Background
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.
Objectives
To assess the effects of randomisation and concealment of allocation on the results of healthcare studies.
Search methods
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).
Selection criteria
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.
Data collection and analysis
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.
Main results
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.
Authors' conclusions
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.
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.
The phenomenal growth of global pharmaceutical sales and the quest for innovation are driving an unprecedented search for human test subjects, particularly in middle- and low-income countries. Our ...hope for medical progress increasingly depends on the willingness of the world's poor to participate in clinical drug trials. While these experiments often provide those in need with vital and previously unattainable medical resources, the outsourcing and offshoring of trials also create new problems. In this groundbreaking book, anthropologist Adriana Petryna takes us deep into the clinical trials industry as it brings together players separated by vast economic and cultural differences. Moving between corporate and scientific offices in the United States and research and public health sites in Poland and Brazil,When Experiments Traveldocuments the complex ways that commercial medical science, with all its benefits and risks, is being integrated into local health systems and emerging drug markets.
Providing a unique perspective on globalized clinical trials,When Experiments Travelraises central questions: Are such trials exploitative or are they social goods? How are experiments controlled and how is drug safety ensured? And do these experiments help or harm public health in the countries where they are conducted? Empirically rich and theoretically innovative, the book shows that neither the language of coercion nor that of rational choice fully captures the range of situations and value systems at work in medical experiments today.When Experiments Travelchallenges conventional understandings of the ethics and politics of transnational science and changes the way we think about global medicine and the new infrastructures of our lives.
To update the international consensus on palliative radiotherapy endpoints for future clinical trials in bone metastases by surveying international experts regarding previous uncertainties within the ...2002 consensus, changes that may be necessary based on practice pattern changes and research findings since that time.
A two-phase survey was used to determine revisions and new additions to the 2002 consensus. A total of 49 experts from the American Society for Radiation Oncology, the European Society for Therapeutic Radiology and Oncology, the Faculty of Radiation Oncology of the Royal Australian and New Zealand College of Radiologists, and the Canadian Association of Radiation Oncology who are directly involved in the care of patients with bone metastases participated in this survey.
Consensus was established in areas involving response definitions, eligibility criteria for future trials, reirradiation, changes in systemic therapy, radiation techniques, parameters at follow-up, and timing of assessments.
An outline for trials in bone metastases was updated based on survey and consensus. Investigators leading trials in bone metastases are encouraged to adopt the revised guideline to promote consistent reporting. Areas for future research were identified. It is intended for the consensus to be re-examined in the future on a regular basis.