Patient motivations surrounding participation in phase I and phase II clinical trials of cancer chemotherapy.
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ABSTRACT:
SUBMITTER: Nurgat ZA
PROVIDER: S-EPMC2361930 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Between-patient heterogeneity is very common in clinical trials. This complicates treatment evaluation, due to known prognostic subgroup effects or potential treatment-subgroup interactions. We review two Bayesian phase II clinical trial designs that account explicitly for patient heterogeneity. The first design uses analysis of covariance to assess treatment effects in subgroups known to have different prognoses. The second design uses a hierarchical model for settings where, a priori, the experimental treatment effects in the subgroups are assumed to be exchangeable.Compared with simpler designs that ignore patient heterogeneity, each design provides substantial improvements by reducing both false positive and false negative rates and focusing resources on subgroups where an experimental treatment is more likely to provide an advance over standard therapy. In either case, accounting for potential treatment-subgroup interactions is extremely important.Due to the rapidly increasing number of potential new treatments to be evaluated clinically, increasing costs and limited resources, it is critically important to perform early phase clinical trials efficiently. The new Bayesian methods described here and other related methods provide efficient, broadly applicable tools to address these problems.
| S-EPMC5555403 | biostudies-other
Project description:BACKGROUND:Clinical treatment trials are increasingly being designed in primary mitochondrial disease (PMD), a phenotypically and genetically heterogeneous collection of inherited multi- system energy deficiency disorders that lack effective therapy. We sought to identify motivating factors and barriers to clinical trial participation in PMD. METHODS:A survey study was conducted in two independent mitochondrial disease subject cohorts. A discovery cohort invited subjects with well-defined biochemical or molecularly- confirmed PMD followed at a single medical center (CHOP, n = 30/67 (45%) respondents). A replication cohort included self-identified PMD subjects in the Rare Disease Clinical Research Network (RDCRN) national contact registry (n = 290/1119 (26%) respondents). Five-point Likert scale responses were analyzed using descriptive and quantitative statistics. Experienced and prioritized symptoms for trial participation, and patient attitudes toward detailed aspects of clinical trial drug features and study design. RESULTS:PMD subjects experienced an average of 16 symptoms. Muscle weakness, chronic fatigue, and exercise intolerance were the lead symptoms encouraging trial participation. Motivating trial design factors included a self-administered study drug; vitamin, antioxidant, natural or plant-derivative; pills; daily treatment; guaranteed treatment access during and after study; short travel distances; and late-stage (phase 3) participation. Relative trial participation barriers included a new study drug; discontinuation of current medications; disease progression; daily phlebotomy; and requiring participant payment. Treatment trial type or design preferences were not influenced by population age (pediatric versus adult), prior research trial experience, or disease severity. CONCLUSIONS:These data are the first to convey clear PMD subject preferences and priorities to enable improved clinical treatment trial design that cuts across the complex diversity of disease. Partnering with rare disease patient communities is essential to effectively design robust clinical trials that engage patients and enable meaningful evaluation of emerging treatment interventions.
| S-EPMC5957366 | biostudies-literature
Project description:Phase II cancer clinical trial designs commonly incorporate an interim analysis for lack of efficacy. To strictly and ethically implement such designs, one should suspend accrual in cases where pending patient outcomes can affect early termination decisions. This article aims to evaluate various options for accrual suspension and illustrate how the suspension strategy affects operating characteristics of the trial.We define a strict suspension strategy for determining whether one should continue, suspend, or restart accrual at any point within the trial. The strategy is compared to a naive implementation of suspension and a strategy of no suspension. We evaluate the methods' operating characteristics by simulation.The suspension strategy has little effect on type I error, power, and early termination probability. Methods that involve stricter suspension policies generally lead to smaller but longer trials. Differences across strategies are substantial when the ratio of enrollment rate to outcome availability rate is high.The suspension strategy is most relevant in trials that accrue rapidly and require lengthy observation of each subject. The choice of suspension strategy involves a tradeoff between the cost of implementing a potentially complex suspension algorithm in real time versus the cost of enrolling more patients and exposing them to a potentially toxic and ineffective treatment regimen.
| S-EPMC4355337 | biostudies-literature
Project description:A phase II trial is conducted to investigate if an experimental therapy is efficacious enough to proceed to a large-scale phase III trial or not. In spite of the fast progress in design and analysis methods, single-arm two-stage design is still the most popular for phase II cancer clinical trials. In this review article, we discuss two design and analysis methods that are popularly used for phase II clinical trials, but that can cause serious bias. One is about using the sample proportion as the estimator of the true response rate from single-arm two-stage trials. For a two-stage design with a futility interim test, the sample proportion is negatively biased by ignoring the two-stage design. The other is about the design and analysis of single-arm phase II trials for patient populations consisting of multiple sub-populations with different response rates. In this case, a standard design method is to project the prevalence of each subpopulation and select a standard two-stage design based on the expected response rate for the whole population. By using an unstratified statistical testing in this case, the standard analysis method can be seriously biased if the observed prevalence is very different from the projected one. In this paper, we review appropriate design and analysis methods that are proposed to avoid these sources of bias.
