Pretrial Screening Research Articles

Disparate impact of risk assessment instruments: A systematic review.

One concern about the use of risk assessment instruments in legal decisions is the potential for disparate impact by race or ethnicity. This means that one racial or ethnic group will experience harsher legal outcomes than another because of higher or biased risk estimates. We conducted a systematic review of the literature to synthesize research examining the real-world impact of juvenile and adult risk instruments on racial/ethnic disparities in legal decision making. Given the nature of research synthesis, we did not test formal hypotheses. Our systematic literature search as of July 2023 identified 21 articles that investigated the disparate impact of 13 risk assessment instruments on various legal outcomes. Most of these instruments were actuarial pretrial screening instruments. Our narrative synthesis indicated that there is not strong evidence of risk instruments contributing to greater system disparity. Ten articles indicated that adopting risk instruments did not create (or exacerbate preexisting) disparities, and eight articles found that instrument use reduced disparities in legal decision making. Three articles reported evidence of disparate impact of risk instruments; only one of these studies received a strong study quality assessment score. We observed a scarcity of high-quality articles that employed what we deem to be the gold standard approach for examining the disparate impact of risk instruments (i.e., pretest-posttest design). The evidence signals that risk instruments can contribute to reductions in disparities across multiple stages of legal decision making. Yet study quality remains low, and most research has been conducted on decisions during the pretrial stage. More rigorous research on disparate impact across diverse legal decision points and approaches to risk assessment is needed. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

A phase II trial of induction systemic mFOLFIRINOX followed by hepatic arterial infusion of floxuridine and dexamethasone given concurrently with systemic mFOLFIRI as a first-line therapy in patients with unresectable liver-dominant intrahepatic cholangiocarcinoma (HELIX-1).

511 Background: Most patients with intrahepatic cholangiocarcinoma (ICC) have unresectable or multifocal liver-dominant disease. Survival after first-line systemic therapy remains poor, with median progression-free (mPFS) and overall survival of 7.2 and 12.8 months, respectively. Hepatic arterial infusion (HAI) therapy with floxuridine maximizes liver-specific treatment with minimal systemic toxicity and potentially offers improved disease control when combined with systemic therapy. Methods: HELIX-1 (NCT04251715) is an investigator-initiated, first-line, single-center, single-arm phase II clinical trial for patients with liver-dominant unresectable or multifocal ICC. The trial was designed with a patient safety run-in evaluating toxicity from the combined therapy. Pre-trial screening included laparoscopy, biopsies, and PET/CT. Eligible patients were treated with systemic mFOLFIRINOX for 4 cycles in order to select those likely to benefit from HAI. Patients with disease control on restaging proceeded to HAI pump placement and treatment with HAI floxuridine for 14 days followed by systemic mFOLFIRI on a 28-day cycle. The co-primary objectives were to assess safety of the combined therapeutic strategy and the disease control rate (DCR) at 6 months (RECIST v1.1) at end of trial (EOT). Results: A total of n=5 patients with liver-only ICC enrolled in the trial and completed the entire study protocol. The median age was 60 years (range 42-69) with a dominant lesion size of 9.8cm (range 8.4-14.5). All patients had both right and left hemiliver involvement with a median of 9 intrahepatic tumors (range 1-15). No patients experienced grade 3 or 4 adverse events, or hepatic dysfunction leading to cessation of HAI therapy. The DCR at 6 months was 100%, with a mPFS of 18.2 months. All five patients achieved partial radiographic response (PR) while receiving HAI therapy, and remain alive with liver-only disease at a median of 18.4 months (range 12.7-20) after study enrollment. After continuing treatment with HAI and systemic mFOLFIRI beyond the EOT, two patients transitioned to HAI treatment only and then to biochemical and radiographic surveillance without therapy after demonstrating PR and CA19-9 normalization. Conclusions: Integration of HAI floxuridine with mFOLFIRI following mFOLFIRINOX induction for patients with liver-only advanced ICC is well-tolerated and demonstrates longer DCR in comparison to historical controls. The combined regimen minimized systemic toxicity and allowed a large proportion of patients to transition to liver-only HAI treatment with maintained disease control. Future directions include combining HAI with new first-line systemic regimens for patients with advanced ICC. Clinical trial information: NCT04251715 .

