Three randomized controlled trials evaluating the impact of "spin" in health news stories reporting studies of pharmacologic treatments on patients'/caregivers' interpretation of treatment benefit.

BACKGROUND: News stories represent an important source of information. We aimed to evaluate the impact of "spin" (i.e., misrepresentation of study results) in health news stories reporting studies of pharmacologic treatments on patients'/caregivers' interpretation of treatment benefit. METHODS: We conducted three two-arm, parallel-group, Internet-based randomized trials (RCTs) comparing the interpretation of news stories reported with or without spin. Each RCT considered news stories reporting a different type of study: (1) pre-clinical study, (2) phase I/II non-RCT, and (3) phase III/IV RCT. For each type of study, we identified news stories reported with spin that had earned mention in the press. Two versions of the news stories were used: the version with spin and a version rewritten without spin. Participants were patients/caregivers involved in Inspire, a large online community of more than one million patients/caregivers. The primary outcome was participants' interpretation assessed by one specific question "What do you think is the probability that 'treatment X' would be beneficial to patients?" (scale, 0 [very unlikely] to 10 [very likely]). RESULTS: For each RCT, 300 participants were randomly assigned to assess a news story with spin (n = 150) or without spin (n = 150), and 900 participants assessed a news story. Participants were more likely to consider that the treatment would be beneficial to patients when the news story was reported with spin. The mean (SD) score for the primary outcome for abstracts reported with and without spin for pre-clinical studies was 7.5 (2.2) versus 5.8 (2.8) (mean difference [95% CI] 1.7 [1.0-2.3], p < 0.001); for phase I/II non-randomized trials, 7.6 (2.2) versus 5.8 (2.7) (mean difference 1.8 [1.0-2.5], p < 0.001); and for phase III/IV RCTs, 7.2 (2.3) versus 4.9 (2.8) (mean difference 2.3 [1.4-3.2], p < 0.001). CONCLUSIONS: Spin in health news stories reporting studies of pharmacologic treatments affects patients'/caregivers' interpretation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03094078 , NCT03094104 , NCT03095586.

Analysis of the Relationship of Cognitive Impairment and Functional Impairment in Mild Alzheimer's Disease in EXPEDITION 3.

BACKGROUND: Clinical progression of Alzheimer's disease is characterized by impairment in cognition and function. OBJECTIVE: To assess the relationship between cognitive and functional impairment in mild Alzheimer's disease. DESIGN: Spearman's rank correlations between cognitive and functional measures were calculated. Autoregressive cross-lagged panel analyses were used to determine the temporal relationship between cognitive and functional decline. SETTING: Post-hoc analysis of clinical trial data. PARTICIPANTS: Placebo-treated patients with mild Alzheimer's disease from the Phase 3 solanezumab study EXPEDITION 3. INTERVENTION: Placebo. MEASUREMENTS: Cognitive and functional measures were assessed at baseline and at six post-baseline time points through Week 80. RESULTS: Correlation between cognitive and functional measures was 0.41 at baseline and 0.65 at Week 80. Autoregressive cross-lagged panel analysis demonstrated that cognitive impairment preceded and predicted subsequent functional decline, but functional scores did not predict cognitive outcomes. CONCLUSIONS: This study supports the hypothesis that functional impairment predictably follows cognitive decline in mild Alzheimer's disease dementia.

A qualitative assessment of the experience of participating in a cancer-related clinical trial.

PURPOSE: This study aims to explore the experiences of patients enrolled in a cancer-related clinical drug treatment trial utilising a qualitative focus-group methodology. Specifically, this study aimed to explore the impact of social and family support, the challenges and advantages of taking part in a clinical trial and the experiences of patients at the conclusion of the trial. METHODS: A qualitative study was conducted at a public hospital in Melbourne in 2008. A total of 14 participants were recruited. Three focus groups and two interviews were conducted with 13 patients who had completed a cancer-related clinical trial. Comments from a letter written by a trial participant were also analysed. Interviews were audio-recorded, transcribed and coded according to emerging themes. RESULTS: Information obtained was grouped around four main themes; making sense of trial participation, challenges of treatment in the context of clinical trial participation, support during trial participation and coping with trial conclusion. Participants experienced a mixture of hope, uncertainty and apprehension as they considered whether to take part in a clinical trial. At different stages of the trial they made sense of their participation by thinking about the possible benefits of participation. Trial participation was also associated with a number of emotional and practical challenges. Generally, participants were very positive about the support they received from health professionals, family and friends. The end of the trial was associated with a mix of emotions, including relief, disappointment, hope of future help, uncertainty and abandonment. CONCLUSIONS: Clinical trial participation is a positive experience for many patients with cancer, although there are a number of associated practical and emotional challenges. Trial participants may benefit from closer follow-up from clinical trial staff, especially the treating doctor, assessment of support needs and help in re-evaluating the meaning of their trial participation if their initial hopes and expectations are not met.

