This resource is a video abstract of a research paper created by Research Square on behalf of its authors. It provides a synopsis that's easy to understand, and can be used to introduce the topics it covers to students, researchers, and the general public. The video's transcript is also provided in full, with a portion provided below for preview:

"Since 1991, the international Banff Classification has been revisited every 2 years to integrate advances in clinical research into best-treatment practices for organ transplantation. At the 2017 Banff conference, 479 delegates from 23 countries reviewed two seminal concerns in the kidney-transplant field: how T cell-mediated rejection is related to inflammation in areas of interstitial fibrosis and tubular atrophy, and the evolution of molecular diagnostics, particularly for identifying antibody-mediated rejection. These discussions prompted significant updates to the Banff scheme. The relationship between i-IFTA severity and graft survival has been well established. Despite this, i-IFTA has previously been excluded as a diagnostic criterion of TCMR. Recent findings, however, suggest that inflammation in IFTA can be a manifestation of chronic active TCMR, particularly when other features of T cell-mediated alloimmunity, such as tubulitis, are present..."

The rest of the transcript, along with a link to the research itself, is available on the resource itself.

This patient education program explains clinical trials and answers some frequently asked questions. This is a MedlinePlus Interactive Health Tutorial from the National Library of Medicine, designed and developed by the Patient Education Institute.

This design course targets the solution of clinical problems by use of implants and other medical devices. Topics include the systematic use of cell-matrix control volumes; the role of stress analysis in the design process; anatomic fit, shape and size of implants; selection of biomaterials; instrumentation for surgical implantation procedures; preclinical testing for safety and efficacy, including risk/benefit ratio assessment evaluation of clinical performance and design of clinical trials. Student project materials are drawn from orthopedic devices, soft tissue implants, artificial organs, and dental implants.

This course is an introduction to the cross-cultural study of biomedical ethics, examining moral foundations of the science and practice of Western biomedicine through case studies of abortion, contraception, cloning, organ transplantation and other issues. It evaluates challenges that new medical technologies pose to the practice and availability of medical services around the globe, and to cross-cultural ideas of kinship and personhood. Also discussed are critiques of the biomedical tradition from anthropological, feminist, legal, religious, and cross-cultural theorists.

This resource is a video abstract of a research paper created by Research Square on behalf of its authors. It provides a synopsis that's easy to understand, and can be used to introduce the topics it covers to students, researchers, and the general public. The video's transcript is also provided in full, with a portion provided below for preview:

"A new study re-examining the validity of a major drug trial might have doctors rethinking how to treat heart attack survivors. Bolstered by the findings of a landmark clinical trial reported in 2015, the blood thinner ticagrelor has been increasingly prescribed by doctors to reduce the risk of heart attack in people with a history of heart problems. Now, researchers from France say those findings don’t apply to all patients who meet the original study’s criteria. That bias could prove critical for prescribers, who may witness more cases of serious bleeding and death among their patients than previously reported. The 2015 drug study, known as the PEGASUS trial, screened heart attack survivors from around the globe. Those selected for the trial had to be at least 65 years old, or at least 50 with diabetes. Results showed that, when combined with aspirin, ticagrelor significantly decreased the risk of stroke or a second heart attack. It did, however, increase the risk of major bleeding..."

The rest of the transcript, along with a link to the research itself, is available on the resource itself.

Background Many journals now require authors share their data with other investigators, either by depositing the data in a public repository or making it freely available upon request. These policies are explicit, but remain largely untested. We sought to determine how well authors comply with such policies by requesting data from authors who had published in one of two journals with clear data sharing policies. Methods and Findings We requested data from ten investigators who had published in either PLoS Medicine or PLoS Clinical Trials. All responses were carefully documented. In the event that we were refused data, we reminded authors of the journal's data sharing guidelines. If we did not receive a response to our initial request, a second request was made. Following the ten requests for raw data, three investigators did not respond, four authors responded and refused to share their data, two email addresses were no longer valid, and one author requested further details. A reminder of PLoS's explicit requirement that authors share data did not change the reply from the four authors who initially refused. Only one author sent an original data set. Conclusions We received only one of ten raw data sets requested. This suggests that journal policies requiring data sharing do not lead to authors making their data sets available to independent investigators.