Safety and Feasibility of a 16-Week Progressive Exercise Intervention in Treatment Naïve Chronic Lymphocytic Leukaemia

A growing body of evidence from preclinical and human epidemiology studies of multiple cancer types indicate that physical activity can delay or avert the outgrowth of cancer, in a mechanistic process that may involve exercise-induced alterations to anti-cancer immunity. Many Chronic Lymphocytic leukaemia (CLL) patients present with asymptomatic, early-stage disease that is monitored until disease progression. Thus, exercise may be an effective way to manage disease burden and delay progression in treatment naïve CLL. The primary objective of this pilot study was to investigate the safety and feasibility of an exercise programme in people with treatment naïve CLL, and preliminarily explore the effects of exercise training on CLL counts, body composition, cardiorespiratory fitness, and immune cell phenotypes including T-cells. We approached N = 100 treatment naïve CLL patients (Binet stage A and B) (Figure 1). Trial uptake was 40%, thus n = 40 participants with treatment naïve CLL were screened. After assessing suitability for exercise (e.g., resting electrocardiogram and other safety tests), n = 11 participants were excluded - the majority of these, n = 9, were due to the presence of cardiac abnormalities. Consequently, n = 28 participants were randomised into a 16-week, home-based, supervised, personalised, progressive exercise intervention ( n = 14: mean ± SD: age = 62 ± 12 years) or 16-weeks of usual care, control group ( n = 14: mean ± SD: age = 61 ± 10 years). The overall retention rate was 86%, with 79% of the exercise group and 93% of the control group completing the trial. Adherence to the exercise intervention was 92 ± 8%. One serious adverse event was reported (hospitalisation for pneumonia) that was unrelated to the trial and one adverse event was reported (syncope following exercise) that was related to the trial. Together, this evidence indicates that exercise training is both safe and feasible in people with treatment naïve CLL who passed pre-trial screening. The exercise intervention elicited a 2% increase in DEXA-derived lean mass in the exercise group compared to a 0.4% decrease in the control group ( p = .01) (Table 1). DEXA-derived total body fat percentage decreased by 4% and 1% and fat mass decreased by 3% and 2% ( p < .05) respectively in the exercise and control groups but there was no significant difference between the groups ( p > 0.05). Resting systolic and diastolic blood pressure was lower at post-intervention in both groups ( p < .05); the exercise group reduced systolic and diastolic blood pressure by 5% and 2% respectively and the control group reduced by 6% and 7% respectively, but there was no significant difference between groups ( p>0.05) suggesting the observed changes could be the result of “white coat hypertension” pre-intervention. Additionally, no changes were observed for whole-body mass, BMI, bone mineral density, resting heart rate, or measures of cardiorespiratory fitness (all p>0.05). This trial provided a unique opportunity to investigate the effects of regular exercise on neoplastic activity in humans (i.e., CLL counts) without the confounding presence of anti-cancer therapy. Resting blood samples collected pre- and post-intervention were analysed by flow cytometry to enumerate CD5 +CD19 + CLL cells clonally restricted to kappa or lambda. No differences were observed for clonal CLL cells over time or between conditions ( p>0.05) (Table 1). We also analysed resting blood samples collected pre- and post-intervention by flow cytometry to enumerate T cell subsets. No statistically significant changes were observed between conditions pre-intervention to post-intervention for CD4 + or CD8 + T-cell subsets including, naïve (CD27 +CD45RA +), stem cell-like memory (CD27 +CD45RA +CD127 +CD95 +), central memory (CD27 +CD45RA -), effector memory (CD27 -CD45RA -), EMRAs (CD27 -CD45RA +) or exhausted T-cells (PD1 +, Tim3 +) or FoxP3 T-regulatory cells (CD4 +CD127 lowCD25 +FoxP3 +) (all p>0.05). Our results show that exercise is safe and feasible in people with treatment naïve CLL who passed pre-trial screening. In addition, exercise training increased lean mass. No changes were observed to CLL cells. The latter finding is unsurprising given the poorly immunogenic profile of CLL.