Health related quality of life in NCI-sponsored cancer treatment trials.

OBJECTIVE: To highlight health related quality of life (HRQOL) measures and published outcomes in phase III clinical trials in the four major cancers: breast, prostate, colorectal, and lung. DATA SOURCES: Peer-reviewed journals, textbooks, and abstracts published between 1990 and 2009. CONCLUSION: Over the past 20 years there has been an upsurge in the number and types of HRQOL measures used in phase III cancer treatment trials. Results of trials reported after 2001 indicate a significant increase in specific treatment or disease-related symptom measures in lieu of or as companions to global HRQOL measures. Currently, open NCI-supported trials are incorporating a large number of targeted treatment- and/or disease-related measures. IMPLICATIONS FOR NURSING PRACTICE: Clinicians can use these data to help patients better understand the spectrum and severity of symptomatic toxicities they will experience with cancer treatment.

[An index of understanding randomised clinical trials in oncology]. / Index de compréhension des essais cliniques randomisés en oncologie.

The first aim of this study was to build a French validated tool (ICEC-R) assessing the objective comprehension of the modalities and purposes of participating to a randomised clinical trial (phase II or III). The second goal of the study was to compare the scores different groups of participants got at the ICEC-R in accordance with their level of expertness in this domain (physicians vs patients included in a randomised CT vs patients with standard treatment vs uninformed) and to assess whether these scores of objective comprehension were, or not, impacted by the patients' anxiety state or their satisfaction about the care they receive. The sample was composed of 474 participants, namely 73 "target patients" suffering from cancer and participating to a randomised clinical trial, 97 "standard patients" suffering from cancer but who were not included in a clinical trial, 25 "physicians" who include patients in clinical trials, 18 "caregivers" who do not include patients in clinical trials, and 261 "uninformed" (psychology students). "Target" or "standard" patients received a questionnaire composed of the randomised clinical trials comprehension inventory (ICEC-R), a trait-state anxiety scale (STAI-Y), and a scale assessing their satisfaction about the care (SAT). In addition to general information, physicians, caregivers and uninformed only completed the ICEC-R. The analyzes led us to keep a one-dimensional comprehension inventory composed of ten items which are sufficiently discriminant among the patients and for which expert physicians gave consensual answers. Finally, the patients' answers to this questionnaire seem not to be influenced by either their anxiety or their satisfaction about the care. Better evaluations of the knowledge of the patients who participate to randomised clinical trials seem to be a distinct asset to improve these patients' global clinical care.

Predicting hypothetical willingness to participate (WTP) in a future phase III HIV vaccine trial among high-risk adolescents.

The present study sought to determine whether the Theory of Planned Behaviour predicted stated hypothetical willingness to participate (WTP) in future Phase III HIV vaccine trials among South African adolescents. Hierarchical logistic regression analyses showed that The Theory of Planned Behaviour (TPB) significantly predicted WTP. Of all the predictors, Subjective norms significantly predicted WTP (OR = 1.19, 95% C.I. = 1.06-1.34). A stepwise logistic regression analysis revealed that Subjective Norms (OR = 1.19, 95% C.I. = 1.07-1.34) and Attitude towards participation in an HIV vaccine trial (OR = 1.32, 95% C.I. = 1.00-1.74) were significant predictors of WTP. The addition of Knowledge of HIV vaccines and HIV vaccine trials, Perceived self-risk of HIV infection, Health-promoting behaviours and Attitudes towards HIV/AIDS yielded non-significant results. These findings provide support for the Theory of Reasoned Action (TRA) and suggest that psychosocial factors may play an important role in WTP in Phase III HIV vaccine trials among adolescents.

Willingness to participate in HIV vaccine trials: the impact of trial attributes.