This resource is a video abstract of a research paper created by Research Square on behalf of its authors. It provides a synopsis that's easy to understand, and can be used to introduce the topics it covers to students, researchers, and the general public. The video's transcript is also provided in full, with a portion provided below for preview:

"Statins are the first-line treatment for hypercholesterolemia in patients at high risk for cardiovascular mortality. But some patients require additional LDL cholesterol lowering to reach risk-stratified LDL-cholesterol levels or to further reduce cardiovascular risk. Clinical trials have demonstrated that the PCSK9 inhibitor evolocumab effectively lowers LDL cholesterol and is well tolerated. A new analysis of data from a subset of these trials extends these findings by evaluating LDL cholesterol lowering in patients receiving different evolocumab dosage regimens. Researchers performed a pooled analysis of data from four randomized 12-week phase 3 clinical trials comparing evolocumab to placebo or ezetimibe. Two subcutaneous evolocumab dosage regimens were examined: 140 mg every two weeks, and 420 mg monthly. Patients received evolocumab either as monotherapy or with background lipidlowering therapies, consisting of a statin alone or with ezetimibe..."

The rest of the transcript, along with a link to the research itself, is available on the resource itself.

This resource is a video abstract of a research paper created by Research Square on behalf of its authors. It provides a synopsis that's easy to understand, and can be used to introduce the topics it covers to students, researchers, and the general public. The video's transcript is also provided in full, with a portion provided below for preview:

"Exosomes are small membrane-bound vesicles that facilitate cell-to-cell communication by transporting biomolecules like proteins, RNA, and lipids. Due to their ubiquity and cargo-carrying abilities, exosomes have many potential uses in clinical medicine. First, they can be found in many biofluids like blood, urine, cerebrospinal fluid, saliva, and milk. This means they’re easy to collect and could be used in diagnostic testing as biomarkers. Beyond that, exosomes can be used to deliver cargo to key cells, either using naturally occurring exosomes or fashioning them into drug delivery vehicles. There are even promising results for exosome-based vaccines, not only for infectious diseases but anti-tumor vaccines as well. While the field has developed rapidly in recent decades, there is much more work to do. Specifically, researchers still need to elucidate the mechanisms of exosome transfer within the body..."

The rest of the transcript, along with a link to the research itself, is available on the resource itself.

This resource is a video abstract of a research paper created by Research Square on behalf of its authors. It provides a synopsis that's easy to understand, and can be used to introduce the topics it covers to students, researchers, and the general public. The video's transcript is also provided in full, with a portion provided below for preview:

"Stem cells are usually thought of as possible treatments for diseases like spinal cord injuries or type I diabetes, in which cells need to be replaced. But increasing evidence suggests they may be able to help with sepsis -- a life-threatening complication of infection. Sepsis is one of the most deadly and expensive syndromes, killing a quarter of a million people and incurring 20 billion dollars in hospital costs every year in the United States alone. Classically, sepsis has been thought of as a problem of an overactive immune system. As immune cells respond to infection, they unleash a torrent of inflammatory cytokines, or what’s called a cytokine storm, which can lead to organ failure. But recently, doctors have discovered that sepsis is more complicated, and if someone survives this early hyper-inflammatory stage, they are still at risk of succumbing later, when the syndrome switches over to being immune suppressive..."

The rest of the transcript, along with a link to the research itself, is available on the resource itself.

Healthcare Finance (15.482x) provides students with the background, resources, and framework to influence the healthcare industry. Topics include applying financial techniques such as portfolio theory, securitization, and option pricing to biomedical contexts to develop more efficient funding structures to reduce financial risks, lower the cost of capital, and bring more life-saving therapies to patients faster.
As part of the Open Learning Library, this course is free to use. You have the option to sign up and enroll if you want to track your progress, or you can view and use all the materials without enrolling.

