Technology-Enabled Clinical Trials: Transforming Medical Evidence Generation.

The complexity and costs associated with traditional randomized, controlled trials have increased exponentially over time, and now threaten to stifle the development of new drugs and devices. Nevertheless, the growing use of electronic health records, mobile applications, and wearable devices offers significant promise for transforming clinical trials, making them more pragmatic and efficient. However, many challenges must be overcome before these innovations can be implemented routinely in randomized, controlled trial operations. In October of 2018, a diverse stakeholder group convened in Washington, DC, to examine how electronic health record, mobile, and wearable technologies could be applied to clinical trials. The group specifically examined how these technologies might streamline the execution of clinical trial components, delineated innovative trial designs facilitated by technological developments, identified barriers to implementation, and determined the optimal frameworks needed for regulatory oversight. The group concluded that the application of novel technologies to clinical trials provided enormous potential, yet these changes needed to be iterative and facilitated by continuous learning and pilot studies.

Hypothyroidism associated with therapy for multi-drug-resistant tuberculosis in Australia.

BACKGROUND: Reports from resource-poor countries have associated thionamide- and para-aminosalicylate sodium (PAS)-based treatment of multi-drug-resistant tuberculosis (MDR-TB) with the development of hypothyroidism. AIM: To identify predictors and assess the cumulative proportions of hypothyroidism in patients treated for MDR-TB with these agents in Australia. METHODS: Retrospective multicentre study of MDR-TB patients from five academic centres covering tuberculosis (TB) services in Victoria, Australia. Patients were identified using each centre's pharmacy department and cross checked with the Victorian Tuberculosis Program. Hypothyroidism was categorised as subclinical if the thyroid-stimulating hormone was elevated and as overt if free thyroxine (fT4) was additionally reduced on two separate occasions. Our main outcome measured was the cumulative proportion of hypothyroidism (at 5 years from treatment initiation). RESULTS: Of the 29 cases available for analysis, the cumulative proportion of hypothyroidism at 5 years was 37% (95% confidence interval (CI): 0-57.8%). Eight of the nine affected cases developed hypothyroidism within the first 12 months of treatment. Hypothyroidism was marginally (P = 0.06) associated with higher prothionamide/PAS dosing and was reversible with cessation of the anti-tuberculosis medication. CONCLUSIONS: Prothionamide/PAS treatment-associated hypothyroidism is common in MDR-TB patients in Australia, emphasising the importance of regular thyroid function monitoring during this treatment. Thyroid hormone replacement, if initiated, may not need to be continued after MDR-TB treatment is completed.

Impact of secondary health conditions on social role participation for a long-term physical disability cohort.

For people living with long-term physical disability (LTPD) social participation may involve managing physical impairments and secondary health conditions (SHCs) that are not due to the pathophysiology of the LTPD diagnosis itself. Prior research found a negative relationship between SHCs and participation in social roles in people with spinal cord injury (SCI). We expand on this research by investigating the influence of SHCs on participation in social roles for people with one of four LTPDs, controlling for co-variates. We (1) evaluated the associations between SHCs and participation in social roles; and (2) determined whether SHCs on individuals' ability to participate in social roles varies by type of diagnosis in those aging with either SCI, muscular sclerosis, muscular dystrophy, or post-polio syndrome. Cross-sectional, secondary data analysis from a return-by-mail survey. N = 1,573. Data were analyzed with multiple linear regressions (hypothesis 1), and then three moderated regressions (hypothesis 2). After controlling for demographics, SHCs were associated with lower ability to participate in social roles and accounted for 48% of the variance (all p's <.001). The relationship between depression and social role participation was moderated by diagnosis, such that depression was more negatively associated with social participation among individuals with SCI (p = .020). Thus, SHC negatively impact participation in social roles.

The role of machine learning in clinical research: transforming the future of evidence generation.

BACKGROUND: Interest in the application of machine learning (ML) to the design, conduct, and analysis of clinical trials has grown, but the evidence base for such applications has not been surveyed. This manuscript reviews the proceedings of a multi-stakeholder conference to discuss the current and future state of ML for clinical research. Key areas of clinical trial methodology in which ML holds particular promise and priority areas for further investigation are presented alongside a narrative review of evidence supporting the use of ML across the clinical trial spectrum. RESULTS: Conference attendees included stakeholders, such as biomedical and ML researchers, representatives from the US Food and Drug Administration (FDA), artificial intelligence technology and data analytics companies, non-profit organizations, patient advocacy groups, and pharmaceutical companies. ML contributions to clinical research were highlighted in the pre-trial phase, cohort selection and participant management, and data collection and analysis. A particular focus was paid to the operational and philosophical barriers to ML in clinical research. Peer-reviewed evidence was noted to be lacking in several areas. CONCLUSIONS: ML holds great promise for improving the efficiency and quality of clinical research, but substantial barriers remain, the surmounting of which will require addressing significant gaps in evidence.