Error Aversions and Due Process

William Blackstone famously expressed the view that convicting the innocent constitutes a much more serious error than acquitting the guilty. This view is the cornerstone of due process protections for those accused of crimes, giving rise to the presumption of innocence and the high burden of proof required for criminal convictions. While most legal elites share Blackstone’s view, the citizen jurors tasked with making due process protections a reality do not share the law’s preference for false acquittals over false convictions. Across multiple national surveys sampling more than 12,000 people, we find that a majority of Americans consider false acquittals and false convictions to be errors of equal magnitude. Contrary to Blackstone, most people are unwilling to err on the side of letting the guilty go free to avoid convicting the innocent. Indeed, a sizeable minority view false acquittals as worse than false convictions; this group is willing to convict multiple innocent persons to avoid letting one guilty person go free. These value differences translate into behavioral differences: we show in multiple studies that jury-eligible adults who reject Blackstone’s view are more accepting of prosecution evidence and are more conviction-prone than the minority of potential jurors who agree with Blackstone. These findings have important implications for our understanding of due process and criminal justice policy. Due process currently depends on jurors faithfully following instructions on the burden of proof, but many jurors are not inclined to hold the state to its high burden. Courts should do away with the fiction that the reasonable doubt standard guarantees due process and consider protections that do not depend on jurors honoring the law’s preference for false acquittals, such as more stringent pretrial screening of criminal cases and stricter limits on prosecution evidence. Further, the fact that many people place crime control on par with, or above, the need to avoid wrongful convictions helps explain divisions in public opinion on important policy questions like bail and sentencing reform. Criminal justice proposals that emphasize deontic concerns without addressing consequentialist concerns are unlikely to garner widespread support.

Abstract 1588: Discordance of HER2 expression and/or amplification on repeat testing

Abstract Purpose: Evaluation of human epidermal growth factor receptor 2 (HER2) expression/amplification status is critical when considering HER2-targeted therapies. We sought to assess discordance of HER2 status in patients with HER2-amplified/expressing solid tumors who underwent a repeat biopsy for pre-trial screening. Methods: Consenting patients with solid tumors and documented HER2 expression by immunohistochemistry (IHC) or amplification by fluorescent in situ hybridization/next generation sequencing (FISH/NGS) on historical local testing underwent a new biopsy for central reevaluation of HER2 status. Samples were assessed for HER2 expression by IHC and ERBB2 amplification by FISH. Specimens were reviewed by a central laboratory. Patients with HER2 overexpression by IHC (3+) or ERBB2 amplification by FISH/NGS on local testing were assessed for HER2 discordance on central testing (not amplified by FISH and/or not 3+ by IHC on central reevaluation). Results: 56 patients with HER2 expression/amplification on local testing with a median age of 59.5 years and 30 (53.6%) females underwent biopsy and repeat HER2 testing. Median time between consent and treatment for those enrolled was 26 days (range 8-83 days). Twelve cancers were represented, including 12 breast (21.4%), 6 gastroesophageal (10.7%), and 6 biliary tract (10.7%). 31 patients (55.4%) received HER2-targeted therapies between local and central testing. Local assessment of HER2 status on archival tissue was performed in 36 (64.3%) patients by IHC, 27 (48.2%) by FISH, and 18 (32.1%) by NGS. There were 23 patients who were IHC 3+ on local testing and of these, 15 (65.2%) were 3+, 4 (17.4%) were 2+ (3 FISH +), 2 (8.7%) were 1+ (FISH-), and 2 (8.7%) had 0 HER2 expression on central IHC. Of 4 patients that were 2+ without amplification on local testing, 3 were 2+ and 1 was 1+ on central IHC. In 18 patients with ERBB2 amplification on local NGS, 14 (77.8%) were 3+ on central IHC and 17 (94.4%) were ERBB2 amplified by FISH. Of the 51 patients who were 3+ by IHC or amplified by FISH/NGS on local testing, 14 (27.5%) were discordant on central reevaluation. Discordance in HER2 status was found in 5/12 (41.7%) gastroesophageal, 2/9 (22.2%) breast, and 1/7 (14.3%) colorectal tumors. Discordant HER2 status was observed in 9 (30.0%) of 30 cases who received intervening HER2-targeted therapy and in 5 (23.8%) of 21 patients who did not. Of 14 patients with HER2 discordance, 7 were potentially eligible for trial enrollment based on local testing but ineligible based on central HER2 testing. Conclusions: Discordance in HER2 status on repeat biopsy is not infrequent in patients with tumors previously identified as HER2-positive/expressing. Discordance is not limited to patients with prior HER2-targeted therapy and could have therapeutic implications. Biomarker reevaluation may be warranted when considering HER2-targeted therapies but needs to be balanced with a slight delay in treatment initiation. Citation Format: Timothy D. DiPeri, Kathleen Kong, Daniel D. Karp, Jaffer A. Ajani, Shubham Pant, Sarina A. Piha-Payl, Ecaterina E. Dumbrava, Funda Meric-Bernstam. Discordance of HER2 expression and/or amplification on repeat testing [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1588.

