Inverting the patient involvement paradigm: defining patient led research.

PLAIN ENGLISH SUMMARY: Patients usually understand their disease and lifestyle needs better than many medical professionals. They also have important ideas about what research would be most beneficial to their lives, especially on how to manage symptoms in a way that improves daily quality of life. In the UK, the National Institute for Health Research has recognised the value of patient insight, and now requires researchers with public funding to involve patients and the public throughout the research process. There are many opportunities for involvement, but these generally focus on improving study design to ensure the trial is acceptable to participants. Some programmes work towards setting research priorities as important to patients, public members, and medical experts, but due to the complexity and cost involved in running clinical trials, the majority of research originates with the pharmaceutical industry or academic institutions. There is a clear mismatch between research ideas that patients prioritise (quality of life), and those actually investigated (drug development).The Patient Led Research Hub (PLRH) is a new initiative hosted by the Cambridge Clinical Trials Unit. The PLRH supports research ideas as proposed by patient organisations, providing resources and expertise in research design and delivery. The PLRH aims to co-produce any technically feasible project, regardless of disease or symptom focus. The proposing patient group maintains ownership of the project with an active role in study management. This method of research has proven to produce credible research studies that are of direct relevance to patients. ABSTRACT: Patient and Public Involvement has become an indispensable and expected component of healthcare research in the United Kingdom, largely driven by the National Institute of Health Research and other research funders. Opportunities for patients to become involved in research abound, and many organisations now have dedicated 'public involvement' teams. However, its value is often questioned amidst criticism of tokenism and the recognition that a mismatch persists between patient priorities and funded research. Although patients are frequently consulted, evidence that their involvement influences the research agenda remains limited. We propose a novel model that allows patients and the public not only to propose research questions, but to design, initiate and deliver their own research with all the necessary support from research professionals. We demonstrate the feasibility and utility of this approach in reporting the establishment, experiences and progress of the Patient Led Research Hub. Using this resource, patient organisations are now able to initiate and conduct rigorous clinical research unfettered by the constraints of academic or economic agendas.

Randomised controlled trial of high versus ad libitum water intake in patients with autosomal dominant polycystic kidney disease: rationale and design of the DRINK feasibility trial.

INTRODUCTION: Vasopressin stimulates cyst growth in autosomal dominant polycystic kidney disease (ADPKD) leading to enlarged kidneys, hypertension and renal failure. Vasopressin receptor blockade slows disease progression. Physiological suppression of vasopressin secretion through high water (HW) intake could achieve a similar effect, necessitating a definitive large-scale trial of HW intake in ADPKD. The objective of the DRINK trial is to answer the key design and feasibility questions required to deliver a successful definitive water intake trial. METHODS AND ANALYSIS: We describe the design of a single-centre, open-label, prospective, randomised controlled trial. The "Determining feasibility of R andomisation to high vs. ad libitum water In take in Polycystic K idney Disease" (DRINK) trial aims to enrol 50 patients with ADPKD, over the age of 16 years with an estimated glomerular filtration rate (eGFR) ≥20 mL/min/1.73 m2. Participants will be randomised 1:1 to HW intake based on an individualised water intake prescription, or to ad libitum (AW) water intake. The HW group will aim for a dilute urine (urine osmolality ≤270 mOsm/kg) as a surrogate marker of vasopressin suppression, and those in the AW group will target more concentrated urine. Participants will have an 8-week treatment period, and will be seen at weeks 0, 2, 4 and 8, undergoing assessments of fluid status, renal function and serum and urine osmolalities. They will receive dietary advice, and self-monitor urine specific gravity and fluid intake. The trial employs smartphone technology to permit home monitoring and remote direct data capture. The primary feasibility end points are recruitment rate and separation between arms in measured urinary osmolality. Key secondary assessments include acceptability, adherence, health-related quality of life, acute effects of HW intake on measured (51Cr-EDTA) and eGFR and ADPKD-related pain. ETHICS AND DISSEMINATION: Ethical approval was awarded by the East of England Essex Research Ethics Committee (16/EE/0026). The results of DRINK will be submitted to peer-reviewed journals, and presented to patients via the PKD Charity. TRIAL REGISTRATION NUMBER: NCT02933268 and ISCRTN16794957.

Sex-related differences in the hemispheric laterality of slow cortical potentials during the preparation of visually guided movements.

Previous work suggests the presence of sex differences in the laterality of brain activity in the premotor-parietal network during the preparation of visually guided reaching movements. In the current study, electroencephalography was used to test the hypothesis that women would have higher amplitude potentials over frontal and parietal regions ipsilateral to arm movements, relative to men. Event-related slow cortical potentials (SCPs) were collected from 30 participants (15 men and 15 women) during the performance of two visually guided reaching conditions (eyes and arm moved to the same spatial location or moved in opposite directions). The results of the study demonstrate that the amplitudes of SCPs were significantly higher overlying frontal regions of the right hemisphere of women relative to men. These differences were present both during an instructed-delay period prior to receiving a go-signal to initiate movement and during the period just prior to movement initiation. The study also revealed an interaction of Sex and Condition in the parietal region during the pre-movement period. These results suggest that motor preparatory activity in men mainly occurs in the hemisphere contralateral to reaching but that preparatory activity in women is distributed relatively more bilaterally. However, the nature of these differences changes over the time course of the preparatory period and is partially dependent on the type of visuomotor mapping being performed.