Identification of targets for improving access to care in persons with long term physical disabilities.

BACKGROUND: People with long-term physical disability (LTPD) continue to experience difficulties in accessing health care despite the focus of highlighting disparities in the last two decades. OBJECTIVES: To describe health care utilization, accommodations and barriers experienced while accessing health care, and reasons why individuals delay or skip health care among people with LTPD. METHODS: The current study was a part of a larger longitudinal survey administered to individuals with physical disability associated with one of four long-term conditions (MS; SCI; PPS; MD). Measures included demographics, health care utilization, barriers to health care, and reasons for delaying or skipping medical care from the sixth wave of data from 2015 to 2016. RESULTS: Roughly 90% of all participants (N = 1159) saw at least one medical provider within 12 months. The most encountered barrier participants reported experiencing within that time was an office that did not have a safe transfer device to move them to an exam table (69%). Participants' physical function, quality of life, status of living with a spouse, diagnostic condition, and sex (male) were significantly associated with endorsing a barrier in accessing health care. The inability to afford out of pocket expenses was the highest reported reason for delaying health care. CONCLUSIONS: People with LTPD access a variety of health care, including rehabilitation services, and continue to experience barriers when doing so. While understanding barriers individuals experience when accessing health care is important, it is equally important to document the type of care they delay or skip due to barriers.

Regional medical campuses: a new classification system.

There is burgeoning belief that regional medical campuses (RMCs) are a significant part of the narrative about medical education and the health care workforce in the United States and Canada. Although RMCs are not new, in the recent years of medical education enrollment expansion, they have seen their numbers increase. Class expansion explains the rapid growth of RMCs in the past 10 years, but it does not adequately describe their function. Often, RMCs have missions that differ from their main campus, especially in the areas of rural and community medicine. The absence of an easy-to-use classification system has led to a lack of current research about RMCs as evidenced by the small number of articles in the current literature. The authors describe the process of the Group on Regional Medical Campuses used to develop attributes of a campus separate from the main campus that constitute a "classification" of a campus as an RMC. The system is broken into four models-basic science, clinical, longitudinal, and combined-and is linked to Liaison Committee on Medical Education standards. It is applicable to all schools and can be applied by any medical school dean or medical education researcher. The classification system paves the way for stakeholders to agree on a denominator of RMCs and conduct future research about their impact on medical education.

Aromatase inhibitors for PCOS: a systematic review and meta-analysis.

BACKGROUND: The effectiveness of aromatase inhibitors (AIs) in the treatment of anovulatory polycystic ovary syndrome (PCOS) remains unclear. The objective was to determine whether AIs are effective in improving fertility outcomes in women with PCOS. METHODS: Databases were searched until July 2011. Inclusion criteria were women with PCOS, who are infertile, receiving any type, dose and frequency of AI compared with placebo, no other treatment or other infertility treatment. Outcomes were rates of: ovulation, pregnancy, live birth, multiple pregnancies, miscarriage and adverse events, as well as quality of life and cost effectiveness. Data were extracted and risk of bias was assessed. A random-effects model was used for the meta-analyses, using odds ratios (ORs) and rate ratios (RRs). RESULTS: The search returned 4981 articles, 78 articles addressed AIs and 13 randomized controlled trials (RCTs) met the inclusion criteria. No RCTs compared AIs versus placebo or no treatment, in therapy naïve women with PCOS. Meta-analyses of six RCTs comparing letrozole with clompihene citrate (CC) demonstrated that letrozole improved the ovulation rate per patient [OR 2.90 (95% confidence interval (CI) 1.72, 4.88), I(2) = 0%, P < 0.0001]; however, there was no statistical difference for the ovulation rate per cycle or the pregnancy, live birth, multiple pregnancy or miscarriage rates. Letrozole also did not improve pregnancy or live birth rates compared with placebo or with CC plus metoformin in women with CC-resistant PCOS. Results of comparisons of letrozole and anastrozole in women with CC-resistant PCOS were conflicting in terms of ovulation and pregnancy rates. CONCLUSIONS: In the absence of supportive high-quality evidence, AIs should not be recommended as the first-line pharmacological therapy for infertility in women with PCOS, and further research is needed.