Patient Perceptions in a Nonblinded Randomized Trial of Radiation Therapy Technologies: A Novel Survey Study Exploring Therapeutic Misconception.

PURPOSE: Therapeutic misconception is the tendency for a clinical trial participant to overlook the scientific objective of a clinical trial and instead believe that an experimental intervention is intended for personal therapeutic benefit. We sought to evaluate this tendency in the setting of a clinical trial of a new radiation therapy technology. METHODS: Patients with left-sided, node positive breast cancer enrolled in a randomized clinical trial evaluating intensity modulated radiation therapy with deep inspiration breath hold (IMRT-DIBH) versus 3-dimensional conformal radiation therapy (3DCRT). Patients who enrolled completed surveys at baseline, after randomization, and upon completion of radiation therapy to evaluate expectations, satisfaction, and experiences. RESULTS: Forty women participated in the survey study, with 20 in each arm. Most participants endorsed the perception that participation in the trial might result in better treatment than the current standard treatment (77%) and more medical attention than being off trial (54%). At baseline, most women (74%) believed that a new treatment technology is superior than an established one. Before randomization, 43% of participants believed IMRT-DIBH would be more effective than standard treatment with 3DCRT, none believed that 3DCRT would be more effective, 23% believed that they would be the same, and 34% did not know. None believed that IMRT-DIBH would cause worse long-term side effects, whereas 37% thought that 3DCRT would. Most (71%) reported that they would choose to be treated with IMRT-DIBH; none would have elected 3DCRT if given a choice. Nearly half (44%) in the 3DCRT arm wished that they had been assigned to the IMRT-DIBH arm; none in the IMRT-DIBH arm expressed a wish for crossover. CONCLUSIONS: Most participants reported the perception that trial participation would result in better treatment and more medical attention than off trial, hallmarks of therapeutic misconception. Our observations provide empirical evidence of a fixed belief in the superiority of new technology and highlight the importance of adjusting expectations through informed consent to mitigate therapeutic misconception.

Investigation of the effects of treatment planning variables in small animal radiotherapy dose distributions.

PURPOSE: Methods used for small animal radiation treatment have yet to achieve the same dose targeting as in clinical radiation therapy. Toward understanding how to better plan small animal radiation using a system recently developed for this purpose, the authors characterized dose distributions produced from conformal radiotherapy of small animals in a microCT scanner equipped with a variable-aperture collimator. METHODS: Dose distributions delivered to a cylindrical solid water phantom were simulated using a Monte Carlo algorithm. Phase-space files for 120 kVp x-ray beams and collimator widths of 1-10 mm at isocenter were generated using BEAMnrc software, and dose distributions for evenly spaced beams numbered from 5 to 80 were generated in DOSXYZnrc for a variety of targets, including centered spherical targets in a range of sizes, spherical targets offset from centered by various distances, and various ellipsoidal targets. Dose distributions were analyzed using dose volume histograms. The dose delivered to a mouse bearing a spontaneous lung tumor was also simulated, and dose volume histograms were generated for the tumor, heart, left lung, right lung, and spinal cord. RESULTS: Results indicated that for centered, symmetric targets, the number of beams required to achieve a smooth dose volume histogram decreased with increased target size. Dose distributions for noncentered, symmetric targets did not exhibit any significant loss of conformality with increasing offset from the phantom center, indicating sufficient beam penetration through the phantom for targeting superficial targets from all angles. Even with variable collimator widths, targeting of asymmetric targets was found to have less conformality than that of spherical targets. Irradiation of a mouse lung tumor with multiple beam widths was found to effectively deliver dose to the tumor volume while minimizing dose to other critical structures. CONCLUSIONS: Overall, this method of generating and analyzing dose distributions provides a quantitative method for developing practical guidelines for small animal radiotherapy treatment planning. Future work should address methods to improve conformality in asymmetric targets.

Sex differences in attainment of independent funding by career development awardees.