OBJECTIVES: To assess willingness to participate (WTP) in hypothetical Phase III preventive HIV vaccine trials, and the impact of trial attributes on WTP, among low socioeconomic, ethnically diverse adults from communities at elevated risk for HIV infection. METHOD: Participants (n=123; median age=38; 69% male; 37% Latino; 14% African-American) were recruited in Los Angeles in 2003 using multi-site, venue-based sampling. WTP was assessed for eight hypothetical HIV vaccine trials that varied across seven dichotomous attributes, using a 2(7-4) fractional factorial experimental design. Individual-specific impact of vaccine trial attributes on WTP was estimated using within-individual ANOVA and then meta-analyzed across individuals. RESULTS: Mean WTP for eight hypothetical vaccine trials ranged from 1.74 to 3.81 (1=highly unlikely, 5=highly likely). Lower WTP was associated with vaccine-induced infection risk (impact=0.88, p<0.0001), false HIV-positives (0.53, p<0.0001), no provision of free HIV medications (0.52, p<0.0001), and longer trial duration (0.27; p=0.0002). CONCLUSION: HIV vaccine trial attributes may strongly influence WTP. Although existing candidate vaccines cannot cause HIV infection, perceptions of risk may impede WTP. Eliciting trial preferences and concerns prior to trial implementation may enable accommodation of participant preferences and support tailored interventions to address concerns and misconceptions to facilitate enrollment in safe and ethical trials among vulnerable communities.

A pilot study to quantify parental anxiety associated with enrollment of an infant or toddler in a phase III vaccine trial.

We sought to measure the anxiety felt by parents at the time of entry into a randomized controlled vaccine trial, and to determine if anxiety level was associated with parental demographic variables or past experience. The children were 2-month-old infants entering a randomized controlled clinical trial (RCT) of a diphtheria-tetanus toxoid-acellular pertussis vaccine adsorbed with Haemophilus influenzae B conjugate, or toddlers enrolling in a RCT of a Meningococcal C conjugate vaccine. Nurses interviewed parents to collect demographic data and parents self-administered the Spielberger Self-evaluation Questionnaire (State Anxiety STAI-Y-I) [Manual for the State-Trait Anxiety Inventory (Form Y) (Self-evaluation Questionnaire), Consulting Psychologists Press Inc., Palo Alto, 1983], a validated instrument measuring the temporary condition of "state anxiety." A regression tree (CART) (S-Plus) was used to identify factors associated with higher anxiety scores. Parents of 97 children enrolled. Anxiety scores ranged from 22.75 (lower anxiety) to 36.43 (higher anxiety). The regression tree identified a structured tree with six branches. The highest anxiety scores occurred in fathers with education less then grade 8, mothers with education less than high school, birth order of the child less then the third, previous serious illness in the family, or lack of experience with research. In a group of parents agreeing to enroll their infant or toddler in a vaccine study, certain attributes and experiences were associated with higher anxiety at the time of immunization in the context of a RCT. These factors should be considered by vaccine researchers in the recruitment process of clinical trials.

Willingness to volunteer in future preventive HIV vaccine trials: issues and perspectives from three U.S. communities.

UNLABELLED: This study examined perceived risks, benefits, and desired information related to willingness to volunteer in preventive HIV vaccine trials. SAMPLE: Purposive sampling was used to select 90 participants among injecting drug users (Philadelphia, PA, U.S.A.); gay men (San Francisco, CA, U.S.A.); and black Americans (Durham, NC, U.S.A.). METHODS: A qualitative interview guide elicited perceived benefits, risks, and desired information relating to trial participation. Themes were developed from the transcribed texts and from freelists. RESULTS: Stated willingness to volunteer in a preventive HIV vaccine trial was similar across the three communities. Eight perceived benefits were reported, including self-benefits, altruism, and stopping the spread of AIDS. Seven perceived risks were reported, including negative side effects and vaccine safety issues, contracting HIV from the vaccine, and social stigmatization. Participants voiced the desire for eight types of information about issues relating to trust and confidentiality in the research process, health complications and later assistance, and vaccine trial methodology. CONCLUSIONS: In this study, many benefits as well as risks of preventive HIV vaccine trial participation were cited. Scientists conducting preventive HIV vaccine trials need to address community perceptions of risks and provide information about the research if trial enrollment is to be diverse and successful.

Challenges posed by non-random missing quality of life data in an advanced-stage colorectal cancer clinical trial.

