An example of medical device-based projection of clinical trial enrollment: Use of electrocardiographic data to identify candidates for a trial in acute coronary syndromes.

Background: To identify potential participants for clinical trials, electronic health records (EHRs) are searched at potential sites. As an alternative, we investigated using medical devices used for real-time diagnostic decisions for trial enrollment.

Methods: To project cohorts for a trial in acute coronary syndromes (ACS), we used electrocardiograph-based algorithms that identify ACS or ST elevation myocardial infarction (STEMI) that prompt clinicians to offer patients trial enrollment.

EFFICACY-TO-EFFECTIVENESS CLINICAL TRIALS.

Efficacy trials, which assess treatments in optimally selected patients under advantageous conditions for relatively short time periods, are necessary to gain regulatory approval for marketing. In contrast, effectiveness trials, which test treatments across a spectrum of patients in real-world conditions with follow-up periods that match typical treatment regimens, provide critical information on drug effects in those patients who may ultimately receive the treatment. We previously proposed a study design that integrates efficacy and effectiveness trials into a 2-component "efficacy-to-effectiveness (E2E) trial," in which if the initial efficacy trial component is positive, then the trial immediately and seamlessly transitions to the effectiveness trial component.

Clusterin and chemotherapy sensitivity under normoxic and graded hypoxic conditions in colorectal cancer.

Background And Aims: In vitro studies have shown that clusterin modulates treatment sensitivity in a number of human cancers; however, the interaction between clusterin expression and hypoxia in controlling treatment response in CRC has not previously been examined. The aim of this study was to assess the effect of clusterin overexpression in CRC cells on sensitivity to 5-fluorouracil (5-FU), oxaliplatin and FOLFOX treatment under normoxic and graded hypoxic conditions.

Methods: SW480 colon cancer cells were transfected with full length Clusterin cDNA to generate a clusterin overexpressing cell line.

Mitochondrial mutagenesis induced by tumor-specific radiation bystander effects.

The radiation bystander effect is a cellular process whereby cells not directly exposed to radiation display cellular alterations similar to directly irradiated cells. Cellular targets including mitochondria have been postulated to play a significant role in this process. In this study, we utilized the Random Mutation Capture assay to quantify the levels of random mutations and deletions in the mitochondrial genome of bystander cells.

Do radiation-induced bystander effects correlate to the intrinsic radiosensitivity of individuals and have clinical significance?

It is well known that patients can vary in their normal tissue response to radiotherapy, and this can be problematic. As a result, radiobiologists have been using in vitro models to assess variation in response and elucidate the genetic determinants of this variation. However, the clinical relevance of these models is currently unknown.

Radiation and chemotherapy bystander effects induce early genomic instability events: telomere shortening and bridge formation coupled with mitochondrial dysfunction.

The bridge breakage fusion cycle is a chromosomal instability mechanism responsible for genomic changes. Radiation bystander effects induce genomic instability; however, the mechanism driving this instability is unknown. We examined if radiation and chemotherapy bystander effects induce early genomic instability events such as telomere shortening and bridge formation using a human colon cancer explant model.

Increased topoisomerase IIalpha expression in colorectal cancer is associated with advanced disease and chemotherapeutic resistance via inhibition of apoptosis.

Topoisomerase IIalpha is a nuclear enzyme that regulates the tertiary structure of DNA. The influence of topoisomerase IIalpha gene (TOP2A) or protein alterations on disease progression and treatment response in colorectal cancer (CRC) is unknown. The study investigated the clinical relevance of topoisomerase IIalpha in CRC using in vivo and in vitro models.