Despite the potential benefits of sequential designs, studies evaluating treatments or experimental manipulations in preclinical experimental biomedicine almost exclusively use classical block designs. Our aim with this article is to bring the existing methodology of group sequential designs to the attention of researchers in the preclinical field and to clearly illustrate its potential utility. Group sequential designs can offer higher efficiency than traditional methods and are increasingly used in clinical trials. Using simulation of data, we demonstrate that group sequential designs have the potential to improve the efficiency of experimental studies, even when sample sizes are very small, as is currently prevalent in preclinical experimental biomedicine. When simulating data with a large effect size of d = 1 and a sample size of n = 18 per group, sequential frequentist analysis consumes in the long run only around 80% of the planned number of experimental units. In larger trials (n = 36 per group), additional stopping rules for futility lead to the saving of resources of up to 30% compared to block designs. We argue that these savings should be invested to increase sample sizes and hence power, since the currently underpowered experiments in preclinical biomedicine are a major threat to the value and predictiveness in this research domain.

This resource is a video abstract of a research paper created by Research Square on behalf of its authors. It provides a synopsis that's easy to understand, and can be used to introduce the topics it covers to students, researchers, and the general public. The video's transcript is also provided in full, with a portion provided below for preview:

"The ongoing Covid-19 pandemic has highlighted the importance of streamlining regulatory approval of medical products and technologies. Computational medicine, an emerging field integrating computational imaging and modelling, offers a pathway to refine, reduce, or replace otherwise costly and lengthy clinical trials – allowing them to be performed computationally, or in-silico. But reduced cost and time are only two benefits of in-silico trials. By performing trials on virtual populations, investigators can thoroughly explore extreme but plausible conditions that would not be feasible or ethical to consider in conventional clinical trials. They can also reduce the risk of human harm and the need for animal experiments. However, because in-silico trials are a new approach, the question of whether they can genuinely first replicate, and then expand upon, conventional trial results remains..."

The rest of the transcript, along with a link to the research itself, is available on the resource itself.

The Journal of Physiology and British Journal of Pharmacology jointly published an editorial series in 2011 to improve standards in statistical reporting and data analysis. It is not known whether reporting practices changed in response to the editorial advice. We conducted a cross-sectional analysis of reporting practices in a random sample of research papers published in these journals before (n = 202) and after (n = 199) publication of the editorial advice. Descriptive data are presented. There was no evidence that reporting practices improved following publication of the editorial advice. Overall, 76-84% of papers with written measures that summarized data variability used standard errors of the mean, and 90-96% of papers did not report exact p-values for primary analyses and post-hoc tests. 76-84% of papers that plotted measures to summarize data variability used standard errors of the mean, and only 2-4% of papers plotted raw data used to calculate variability. Of papers that reported p-values between 0.05 and 0.1, 56-63% interpreted these as trends or statistically significant. Implied or gross spin was noted incidentally in papers before (n = 10) and after (n = 9) the editorial advice was published. Overall, poor statistical reporting, inadequate data presentation and spin were present before and after the editorial advice was published. While the scientific community continues to implement strategies for improving reporting practices, our results indicate stronger incentives or enforcements are needed.

Background There is increasing interest to make primary data from published research publicly available. We aimed to assess the current status of making research data available in highly-cited journals across the scientific literature. Methods and Results We reviewed the first 10 original research papers of 2009 published in the 50 original research journals with the highest impact factor. For each journal we documented the policies related to public availability and sharing of data. Of the 50 journals, 44 (88%) had a statement in their instructions to authors related to public availability and sharing of data. However, there was wide variation in journal requirements, ranging from requiring the sharing of all primary data related to the research to just including a statement in the published manuscript that data can be available on request. Of the 500 assessed papers, 149 (30%) were not subject to any data availability policy. Of the remaining 351 papers that were covered by some data availability policy, 208 papers (59%) did not fully adhere to the data availability instructions of the journals they were published in, most commonly (73%) by not publicly depositing microarray data. The other 143 papers that adhered to the data availability instructions did so by publicly depositing only the specific data type as required, making a statement of willingness to share, or actually sharing all the primary data. Overall, only 47 papers (9%) deposited full primary raw data online. None of the 149 papers not subject to data availability policies made their full primary data publicly available. Conclusion A substantial proportion of original research papers published in high-impact journals are either not subject to any data availability policies, or do not adhere to the data availability instructions in their respective journals. This empiric evaluation highlights opportunities for improvement.