Medical Malpractice System in the United States of America: Lesson to Learn for Indonesia

A system that serves the liability and settlement of medical malpractice disputes or commonly referred to as medical malpractice system has been established in many countries to respond the rise of medical malpractice claims against doctors. Medical malpractice system in the United States of America (the USA) has been relatively well developed as compared to other countries. Beside adopting pretrial screening process in medical malpractice litigation, various methods of alternative to litigation have been developed in the USA. This paper aims to explore the development of the medical malpractice system in the USA and to see the possibility for Indonesia to learn. This normative legal research relies on the secondary data especially which were collected from online sources. It is found that there are some initiatives in the USA that can be adopted by Indonesia for improving its medical malpractice system, especially the establishment of pretrial screening panel. It is expected that pretrial screening process can eliminate meritless claims which later may reduce unnecessary legal actions against doctors.

Intranasal oxytocin as a treatment for chronic pelvic pain: A randomized controlled feasibility study.

To investigate the effect of intranasal oxytocin on chronic pelvic pain in a randomized, double-blind, within-subject crossover trial. Aims included: (1) determine intranasal oxytocin's effect on pain intensity and pain interference relative to placebo; (2) assess feasibility and acceptability. Women with chronic pelvic pain were recruited from chronic pain and gynecology clinics between September 2017 and December 2018. Pain was recorded at pre-trial screening, and while administering intranasal oxytocin and placebo. Pain and pain-related interference were measured using the Brief Pain Inventory - Short Form. Feasibility and acceptability were measured using validated measures and interviews. Twenty-one women were randomized with sufficient data available from 12 to permit analyses. Relative to placebo, a 2-week course of oxytocin administration resulted in improvement in pain severity with no effect on pain-related interference. This effect was driven by four women who demonstrated a minimal clinically significant improvement in pain following intranasal oxytocin (no women met this threshold for placebo). Adherence to dosing was excellent and occurrence of adverse effects did not differ between oxytocin and placebo. Intranasal oxytocin may represent an adjuvant analgesic that could result in a minimal clinically significant improvement in pain among one in three women with chronic pelvic pain. Registration: ClinicalTrials.gov (Registration# NCT02888574).

Analysis of Heterozygous PRKN Variants and Copy-Number Variations in Parkinson's Disease.

Biallelic PRKN mutation carriers with Parkinson's disease (PD) typically have an earlier disease onset, slow disease progression, and, often, different neuropathology compared to sporadic PD patients. However, the role of heterozygous PRKN variants in the risk of PD is controversial. Our aim was to examine the association between heterozygous PRKN variants, including single-nucleotide variants and copy-number variations (CNVs), and PD. We fully sequenced PRKN in 2809 PD patients and 3629 healthy controls, including 1965 late-onset (63.97 ± 7.79 years, 63% men) and 553 early-onset PD patients (43.33 ± 6.59 years, 68% men). PRKN was sequenced using targeted next-generation sequencing with molecular inversion probes. CNVs were identified using a combination of multiplex ligation-dependent probe amplification and ExomeDepth. To examine whether rare heterozygous single-nucleotide variants and CNVs in PRKN are associated with PD risk and onset, we used optimized sequence kernel association tests and regression models. We did not find any associations between all types of PRKN variants and risk of PD. Pathogenic and likely-pathogenic heterozygous single-nucleotide variants and CNVs were less common among PD patients (1.52%) than among controls (1.8%, false discovery rate-corrected P = 0.55). No associations with age at onset and in stratified analyses were found. Heterozygous single-nucleotide variants and CNVs in PRKN are not associated with PD. Molecular inversion probes allow for rapid and cost-effective detection of all types of PRKN variants, which may be useful for pretrial screening and for clinical and basic science studies targeting specifically PRKN patients. © 2020 International Parkinson and Movement Disorder Society.

