Tackling Challenging Data Integrity Topics in 2020: Update on Good Clinical Practice Perspectives from the US FDA and MHRA UK.

With the globalization of clinical trials, regulators have increased collaboration to evaluate the adequacy of clinical trial conduct and to optimize regulatory oversight. The 2020 joint Good Clinical Practice (GCP) symposium of the US Food and Drug Administration and the UK Medicines and Healthcare products Regulatory Agency provided the agencies' perspectives on the challenges in ensuring data quality in novel clinical trial designs and the importance of the management and documentation of protocol deviations, sponsor oversight of clinical trials, and use of electronic source data, including electronic health records. This paper summarizes considerations of both agencies on these topics, along with case examples. This paper touches upon considerations when using real-world data to support regulatory decisions. It also discusses the impact of the coronavirus disease 2019 (COVID-19) pandemic on clinical trial conduct and underscores the importance of well-designed, resilient, and adaptable systems for GCP compliance and data integrity.

Clinical Integration of a Highly Accurate Polymerase Chain Reaction Point-of-Care Test Can Inform Immediate Treatment Decisions for Chlamydia, Gonorrhea, and Trichomonas.

BACKGROUND: Accurate same-day sexually transmitted infection (STI) diagnostic testing is generally unavailable, leading to syndromic management with high rates of overtreatment and undertreatment. We analyzed the ease of integration of the Visby STI Panel into clinical practice, studied acceptance by patients and clinic personnel, and assessed the potential to inform accurate treatment decisions. METHODS: In a cross-sectional single-visit study of 55 women aged 18 to 56 years, women self-collected vaginal swab samples that were analyzed using the Visby STI Panel for Chlamydia trachomatis, Neisseria gonorrhoeae (NG), and Trichomonas vaginalis (TV). Results were compared with standard-of-care clinic results from send-out laboratory polymerase chain reaction tests. Surveys assessed patient and device operator experiences with the Visby STI Panel and clinicians' perceived need for and acceptance of the device. Time parameters were measured to evaluate the impact on clinical workflow, and syndromic treatment decisions were compared with anticipated treatment based on the Visby STI Panel results. RESULTS: Patients strongly agreed that sample self-collection was easy, and operators reported the device easy to use. Clinicians valued the rapid return of results, and patients were comfortable waiting up to 30 minutes to receive them. In 13 of 15 cases, the Visby STI Panel correctly identified undertreated patients as infected and correctly identified all 33 incidences of overtreatment. CONCLUSIONS: Clinical adoption of the Visby STI Panel into primary care clinics and doctors' offices could reduce overtreatment and undertreatment of STIs. If integrated efficiently into the clinical workflow, the test would have minimal impact on staff time and visit duration for patients.

Realising the full potential of data-enabled trials in the UK: a call for action.

RATIONALE: Clinical trials are the gold standard for testing interventions. COVID-19 has further raised their public profile and emphasised the need to deliver better, faster, more efficient trials for patient benefit. Considerable overlap exists between data required for trials and data already collected routinely in electronic healthcare records (EHRs). Opportunities exist to use these in innovative ways to decrease duplication of effort and speed trial recruitment, conduct and follow-up. APPROACH: The National Institute of Health Research (NIHR), Health Data Research UK and Clinical Practice Research Datalink co-organised a national workshop to accelerate the agenda for 'data-enabled clinical trials'. Showcasing successful examples and imagining future possibilities, the plenary talks, panel discussions, group discussions and case studies covered: design/feasibility; recruitment; conduct/follow-up; collecting benefits/harms; and analysis/interpretation. REFLECTION: Some notable studies have successfully accessed and used EHR to identify potential recruits, support randomised trials, deliver interventions and supplement/replace trial-specific follow-up. Some outcome measures are already reliably collected; others, like safety, need detailed work to meet regulatory reporting requirements. There is a clear need for system interoperability and a 'route map' to identify and access the necessary datasets. Researchers running regulatory-facing trials must carefully consider how data quality and integrity would be assessed. An experience-sharing forum could stimulate wider adoption of EHR-based methods in trial design and execution. DISCUSSION: EHR offer opportunities to better plan clinical trials, assess patients and capture data more efficiently, reducing research waste and increasing focus on each trial's specific challenges. The short-term emphasis should be on facilitating patient recruitment and for postmarketing authorisation trials where research-relevant outcome measures are readily collectable. Sharing of case studies is encouraged. The workshop directly informed NIHR's funding call for ambitious data-enabled trials at scale. There is the opportunity for the UK to build upon existing data science capabilities to identify, recruit and monitor patients in trials at scale.