| S-EPMC9577758 | biostudies-literature
Project description:ObjectivesIf patients are to reap the benefits of continued drug development, an understanding of why healthy participants take part in phase I clinical trials is imperative. The current study aimed to explore the nature of these underlying motivations which may, in turn, improve the overall participant experience and assist in the development of more effective recruitment and retention strategies.DesignThis study used a qualitative design based on the theory of planned behaviour. Specifically, it explored healthy participants' underlying behavioural, control and normative beliefs which influence their participation in phase I clinical trials.SettingThis study took place at a company that specialises in conducting phase I and phase II clinical trials in the Australian state of Queensland.ParticipantsParticipants (n=31) were either currently undergoing a phase I clinical trial or had previously taken part in a phase I clinical trial.ResultsResults showed that the motivations were varied and not solely centred on financial gains. Reported advantages of participation included altruism, while inconvenience was most often reported as a disadvantage. Friends were reported as those most likely to approve, while one's mother was reported as most likely to disapprove. Having a suitable time frame/flexible scheduling and feeling comfortable taking part in the trial were both the most commonly reported facilitators, while inflexible scheduling/time commitment was the most commonly reported barrier.ConclusionsPractical implications included the need for organisations involved in clinical trials to be mindful of inflexible scheduling and exploring the possibility of making educational materials available to family members who may be concerned about the risks associated with participation. Overall, it is anticipated that the results of this study will improve the understanding of factors that influence phase I clinical trial participation which may, ultimately, help develop new therapeutics to improve patient health.
| S-EPMC6340482 | biostudies-literature
Project description:IntroductionProspective clinical trials are essential to translate new therapy concepts or rather any scientific development into the medical routine. Besides a sophisticated trial protocol, the success of clinical trials depends on patient recruitment and participation. Patient recruitment remains a challenge and depends on several factors. To get a current picture of the patients' attitude, we conducted the present survey.MethodsWe designed a survey with seven questions, which was given to all oncological patients treated within a timeframe of three months between Mai and July 2017. Participation was voluntary and anonymous. The questionnaire mainly inquires patients' participation in clinical trials in a university-based setting, their attitude towards clinical trials regarding risks and benefits, and their source of information in this context.Results771 patients (1:1 male/female) participated with a median age of 61 years (range 18-91 years) with a response rate of 71.5%. Of all, 17.8% (137/771) were participating in a clinical trial. The most mentioned reason was to serve medical progress and cancer research. Out of the patients not currently participating in a trial, 79 (12.7%, 79/623) refusers named the following main reasons: extensive travel time to the clinic, no therapeutic advantage, and too time-consuming. Out of the patients not offered to take part in a trial, 265 (51.0%, 265/520) would participate if offered. Of all patients, 8.3% (64/771) used the clinics' homepage as a source of information, of those 79.7% (51/64) were satisfied with its content. To enhance patient recruitment strategies, we asked how patients wish to be informed about possible trials: More than half (52.0%) of the questioned patients preferred an individual medical consultation with their physician.We further analyzed the trial participation depending on age, gender, unit, and tumor entity. We could show a significant influence of age (p < 0.001) but not for gender (p = 0.724). The trial participation was also significantly associated with the treating unit (p < 0.001) and tumor entity (p = 0.001).ConclusionPatients are willing to participate in clinical trials. Better information strategies need to be implemented. Physicians need to be aware of running trials within their department and must counseling counsel patients effectively to improve recruitment. Trial concepts should keep in mind patients' needs including an adequate number of appointments, positive risk-benefit profiles, and information material.
| S-EPMC6192009 | biostudies-literature
Project description:BackgroundWe report on the results of a phase II clinical trial of Panagen (tablet form of fragmented human DNA preparation) in breast cancer patients (placebo group n = 23, Panagen n = 57). Panagen was administered as an adjuvant leukoprotective agent in FAC and AC chemotherapy regimens. Pre-clinical studies clearly indicate that Panagen acts by activating dendritic cells and induces the development of adaptive anticancer immune response.MethodsWe analyzed 5-year disease-free survival of patients recruited into the trial.ResultsFive-year disease-free survival in the placebo group was 40 % (n = 15), compared with the Panagen arm - 53 % (n = 51). Among stage III patients, disease-free survival was 25 and 52 % for placebo (n = 8) and Panagen (n = 25) groups, respectively. Disease-free survival of patients with IIIB + C stage was as follows: placebo (n = 6)-17 % vs Panagen (n = 18)-50 %.ConclusionsDisease-free survival rate (17 %) of patients with IIIB + C stage breast cancer receiving standard of care therapy is within the global range. Patients who additionally received Panagen demonstrate a significantly improved disease-free survival rate of 50 %. This confirms anticancer activity of Panagen.Trial registrationClinicalTrials.gov NCT02115984 from 04/07/2014.