The Medical Review Panel in Louisiana Neurosurgery and Beyond.

For the past several decades, medical malpractice claims in the state of Louisiana have been screened by a pretrial medical review panel (MRP). Composed of 3 physicians and 1 attorney, these panels are a method of filtering nonmeritorious lawsuits while expediting creditable claims. Currently, 14 jurisdictions in the United States require medical liability/malpractice cases be heard by an MRP or screening panel prior to trial. In this article, we review the MRP process in Louisiana and compare it to those in other states. Data are presented for the past 10 yr of malpractice claims in Louisiana with an emphasis on the neurosurgery specialty. Finally, the benefits and challenges of pretrial screening panels are discussed.

Patterns of participation over four rounds of annual fecal immunochemical test-based screening for colorectal cancer: what predicts rescreening?

BackgroundParticipation at the recommended intervals is critical for screening to be effective in reducing colorectal cancer (CRC) incidence. This study describes patterns of screening participation over four rounds of fecal immunochemical testing (FIT) to identify whether demographic variables and prior screening satisfaction are significantly associated with patterns of re-participation.MethodsBaseline surveys were mailed to 4000 South Australians randomly selected from the electoral-roll. Respondents (n = 1928/48.2%) were offered four annual FIT rounds. Screening participation and satisfaction at each round were recorded.ResultsStudy participation was 58.5, 66.9, 73.1 and 71.4% respectively over four rounds. Three participation patterns were described: consistent participation (43.1%), consistent non-participation (26.4%) and inconsistent participation (changeable; 30.5%), including intermittent and sustained change patterns. Sustained change described those who changed participatory behavior and then maintained for at least two rounds (n = 375/19.5%). Older people, and those not working were most likely to sustain participation. Younger invitees, especially men, were more likely to change participatory behavior and sustain the change. People with higher disadvantage, less education, not working and with no prior (pre-trial) screening experience were more likely to start participating and drop out. People dissatisfied with a prior screening test, including finding aspects embarrassing or unpleasant, were also more likely not to participate in annual screening or to drop out.ConclusionsThe findings identify those at risk of non- or inconsistent participation in rescreening. They should aid targeting of interventions for demographic groups at risk and ensuring screening experiences are not perceived as unpleasant or difficult.

KKN Management Center and Region Development Research Institutions and Community Devotion State University of Yogyakarta

(KKN) is held in Kradenan Hamlet, Srimulyo Village, Piyungan Sub-district, Bantul District, Special Province of Yogyakarta, Real Working Lecture (KKN), Kradenan Hamlet consists of 4 RT. The population of approximately 173 families. The inhabitants of Kradenan are all Muslims, and the majority live as factory workers. The purpose of KKN is in Kradenan Hamlet, to explore, to develop the potential of the Kradenan Hamlet community, and to advance the thinking of the people of Kradenan Hamlet. The Real Work Lecture Program has been implemented in the Kradenan Hamlet pre-trial training and screening of Java-uploaded films. The purpose of the pre-trial training is to explore and develop the potential of Kradenan Hamlet people, and the purpose of holding Javanese uploading films is to give awareness since the early importance of paying attention and doing the uploads to anyone and anywhere. Children are able to understand the pranatacara technique properly and correctly. Children have also started to get used to being in line with the uploads to anyone and wherever they are. Programs held in the right sense are held in Kradenan Hamlet. One of the programs that are in line with the Hamur Hamada people's desires are pre-training training and targeted to adolescents, young people who aim to have the next generation and can open the insight to the community in seeking additional side work.
 