BACKGROUND: Concerns have been raised about the career pipeline in academic medicine, including whether women with a demonstrated commitment to research succeed at the same rate as male colleagues. OBJECTIVE: To determine the subsequent academic success of recipients of National Institutes of Health (NIH) career development awards. SETTING: United States. PARTICIPANTS: 2784 of 2799 (99.5%) recipients of K08 and K23 awards for whom sex could be ascertained from the NIH Computer Retrieval of Information on Scientific Projects database and other publicly available sources. MEASUREMENTS: Actuarial rates at which recipients of K08 and K23 awards from 1997 to 2003 went on to receive R01 awards. Sex-specific rates of R01 award attainment were calculated by using the Kaplan-Meier method, and sex differences were assessed by using a Cox proportional hazards model. RESULTS: Overall, 31.4% of the 1919 K08 awardees and 43.7% of the 865 K23 awardees were female (P < 0.001). Women were less likely than men to receive an R01 award (P < 0.001). The actuarial rate of R01 award attainment at 5 years was 22.7% overall, 18.8% among women, and 24.8% among men. At 10 years, the rate was 42.5% overall, 36.2% among women, and 45.6% among men. Sex persisted as an independent significant predictor of R01 award attainment (hazard ratio, 0.79 [95% CI, 0.68 to 0.92]; P = 0.002) in multivariate analysis controlling for K award type, year of award, funding institute, institution, and specialty. LIMITATION: Whether the lower rate of R01 award achievement among women is due to lower rates of application or lower rates of success in application could not be determined. CONCLUSION: Only a minority of K awardees studied achieved R01 award funding during the period assessed, and a significant sex disparity was evident.

Under-representation of women in high-impact published clinical cancer research.

BACKGROUND: Adequate representation of women in research has been deemed essential. METHODS: Cancer research published in 8 journals in 2006 was reviewed. The percentage of women among study participants was compared with the proportion expected from population-based estimates of sex-specific cancer incidence, using binomial tests. Differences were assessed in sex distribution of participants by funding source, author sex, and focus of research with the Student t test, and in a linear regression model controlling for cancer type. RESULTS: A total of 1534 cancer research articles were identified, of which 661 (representing 1,096,098 participants) were prospective clinical studies and were analyzed further. For all 7 non-sex-specific cancer types assessed, the majority of studies analyzed included a lower proportion of women than the proportion of women among patients having cancer of that type in the general population. Among studies focusing on cancer treatment, women constituted a significantly lower overall proportion of the participants in the analyzed studies than expected for 6 of 7 non-sex-specific cancer types (P < .001). Among non-sex-specific studies, the mean percentage of participants who were women was 38.8%. Non-sex-specific studies reporting government funding had a higher percentage of female participants (mean 41.3% vs 36.9%; P = .005). In a regression model controlling for cancer type, lack of government funding (P = .03) and focus on cancer treatment (P = .03) were found to be independent significant predictors of a lower percentage of female participants. CONCLUSIONS: Women were under-represented as participants in recently published, high-impact studies of non-sex-specific cancers. Studies that received government funding included a higher proportion of female subjects.

Frequency, nature, effects, and correlates of conflicts of interest in published clinical cancer research.

BACKGROUND: Relationships between clinical researchers and industry are becoming increasingly complex. The frequency and impact of conflicts of interest in the full range of high-impact, published clinical cancer research is unknown. METHODS: The authors reviewed cancer research published in 8 journals in 2006 to determine frequency of self-reported conflicts of interest, source of study funding, and other characteristics. They assessed associations between the likelihood of conflicts of interest and other characteristics by using chi-squared testing. They also compared the likelihood of positive outcome in randomized trials with and without conflicts of interest by chi-squared testing. RESULTS: The authors identified 1534 original oncology studies; 29% had conflicts of interest (including industrial funding) and 17% declared industrial funding. Conflicts of interest varied by discipline (P < .001), continental origin (P < .001), and sex (P < .001) of the corresponding author and were most likely in articles with corresponding authors from departments of medical oncology (45%), those from North America (33%), and those with male first and senior authors (37%). Frequency of conflicts also varied considerably depending upon disease site studied. Studies with industrial funding were more likely to focus on treatment (62% vs 36%; P < .001), and randomized trials that assessed survival were more likely to report positive survival outcomes when a conflict of interest was present (P = .04). CONCLUSIONS: Conflicts of interest characterize a substantial minority of clinical cancer research published in high-impact journals. Therefore, attempts to disentangle the cancer research effort from industry merit further attention, and journals should embrace both rigorous standards of disclosure and heightened scrutiny when conflicts exist.