Today, more than 75 percent of pharmaceutical drug trials in the United States are being conducted in the private sector. Once the sole province of academic researchers, these important studies are ...now being outsourced to non-academic physicians.
According to Jill A. Fisher, this major change in the way medical research is performed is the outcome of two problems in U.S. health care: decreasing revenue for physicians and decreasing access to treatment for patients. As physicians report diminishing income due to restrictive relationships with insurers, increasing malpractice insurance premiums, and inflated overhead costs to operate private practices, they are attracted to pharmaceutical contract research for its lucrative return. Clinical trials also provide limited medical access to individuals who have no or inadequate health insurance because they offer "free" doctors' visits, diagnostic tests, and medications to participants. Focusing on the professional roles of those involved, as well as key research practices, Fisher assesses the risks and advantages for physicians and patients alike when pharmaceutical drug studies are used as an alternative to standard medical care.
A volume in the Critical Issues in Health and Medicine series, edited by Rima D. Apple and Janet Golden
Randomised trials use the play of chance to assign participants to comparison groups. The unpredictability of the process, if not subverted, should prevent systematic differences between comparison ...groups (selection bias). Differences due to chance will still occur and these are minimised by randomising a sufficiently large number of people.
To assess the effects of randomisation and concealment of allocation on the results of healthcare studies.
We searched the Cochrane Methodology Register, MEDLINE, SciSearch and reference lists up to September 2009. In addition, we screened articles citing included studies (ISI Science Citation Index) and papers related to included studies (PubMed).
Eligible study designs were cohorts of studies, systematic reviews or meta-analyses of healthcare interventions that compared random allocation versus non-random allocation or adequate versus inadequate/unclear concealment of allocation in randomised trials. Outcomes of interest were the magnitude and direction of estimates of effect and imbalances in prognostic factors.
We retrieved and assessed studies that appeared to meet the inclusion criteria independently. At least two review authors independently appraised methodological quality and extracted information. We prepared tabular summaries of the results for each comparison and assessed the results across studies qualitatively to identify common trends or discrepancies.
A total of 18 studies (systematic reviews or meta-analyses) met our inclusion criteria. Ten compared random allocation versus non-random allocation and nine compared adequate versus inadequate or unclear concealment of allocation within controlled trials. All studies were at high risk of bias.For the comparison of randomised versus non-randomised studies, four comparisons yielded inconclusive results (differed between outcomes or different modes of analysis); three comparisons showed similar results for random and non-random allocation; two comparisons had larger estimates of effect in non-randomised studies than in randomised trials; and two comparisons had larger estimates of effect in randomised than in non-randomised studies.Five studies found larger estimates of effect in trials with inadequate concealment of allocation than in trials with adequate concealment. The four other studies did not find statistically significant differences.
The results of randomised and non-randomised studies sometimes differed. In some instances non-randomised studies yielded larger estimates of effect and in other instances randomised trials yielded larger estimates of effect. The results of controlled trials with adequate and inadequate/unclear concealment of allocation sometimes differed. When differences occurred, most often trials with inadequate or unclear allocation concealment yielded larger estimates of effects relative to controlled trials with adequate allocation concealment. However, it is not generally possible to predict the magnitude, or even the direction, of possible selection biases and consequent distortions of treatment effects from studies with non-random allocation or controlled trials with inadequate or unclear allocation concealment.
A majority of cancer diagnoses and deaths occur in patients age ≥ 65 years. With the aging of the US population, the number of older adults with cancer will grow. Although the coming wave of older ...patients with cancer was anticipated in the early 1980s, when the need for more research on the cancer-aging interface was recognized, many knowledge gaps remain when it comes to treating older and/or frailer patients with cancer. Relatively little is known about the best way to balance the risks and benefits of existing cancer therapies in older patients; however, these patients continue to be underrepresented in clinical trials. Furthermore, the available clinical trials often do not include end points pertinent to the older adult population, such as preservation of function, cognition, and independence. As part of its ongoing effort to advance research in the field of geriatric oncology, the Cancer and Aging Research Group held a conference in November 2012 in collaboration with the National Cancer Institute, the National Institute on Aging, and the Alliance for Clinical Trials in Oncology. The goal was to develop recommendations and establish research guidelines for the design and implementation of therapeutic clinical trials for older and/or frail adults. The conference sought to identify knowledge gaps in cancer clinical trials for older adults and propose clinical trial designs to fill these gaps. The ultimate goal of this conference series is to develop research that will lead to evidence-based care for older and/or frail adults with cancer.