 Keywords: KKN, Bantul Regency, Kradenan Village, Srimulyo Village, Piyungan Sub-district, Pranatanacara Training.

Abstract A11: NGS-based tumor genomic profiling to identify ovarian cancer patients who benefit from the PARP inhibitor rucaparib.

Abstract Background: PARP inhibitors (PARPi) are synthetically lethal to tumor cells with homologous recombination deficiency (HRD). HRD can result from deleterious BRCA1/2 mutations (BRCAmut) or other mechanisms that have not been fully elucidated. Regardless of mechanism, HRD leads to a common phenotype of genome-wide loss of heterozygosity (LOH). It has been hypothesized that this genomic phenotype can be used to identify BRCA wild-type (BRCAwt) HRD tumors likely sensitive to PARPi. Using comprehensive next generation sequencing (NGS)-based tumor genomic profiling, we developed an HRD assay for potential use as a companion diagnostic for rucaparib in high-grade ovarian cancer (HGOC) by combining tumor BRCA1/2 status and quantification of genomic LOH. Methods: In the phase 2 study ARIEL2 Part 1 (NCT01891344), pre-treatment screening biopsies and archival formalin-fixed paraffin embedded tumor specimens were profiled using Foundation Medicine's NGS-based HRD assay, which detects all classes of genomic alterations, including base substitutions, insertions/deletions, and homozygous deletions in BRCA1/2. Genomic LOH was assessed by sequencing >3,500 evenly-distributed single nucleotide polymorphisms across the genome and quantifying the extent of genomic LOH. A pre-specified genomic LOH cutoff was determined using publicly available SNP array data of ovarian tumors to predict platinum sensitivity as a surrogate marker for PARPi sensitivity. Response was assessed by RECIST v1.1 and GCIG CA-125 response criteria. Results: As of July 1 2015, 195 archival tumor and 152 screening biopsy samples (142 matched pairs) from 206 HGOC patients enrolled (204 patients treated) in ARIEL2 Part 1 were successfully profiled using the NGS-based HRD assay. Some screening biopsies were not suitable for successful NGS-based HRD assessment primarily because of insufficient tumor nuclei or inadequate tumor volume. Most matched pairs of archival and pre-trial screening samples exhibited similar genomic LOH profiles (r=0.86); however, 14% of screening samples had higher genomic LOH compared with archival samples collected more than one year earlier. All BRCA1/2 germline and somatic mutated tumors had high genomic LOH in the screening samples. Receiver operating characteristic analysis of genomic LOH showed utility in identifying RECIST/CA-125 responders to rucaparib (AUC=0.72, p<1e-4), with slightly better predictive utility using screening samples compared to archival samples (AUC=0.72 vs 0.69). Using the pre-specified genomic LOH cutoff, high genomic LOH tumors were detected in 54% of evaluable BRCAwt patients; significantly different overall response rates were found in patients with high vs low genomic LOH tumors (48% vs 26%; chi-square p=0.0074). Conclusions: We developed an NGS-based HRD assay that assesses tumor BRCA1/2 and genomic LOH to prospectively identify HGOC patients who may benefit from rucaparib treatment. The optimized NGS-based HRD assay will be prospectively tested in the ongoing portion of the phase 2 study (ARIEL2 Part 2, NCT01891344) and a phase 3 maintenance study (ARIEL3, NCT01968213) that will investigate rucaparib in HGOC. Citation Format: Iain A. McNeish, Kevin K. Lin, James X. Sun, Sandra Goble, Amit Oza, Robert L. Coleman, Clare L. Scott, Gottfried Konecny, Anna V. Tinker, David M. O'Malley, Rebecca Kristeleit, Ling Ma, James D. Brenton, Katherine Bell-McGuinn, Ana Oaknin, Alexandra Leary, Elaina Mann, Heidi Giordano, Roman Yelensky, Mitch Raponi, Elizabeth Swisher. NGS-based tumor genomic profiling to identify ovarian cancer patients who benefit from the PARP inhibitor rucaparib. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: Exploiting Vulnerabilities; Oct 17-20, 2015; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(2 Suppl):Abstract nr A11.