Comparative effects of two heat acclimation protocols consisting of high-intensity interval training in the heat on aerobic performance and thermoregulatory responses in exercising rats.

Acclimation resulting from low- to moderate-intensity physical exertion in the heat induces several thermoregulatory adaptations, including slower exercise-induced increases in core body temperature. However, few studies have investigated the thermoregulatory adaptations induced by high-intensity interval training (HIIT) protocols. Thus, the present study aimed to compare the adaptations in rats' thermoregulatory parameters and aerobic performance observed after two different heat acclimation regimens consisting of HIIT protocols performed in a hot environment. Twenty-three adult male Wistar rats were initially subjected to an incremental-speed exercise at 32°C until they were fatigued and then randomly assigned to one of the following three heat acclimation strategies: passive heat exposure without any exercise (untrained controls-UN; n = 7), HIIT performed at the maximal aerobic speed (HIIT100%; n = 8) and HIIT performed at a high but submaximal speed (HIIT85%; n = 8). Following the two weeks of interventions, the rats were again subjected to a fatiguing incremental exercise at 32°C, while their colonic temperature (TCOL) was recorded. The workload performed by the rats and their thermoregulatory efficiency were calculated. After the intervention period, rats subjected to both HIIT protocols attained greater workloads (HIIT100%: 313.7 ± 21.9 J vs. HIIT85%: 318.1 ± 32.6 J vs. UN: 250.8 ± 32.4 J; p < 0.01) and presented a lower ratio between the change in TCOL and the distance travelled (HIIT100%: 4.95 ± 0.42°C/km vs. HIIT85%: 4.33 ± 0.59°C/km vs. UN: 6.14 ± 1.03°C/km; p < 0.001) when compared to UN rats. The latter finding indicates better thermoregulatory efficiency in trained animals. No differences were observed between rats subjected to the two HIIT regimens. In conclusion, the two HIIT protocols induce greater thermoregulatory adaptations and performance improvements than passive heat exposure. These adaptations do not differ between the two training protocols investigated in the present study.

Análise da assimetria de força de preensão manual entre os sexos / Analysis of the asymmetry of hand gripping force between the sexes

É da natureza dos seres humanos apresentarem preferências na realização de tarefas do dia-a-dia. Esta preferência está associada à lateralidade. Um dos campos de estudo sobre a lateralidade é a assimetria lateral, que está presente tanto na dimensão da preferência quanto no desempenho. Objetivo: Este estudo teve como objetivo comparar a assimetria de força de preensão manual entre os sexos, e identificar se há associação entre assimetria de desempenho e assimetria de preferência. Método: A amostra foi composta por 50 estudantes universitários que realizaram teste de força de preensão manual máxima. Resultados: Os resultados indicaram que o os homens apresentaram valores absolutos maiores, maior índice de assimetria e menor consistência quando comparados às mulheres. Além disso, a mão preferida apresentou valores maiores de força em ambos os sexos. Conclusão: Em linhas gerais, sugere-se que fatores genéticos, sociais, culturais e sexo influenciam o comportamento motor dos indivíduos e, consequentemente, as assimetrias de desempenho.

It is of the nature of human beings to have preferences to performing daily tasks. This preference is associated with the laterality. One of the fields of the laterality study is lateral asymmetry, that is present in both preference and performance dimensions. Aim: This study aimed to compare manual grip strength asymmetry between genders and to identify if there is an association between asymmetry of performance and preference asymmetry. Method: The sample consisted of 50 university students who performed maximum manual grip strength tests. Results: The results indicated that the men had higher absolute values, higher Asymmetry Index and lower consistency when compared to the women. In addition, the preferred hand presented higher strength values in both sexes. Conclusion: In general, it is suggested that genetic, social, cultural and gender factors influence the motor behavior of the individuals and consequently the appearance of the lateral asymmetries.