90% power with a two-sided P value of 0.05 to detect a 40% relative risk reduction in the primary endpoint. Follow-up will continue until 97 primary outcome events have been accrued in the standard care arm with an estimated median follow-up of 36 months. DISCUSSION: This randomised controlled trial will determine whether high-sensitivity cardiac troponin-guided CTCA can improve outcomes and reduce subsequent major adverse cardiac events in patients presenting to the emergency department who do not have myocardial infarction

Troponin in Acute chest pain to Risk stratify and Guide EffecTive use of Computed Tomography Coronary Angiography (TARGET-CTCA):A randomised controlled trial

Background: The majority of patients with suspected acute coronary syndrome presenting to the emergency department will be discharged once myocardial infarction has been ruled out, although a proportion will have unrecognised coronary artery disease. In this setting, high-sensitivity cardiac troponin identifies those at increased risk of future cardiac events. In patients with intermediate cardiac troponin concentrations in whom myocardial infarction has been ruled out, this trial aims to investigate whether outpatient computed tomography coronary angiography (CTCA) reduces subsequent myocardial infarction or cardiac death. Methods: TARGET-CTCA is a multicentre prospective randomised open label with blinded endpoint parallel group event driven trial. After myocardial infarction and clear alternative diagnoses have been ruled out, participants with intermediate cardiac troponin concentrations (5 ng/L to 99th centile upper reference limit) will be randomised 1:1 to outpatient CTCA plus standard of care or standard of care alone. The primary endpoint is myocardial infarction or cardiac death. Secondary endpoints include clinical, patient-centred, process and cost-effectiveness. Recruitment of 2270 patients will give 90% power with a two-sided P value of 0.05 to detect a 40% relative risk reduction in the primary endpoint. Follow-up will continue until 97 primary outcome events have been accrued in the standard care arm with an estimated median follow-up of 36 months. Discussion: This randomised controlled trial will determine whether high-sensitivity cardiac troponin-guided CTCA can improve outcomes and reduce subsequent major adverse cardiac events in patients presenting to the emergency department who do not have myocardial infarction. Trial registration: ClinicalTrials.gov Identifier: NCT03952351. Registered on May 16, 2019

A Tripropylene Glycol Diacrylate-based Polymeric Support Ink for Material Jetting

© 2017 Support structures and materials are indispensable components in many Additive Manufacturing (AM) systems in order to fabricate complex 3D structures. For inkjet-based AM techniques (known as Material Jetting), there is a paucity of studies on specific inks for fabricating such support structures. This limits the potential of fabricating complex 3D objects containing overhanging structures. In this paper, we investigate the use of Tripropylene Glycol Diacrylated (TPGDA) to prepare a thermally stable ink with reliable printability to produce removable support structures in an experimental Material Jetting system. The addition of TGME to the TPGDA was found to considerably reduce the modulus of the photocured structure from 575MPa down to 27MPa by forming micro-pores in the cured structure. The cured support structure was shown to be easily removed following the fabrication process. During TG-IR tests the T 5% temperature of the support structure was above 150°C whilst the majority of decomposition happened around 400°C. Specimens containing overhanging structures (gate-like structure, propeller structure) were successfully manufactured to highlight the viability of the ink as a support material