Understanding Russia’s Low Rate of Acquittal: Pretrial Screening and the Problem of Accusatorial Bias

The Soviet Union and post-Soviet Russia alike have had extremely low rates of acquittal in criminal cases, which conventional wisdom associates with an accusatorial bias. But other countries like Canada, Germany, The Netherlands, and France also have low rates of acquittal without the perception of bias. This article argues that the key difference lies in the presence or absence of pretrial screening—through the withdrawal of charges, diversion, and/or dispositions imposed by prosecutors. After a brief history of the low acquittal rate in Russia, the article documents the use of prosecutorial discretion to screen cases before trial in those four Western countries, especially through the exercise by prosecutors of quasi-judicial functions. The article goes on to demonstrate the absence of significant pretrial filtering of cases in Russia and to explore the implications for understanding the rate of acquittal.

The impact of PLCO control arm contamination on perceived PSA screening efficacy

To quantify the extent to which a clinically significant prostate cancer mortality reduction due to screening could have been masked by control arm screening (contamination) in the Prostate, Lung, Colorectal, and Ovarian (PLCO) trial. We used three independently developed models of prostate cancer natural history to conduct a virtual PLCO trial. Simulated participants underwent pre-trial screening based on population patterns. The intervention arm followed observed compliance during the trial then resumed population screening. A contaminated control arm followed observed contamination during the trial then resumed population screening, while an uncontaminated control arm discontinued screening upon entry. We assumed a clinically significant screening benefit, applied population treatments and survival patterns, and calculated mortality rate ratios relative to the contaminated and uncontaminated control arms. The virtual trial reproduced observed incidence, including stage and grade distributions, and control arm mortality after 10years of complete follow-up. Under the assumed screening benefit, the three models found that contamination increased the mortality rate ratio from 0.68-0.77 to 0.86-0.91, increased the chance of excess mortality in the intervention arm from 0-4% to 15-28%, and decreased the power of the trial to detect a mortality difference from 40-70% to 9-25%. Our computer simulation models indicate that contamination substantially limited the ability of the PLCO to identify a clinically significant screening benefit. While the trial shows annual screening does not reduce mortality relative to population screening, contamination prevents concluding whether screening reduces mortality relative to no screening.

Centrale coördinatie van een multicenterstudie als alternatief voor betaling per patiënt

Objective: Multicenter clinical trials can be organized in different ways. Multiple centers participated in the HEALTH trial (Hip Fracture Evaluation with ALternatives of Total Hip Arthroplasty versus Hemi- Arthroplasty). For the Dutch sites most study tasks are managed by a central trial coordinator, whereas Canadian and US sites use local study coordinators. The aim of this study was to analyze how these strategies affected trial performance.Design: Prospective observational study.Method: Data related to ethics approval, trial startup time, inclusion rate and percentage of completed follow-ups were collected for each hospital and compared. Data from pre-trial screening were compared with actual inclusion rates.Results: The median start-up time of the trial after obtaining ethics approval was shorter in the Netherlands than in Canada and the US (4.6 versus 11.6 weeks).The inclusion rate was similar in both groups (0.62 versus 0.64/month). The median percentage of enrolled patients in the Netherlands was 27.3% versus 17.0% in Canada/US. The actual inclusion rates were lower than expected from pre-trial screening. The percentage of effectuated follow-up visits was > 90% in both groups.Conclusion: In this study, central trial coordination contributed to faster trial start-up and higher inclusion rates, but had no effect on the effectuated followup visits. Central coordination is therefore a suitable alternative for appointing these tasks to local research assistants and per patient payment. Central coordination enables non-academic hospitals to participate in clinical trials. Limiting conditions for central coordination are budget availability, a manageable number of patients, and a manageable distance between participating sites.