This course focuses on early-stage biotechnology companies with particular emphasis on understanding the underlying science, technology, and disease targets—together with the application of novel business structures and financing methods—to facilitate drug discovery, clinical development, and greater patient access to new therapies.   
The course was created for MITx as a collaboration between the Whitehead Institute and the Sloan School of Management and is now archived on the Open Learning Library (OLL), which is free to use. You have the option to sign up and enroll in each module if you want to track your progress, or you can view and use all the materials without enrolling.

Background The increased use of meta-analysis in systematic reviews of healthcare interventions has highlighted several types of bias that can arise during the completion of a randomised controlled trial. Study publication bias and outcome reporting bias have been recognised as a potential threat to the validity of meta-analysis and can make the readily available evidence unreliable for decision making. Methodology/Principal Findings In this update, we review and summarise the evidence from cohort studies that have assessed study publication bias or outcome reporting bias in randomised controlled trials. Twenty studies were eligible of which four were newly identified in this update. Only two followed the cohort all the way through from protocol approval to information regarding publication of outcomes. Fifteen of the studies investigated study publication bias and five investigated outcome reporting bias. Three studies have found that statistically significant outcomes had a higher odds of being fully reported compared to non-significant outcomes (range of odds ratios: 2.2 to 4.7). In comparing trial publications to protocols, we found that 40–62% of studies had at least one primary outcome that was changed, introduced, or omitted. We decided not to undertake meta-analysis due to the differences between studies. Conclusions This update does not change the conclusions of the review in which 16 studies were included. Direct empirical evidence for the existence of study publication bias and outcome reporting bias is shown. There is strong evidence of an association between significant results and publication; studies that report positive or significant results are more likely to be published and outcomes that are statistically significant have higher odds of being fully reported. Publications have been found to be inconsistent with their protocols. Researchers need to be aware of the problems of both types of bias and efforts should be concentrated on improving the reporting of trials.

Irreproducibility of preclinical biomedical research has gained recent attention. It is suggested that requiring authors to complete a checklist at the time of manuscript submission would improve the quality and transparency of scientific reporting, and ultimately enhance reproducibility. Whether a checklist enhances quality and transparency in reporting preclinical animal studies, however, has not been empirically studied. Here we searched two highly cited life science journals, one that requires a checklist at submission (Nature) and one that does not (Cell), to identify in vivo animal studies. After screening 943 articles, a total of 80 articles were identified in 2013 (pre-checklist) and 2015 (post-checklist), and included for the detailed evaluation of reporting methodological and analytical information. We compared the quality of reporting preclinical animal studies between the two journals, accounting for differences between journals and changes over time in reporting. We find that reporting of randomization, blinding, and sample-size estimation significantly improved when comparing Nature to Cell from 2013 to 2015, likely due to implementation of a checklist. Specifically, improvement in reporting of the three methodological information was at least three times greater when a mandatory checklist was implemented than when it was not. Reporting the sex of animals and the number of independent experiments performed also improved from 2013 to 2015, likely from factors not related to a checklist. Our study demonstrates that completing a checklist at manuscript submission is associated with improved reporting of key methodological information in preclinical animal studies.

This resource is a video abstract of a research paper created by Research Square on behalf of its authors. It provides a synopsis that's easy to understand, and can be used to introduce the topics it covers to students, researchers, and the general public. The video's transcript is also provided in full, with a portion provided below for preview:

"Levosimendan has been used in Europe for over 15 years in patients with acute heart failure, and when inotropic support is needed. The drug makes heart muscles more sensitive to calcium, allowing them to contract without the need for increased intracellular calcium and oxygen consumption, and also opens potassium channels inducing vasodilation. Because of these effects, levosimendan is considered helpful for patients undergoing cardiac surgery. Over 40 clinical trials have studied the drug in peri-operative settings and meta-analyses have suggested an overall beneficial outcome, particularly in patients with low ejection fraction. But recently, three large multi-center studies were neutral or inconclusive. To understand these conflicting results, a group of experts from eight European countries, including investigators from each of the three trials, met to discuss the discrepancies. The group reviewed each of the trials and searched for subgroup differences..."

The rest of the transcript, along with a link to the research itself, is available on the resource itself.