There are many difficulties in undertaking independent clinical research without support from the pharmaceutical industry. In this retrospective observational study, some design characteristics, the ...clinical trial public register and the publication rate of noncommercial clinical trials were compared to those of commercial clinical trials. A total of 809 applications of drug‐evaluation clinical trials were submitted from May 2004 to May 2009 to the research ethics committee of a tertiary hospital, and 16.3% of trials were noncommercial. They were mainly phase IV, multicentre national, and unmasked controlled trials, compared to the commercial trials that were mainly phase II or III, multicentre international, and double‐blind masked trials. The commercial trials were registered and published more often than noncommercial trials. More funding for noncommercial research is still needed. The results of the research, commercial or noncommercial, should be disseminated in order not to compromise either its scientific or its social value.
Background
Participation of adolescents and young adults (AYAs) in oncology clinical trials is important to ensure adequate opportunities for AYA patients to contribute to, and benefit from, advances ...in cancer treatment.
Methods
Accrual data for National Cancer Institute (NCI) Cancer Therapy Evaluation Program (CTEP) cooperative group‐led treatment trials were examined to assess enrollment of newly diagnosed AYA patients (15–39 years) during the period 2004–2019, with particular interest in comparing enrollment before launch of the NCI National Clinical Trials Network (NCTN) to after. All phase 2, 2/3, and 3 trials activated during the period between January 1, 2004, and December 31, 2019, were identified (n = 1568) and reduced to a set of 304 that met predetermined criteria to focus on cooperative group‐led trials that involved therapy for newly diagnosed cancer and had age eligibility overlapping the AYA range. The proportion of AYA patients relative to total accrual, along with 95% bootstrapped CI was calculated for patients enrolled pre‐NCTN and post‐NCTN.
Results
AYA accrual comprised 9.5% (95% CI, 7.6–11.8) pre‐NCTN compared with 14.0% (95% CI, 9.9–18.3) post‐NCTN. The mean difference in proportions post‐NCTN compared with pre‐NCTN was 4.4% (0.7%–8.3%).
Conclusions
These results indicate an increase in AYA participation in trials conducted within the NCTN relative to the pre‐NCTN period. This suggests an awareness and utilization of NCTN trials for AYAs with cancer.
Lay summary
Five‐year relative survival for newly diagnosed adolescent and young adult (AYA) patients (15–39 years) with cancer is estimated at approximately 85% overall. However, outcomes tend to be worse for certain high‐risk AYA subsets, and AYAs remain challenged by multiple issues that could be addressed effectively through improved enrollment of AYAs onto clinical trials.
This study assessed participation of AYA patients newly diagnosed with cancer in National Cancer Institute (NCI) Cancer Therapy Evaluation Program‐sponsored clinical trials before and after launch of the NCI National Clinical Trials Network.
Trends in enrollment of adolescent and young adult (AYA) patients participating in National Cancer Institute (NCI) Cancer Therapy Evaluation Program (CTEP)‐sponsored cancer treatment trials during the period 2004–2019 are examined. Comparing enrollment prior to the launch of the NCI National Clinical Trials Network in 2014 to that after, a proportionate increase in enrollment of AYA patients is observed.
Introduction.
Cancer societies, research cooperatives, and countless publications have urged the development of clinical trials that facilitate the inclusion of older patients and those with ...comorbidities. We set out to determine the characteristics of currently recruiting clinical trials with hematological patients to assess their inclusion and exclusion of elderly patients.
Methods.
The NIH clinical trial registry was searched on July 1, 2013, for currently recruiting phase I, II or III clinical trials with hematological malignancies. Trial characteristics and study objectives were extracted from the registry website.
Results.