Central coordination as an alternative for local coordination in a multicenter randomized controlled trial: the FAITH trial experience

BackgroundSurgeons in the Netherlands, Canada and the US participate in the FAITH trial (Fixation using Alternative Implants for the Treatment of Hip fractures). Dutch sites are managed and visited by a financed central trial coordinator, whereas most Canadian and US sites have local study coordinators and receive per patient payment. This study was aimed to assess how these different trial management strategies affected trial performance.MethodsDetails related to obtaining ethics approval, time to trial start-up, inclusion, and percentage completed follow-ups were collected for each trial site and compared. Pre-trial screening data were compared with actual inclusion rates.ResultsMedian trial start-up ranged from 41 days (P25-P75 10-139) in the Netherlands to 232 days (P25-P75 98-423) in Canada (p = 0.027). The inclusion rate was highest in the Netherlands; median 1.03 patients (P25-P75 0.43-2.21) per site per month, representing 34.4% of the total eligible population. It was lowest in Canada; 0.14 inclusions (P25-P75 0.00-0.28), representing 3.9% of eligible patients (p < 0.001). The percentage completed follow-ups was 83% for Canadian and Dutch sites and 70% for US sites (p = 0.217).ConclusionsIn this trial, a central financed trial coordinator to manage all trial related tasks in participating sites resulted in better trial progression and a similar follow-up. It is therefore a suitable alternative for appointing these tasks to local research assistants. The central coordinator approach can enable smaller regional hospitals to participate in multicenter randomized controlled trials. Circumstances such as available budget, sample size, and geographical area should however be taken into account when choosing a management strategy.Trial RegistrationClinicalTrials.gov: NCT00761813

Assessing contamination and compliance in the prostate component of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial

Recently, the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial published 7-year complete prostate cancer mortality results, which showed no benefit of screening with prostate specific antigen (PSA) and digital rectal examination (DRE). An issue of concern was the substantial level of 'contamination', or use of PSA and DRE in control arm men. To provide a detailed description of contamination in PLCO. Surveys inquiring about the most recent PSA and DRE use were given to a sample of control arm men throughout the screening phase of PLCO (years 0-5). A probability model was utilized to translate survey results into actual frequency counts of tests. To assess the impact of contamination, Surveillance, Epidemiology, and End (SEER) incidence rates from the pre-screening era (1985-1987) as well as contemporaneous rates, were applied to PLCO person-years of observation. Results Of 38,350 control arm men, 2427 were surveyed. Pre-trial screening and college education were statistically significantly associated with increased contamination rates. The estimated mean number of screening PSAs (DREs) in the control arm was 2.7 (1.1); this compares to 5.0 (3.5) in the screened arm. 1984 and 2538 prostate cancers were observed in the control and screened arms, respectively, during the screening phase. In the absence of screening, 960 and 949 would have been expected; with contemporaneous incidence rates, 1630 and 1611 were expected. Due to the limitations of the surveys, in terms of both reach and scope, the exact level of PSA and DRE use in control arm men cannot be known. Use of prostate screening by control arm men was substantial, but also substantially less than in screened arm men. Detailed quantitative analyses of screening use across arms are critical for understanding current and future findings from the prostate component of PLCO.

Demonstrations Sub for Medical Liability Reform

Demonstrations Sub for Medical Liability Reform

Defensive Medicine and Tort Reform: A Wide View

Defensive Medicine and Tort Reform: A Wide View

Methodologies for evaluating HIV prevention intervention (populations and epidemiologic settings)

There have been over 30 HIV-prevention trials of which only four reported evidence of efficacy. The reasons for these negative findings may be due to ineffective interventions, but in part reflect the inappropriate selection of study populations and epidemiologic settings. Three trials showed that male circumcision reduces HIV acquisition in men by 50-60%. In contrast, seven out of eight trials of bacterial and viral sexually transmitted infection (STI) control, and multiple microbicide trials show no efficacy for HIV prevention. Several microbicide trials found vaginal irritation and microulceration, which may increase HIV risk. Three vaccine trials failed to show efficacy and one trial suggested increased HIV risk in a subgroup of uncircumcised men. The failure of most prevention trials reflects inadequate pretrial screening of potentially efficacious interventions, insufficient information on background HIV incidence, selection of high-risk populations with poor compliance and lack of generalizability, and treatment interruption during pregnancy all of which compromise power.