| S-EPMC4990870 | biostudies-literature
Project description:BackgroundPatients with advanced cancer who no longer have standard treatment options available may decide to participate in early phase clinical trials (i.e. experimental treatments with uncertain outcomes). Shared decision-making (SDM) models help to understand considerations that influence patients' decision. Discussion of patient values is essential to SDM, but such communication is often limited in this context and may require new interventions. The OnVaCT intervention, consisting of a preparatory online value clarification tool (OnVaCT) for patients and communication training for oncologists, was previously developed to support SDM. This study aimed to qualitatively explore associations between patient values that are discussed between patients and oncologists during consultations about potential participation in early phase clinical trials before and after implementation of the OnVaCT intervention.MethodsThis study is part of a prospective multicentre nonrandomized controlled clinical trial and had a between-subjects design: pre-intervention patients received usual care, while post-intervention patients additionally received the OnVaCT. Oncologists participated in the communication training between study phases. Patients' initial consultation on potential early phase clinical trial participation was recorded and transcribed verbatim. Applying a directed approach, two independent coders analysed the transcripts using an initial codebook based on previous studies. Steps of continuous evaluation and revision were repeated until data saturation was reached.ResultsData saturation was reached after 32 patient-oncologist consultations (i.e. 17 pre-intervention and 15 post-intervention). The analysis revealed the values: hope, perseverance, quality or quantity of life, risk tolerance, trust in the healthcare system/professionals, autonomy, social adherence, altruism, corporeality, acceptance of one's fate, and humanity. Patients in the pre-intervention phase tended to express values briefly and spontaneously. Oncologists acknowledged the importance of patients' values, but generally only gave 'contrasting' examples of why some accept and others refuse to participate in trials. In the post-intervention phase, many oncologists referred to the OnVaCT and/or asked follow-up questions, while patients used longer phrases that combined multiple values, sometimes clearly indicating their weighing.ConclusionsWhile all values were recognized in both study phases, our results have highlighted the different communication patterns around patient values in SDM for potential early phase clinical trial participation before and after implementation of the OnVaCT intervention. This study therefore provides a first (qualitative) indication that the OnVaCT intervention may support patients and oncologists in discussing their values.Trial registrationNetherlands Trial Registry: NL7335, registered on July 17, 2018.
| S-EPMC10835819 | biostudies-literature
Project description:ObjectiveThe participation of patients with advanced cancer(s) in clinical trials is vital for new drug development. We aimed to investigate patients' decision-making processes and satisfaction with their decision (SWD) to participate; the study's purpose was to provide results that can help support high-quality research in clinical trials. In addition, we explored how shared decision-making (SDM) mediates the relationship between understanding informed consent forms and SWD to participate in a clinical trial.MethodsA cross-sectional study was conducted. A purposive sample of 111 cancer patients was recruited, and they completed a questionnaire on demographic characteristics, SDM, and decision-making satisfaction to participate in a clinical trial. Correlation and mediation analyses were used.ResultsParticipants aged under 65 years and with higher education reported high SWDs, and SDM significantly mediated the relationship between self-assessed understanding of informed consent forms and SWDs related to clinical trials.ConclusionsSDM in patients with lung or liver cancer was a significant mediator between understanding the informed consent form and the patient's SWD. The higher the SWD level of participating in clinical trials, the better study team members' SDM involvement and the better the comprehension of informed consent forms. In addition, patients' age and education level should also be considered as influencing factors in SWD. This survey is the first in Taiwan to examine SDM in drug-related clinical trials. The study results provide evidence to support SDM in a clinical trial model and develop informed consent process policies in research facilities.
| S-EPMC10372169 | biostudies-literature
Project description:PurposeStudies have shown an association between socioeconomic status (SES) and quality of oncology care, but less is known about the impact of patient SES on clinical trial participation.Patients and methodsWe assessed clinical trial participation patterns according to important SES (income, education) and demographic factors in a large sample of patients surveyed via an Internet-based treatment decision tool. Logistic regression, conditioning on type of cancer, was used. Attitudes toward clinical trials were assessed using prespecified items about treatment, treatment tolerability, convenience, and cost.ResultsFrom 2007 to 2011, 5,499 patients were successfully surveyed. Forty percent discussed clinical trials with their physician, 45% of discussions led to physician offers of clinical trial participation, and 51% of offers led to clinical trial participation. The overall clinical trial participation rate was 9%. In univariate models, older patients (P = .002) and patients with lower income (P = .001) and education (P = .02) were less likely to participate in clinical trials. In a multivariable model, income remained a statistically significant predictor of clinical trial participation (odds ratio, 0.73; 95% CI, 0.57 to 0.94; P = .01). Even in patients age ≥ 65 years, who have universal access to Medicare, lower income predicted lower trial participation. Cost concerns were much more evident among lower-income patients (P < .001).ConclusionLower-income patients were less likely to participate in clinical trials, even when considering age group. A better understanding of why income is a barrier may help identify ways to make clinical trials better available to all patients and would increase the generalizability of clinical trial results across all income levels.
| S-EPMC3565180 | biostudies-literature