Although 5% of 1,207 included trials focused exclusively on elderly or unfit patients, 69% explicitly or implicitly excluded older patients. Exclusion based on age was seen in 27% of trials, exclusion based on performance status was seen in 16%, and exclusion based on stringent organ function restrictions was noted in 51%. One‐third of the studies that excluded older patients based on age allowed inclusion of younger patients with poor performance status; 8% did not place any restrictions on organ function. Over time, there was a shift from exclusion based on age (p value for trend <.001) toward exclusion based on organ function (p = .2). Industry‐sponsored studies were least likely to exclude older patients (p < .001).
Conclusion.
Notably, 27% of currently recruiting clinical trials for hematological malignancies use age‐based exclusion criteria. Although physiological reserves diminish with age, the heterogeneity of the elderly population does not legitimize exclusion based on chronological age alone. Investigators should critically review whether sufficient justification exists for every exclusion criterion before incorporating it in trial protocols.
The purpose of this study was to determine the characteristics of currently recruiting clinical trials with hematological patients to assess inclusion and exclusion of elderly patients. Notably, 27% of currently recruiting clinical trials for hematological malignancies use age‐based exclusion criteria. Investigators should critically review whether sufficient justification exists for every exclusion criterion before incorporating it in trial protocols.
High quality protocols facilitate proper conduct, reporting, and external review of clinical trials. However, the completeness of trial protocols is often inadequate. To help improve the content and ...quality of protocols, an international group of stakeholders developed the SPIRIT 2013 Statement (Standard Protocol Items: Recommendations for Interventional Trials). The SPIRIT Statement provides guidance in the form of a checklist of recommended items to include in a clinical trial protocol. This SPIRIT 2013 Explanation and Elaboration paper provides important information to promote full understanding of the checklist recommendations. For each checklist item, we provide a rationale and detailed description; a model example from an actual protocol; and relevant references supporting its importance. We strongly recommend that this explanatory paper be used in conjunction with the SPIRIT Statement. A website of resources is also available (www.spirit-statement.org). The SPIRIT 2013 Explanation and Elaboration paper, together with the Statement, should help with the drafting of trial protocols. Complete documentation of key trial elements can facilitate transparency and protocol review for the benefit of all stakeholders.
The critical need for pediatric research on drugs and biological products underscores the responsibility to ensure that children are enrolled in clinical research that is both scientifically ...necessary and ethically sound. In this chapter, we review key ethical considerations concerning the participation of children in clinical research. We propose a basic ethical framework to guide pediatric research, and suggest how this framework might be operationalized in linking science and ethics. Topics examined include: the status of children as a vulnerable population; the appropriate balance of risk and potential benefit in research; ethical considerations underlying study design, including clinical equipoise, placebo controls, and non-inferiority designs; the use of data monitoring committees; compensation; and parental permission and child assent to participate in research. We incorporate selected national (USA) and international guidelines, as well as regulatory approaches to pediatric studies that have been adopted in the USA, Canada, and Europe.
Background: SURMOUNT-4 was a Phase 3 clinical trial evaluating the safety and efficacy of tirzepatide in adults living with obesity or overweight. The method of delivery for tirzepatide was via a ...weekly, single-use injection pen device. The aim of this qualitative interview study was to better understand the ease-of-use of the pen device used to administer the study medication. Methods: Exit interviews were conducted with a random sample of US-based participants who had completed their Week 88 primary endpoint and Week 92 safety follow-up visits in SURMOUNT-4. A semi-structured discussion guide was used to understand the participant experience of the study, including use of the single-use pen device. Participants also completed an Injection Device Experience Questionnaire (ID-EQ) during their interview. As of May 30, 2023, interviews are on-going; n = 79 have been completed. The intended total sample size is n = 90 interviews. Results: Most participants reported that the single-use pen device was easy to use, and this was reflected in their responses to the IDEQ item "Overall, the device is easy to use": 91% responded "Strongly Agree", and 9% responded "Agree." Participants commented that the device was convenient due to being pre-filled and packaged as an allin-one device, that administration was simple and required minimal steps to inject each dose, that using the device took very little time, and that the needle was small and caused little to no pain. The requirement for the drug (and therefore the device) to be kept refridgerated was the key limitation mentioned. Conclusions: Qualitative exit interview methodology was utilized to understand participants' overall experience during SURMOUNT-4. Participants in the SURMOUNT-4 clinical trial found the single-use injection pen device to be easy to use and convenient.
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