Effects of variations in agent, dose, and route of treatment administration on patient reported quality of life (QOL) were examined for 279 patients enrolled on a seven-arm randomized clinical trial (S8905) of 5-FU and its modulation for advanced colorectal cancer. Patients completed QOL questionnaires at randomization and weeks 6, 11, and 21 post-randomization with five QOL endpoints considered primary: three treatment-specific symptoms (stomatitis, diarrhea, and hand/foot sensitivity); physical functioning; and emotional functioning. Patient compliance with the QOL assessment schedule was good, supporting the feasibility of including QOL measures in cooperative group trials. However, death and deteriorating health produced substantial missing data. Cross-sectional analyses indicated that the seven therapeutic arms did not differ in their impact on QOL. Unfortunately, longitudinal analyses of the QOL data were inappropriate given non-random missing data. Graphical presentation of non-random missing data identified the seriousness of this problem and its effect on potential conclusions about QOL during treatment. This problem appears to be particularly challenging in the context of advanced-stage disease. Failure to recognize the presence of non-random missing data can lead to serious overestimates of patient QOL over time.

Decision-making process in patients before entering phase III cancer clinical trials: a pilot study.

The present study was performed to gain insight into the decision-making process that patients go through when asked to participate in a cancer clinical trial. Fourteen cancer patients entered a pilot study concerning decision making. They were interviewed in a semistructured manner after consenting or refusing to participate in a randomized phase III clinical trial concerning chemotherapy or immunotherapy. Results from this study showed that patients, after receiving information from the medical oncologist, oncology nurse, or both, decide about participation instantaneously. This means that time for procedural soundness has not been used, which raises questions about the normative quality of the decision.

Willingness to participate in HIV-1 vaccine efficacy trials and the effect of media events among gay and bisexual men in New York City: Project ACHIEVE.

Efficacy trials of candidate HIV-1 vaccines require study populations at high risk of infection who adhere to study protocols and who are willing to participate. Data from HIV-1 antibody-negative men (n = 698) enrolled in Project ACHIEVE in New York City were analyzed to assess willingness to participate in efficacy trials, factors influencing willingness, and the effect on willingness of the June 1994 media events about the decision not to proceed with phase III trials and about breakthrough infections during phase I and II vaccine trials. Sixty-eight percent indicated they would definitely or probably be willing to participate. Men enrolled during the time of media events were significantly less willing compared with men enrolled during other periods. These men were also more likely to mention safety of the vaccine, fear or mistrust of research or government, and social risks as important factors in their decision compared with men enrolled during other periods. The most frequently cited motivator for participation was altruism (57%); the most frequently cited barriers were vaccine safety (36%) and vaccine-induced seropositivity (19%). A substantial proportion of this cohort was willing to participate in future vaccine efficacy trials. However, because willingness may be affected by issues of vaccine safety, vaccine-induced seropositivity, and media coverage of these issues, significant efforts are needed for participant and community education, and specific concerns must be addressed in the design and implementation of trials.

Telephone-based nursing intervention improves the effectiveness of the informed consent process in cancer clinical trials.

PURPOSE: Here we report the results of a randomized study undertaken to test the efficacy of a supplementary, telephone-based nursing intervention in increasing patients' awareness and understanding of the clinical trials in which they are asked to participate. METHODS: During a 12-month period, 180 cancer patients who were approached to participate in a phase II or III clinical trial were randomized to undergo either of the following: (1) standard informed consent procedures based on verbal explanations from the treating physician plus written information (controls); or (2) standard informed consent procedures plus a supplementary, telephone-based contact with an oncology nurse (intervention). For purposes of evaluation, face-to-face interviews were conducted with all patients approximately 1 week after the informed consent process had been completed. RESULTS: The two groups were comparable with regard to sociodemographic and clinical variables. Both groups had a high level of awareness of the diagnosis and of the nature and objectives of the proposed treatments. The intervention group was significantly (P < .01) better informed about the following: (1) the risks and side effects of treatment; (2) the clinical trial context of the treatment; (3) the objectives of the clinical trial; (4) where relevant, the use of randomization in allocating treatment; (5) the availability of alternative treatments; (6) the voluntary nature of participation; and (7) the right to withdraw from the clinical trial. The intervention did not have any significant effect on patients' anxiety levels or on rates of clinical trial participation. Patients reported high levels of satisfaction with the intervention. CONCLUSION: The use of a supplementary, telephone-based nursing intervention is a feasible and effective means to increase cancer patients' awareness and understanding of the salient issues that surround the clinical trials in which they are asked to participate.