Tolerating bad health research: the continuing scandal

BackgroundAt the 2015 REWARD/EQUATOR conference on research waste, the late Doug Altman revealed that his only regret about his 1994 BMJ paper ‘The scandal of poor medical research’ was that he used the word ‘poor’ rather than ‘bad’. But how much research is bad? And what would improve things?Main textWe focus on randomised trials and look at scale, participants and cost. We randomly selected up to two quantitative intervention reviews published by all clinical Cochrane Review Groups between May 2020 and April 2021. Data including risk of bias, number of participants, intervention type and country were extracted for all trials included in selected reviews. High risk of bias trials were classed as bad. The cost of high risk of bias trials was estimated using published estimates of trial cost per-participant.We identified 96 reviews authored by 546 reviewers from 49 clinical Cochrane Review Groups that included 1,659 trials done in 84 countries. Of the 1,640 trials providing risk of bias information, 1,013 (62%) were high risk of bias (bad), 494 (30%) unclear and 133 (8%) low risk of bias. Bad trials were spread across all clinical areas and all countries. Well over 220,000 participants (or 56% of all participants) were in bad trials. The low estimate of the cost of bad trials was £726 million; our high estimate was over £8 billion. We have five recommendations: trials should be neither funded (1) or given ethical approval (2) unless they have a statistician and methodologist; trialists should use a risk of bias tool at design (3); more statisticians and methodologists should be trained and supported (4); there should be more funding into applied methodology research and infrastructure (5). ConclusionsMost randomised trials are bad and most trial participants will be in one. The research community has tolerated this for decades. This has to stop: we need to put rigour and methodology where it belongs– at the centre of our science.

Leveraging Blockchain Technology for Informed Consent Process and Patient Engagement in a Clinical Trial Pilot

Objective: Despite the implementation of quality assurance procedures, current clinical trial management processes are time-consuming, costly, and often susceptible to error. This can result in limited trust, transparency, and process inefficiencies, without true patient empowerment. The objective of this study was to determine whether blockchain technology could enforce trust, transparency, and patient empowerment in the clinical trial data management process, while reducing trial cost. Design: In this proof of concept pilot, we deployed a Hyperledger Fabric-based blockchain system in an active clinical trial setting to assess the impact of blockchain technology on mean monitoring visit time and cost, non-compliances, and user experience. Using a parallel study design, we compared differences between blockchain technology and standard methodology. Results: A total of 12 trial participants, seven study coordinators and three clinical research associates across five sites participated in the pilot. Blockchain technology significantly reduces total mean monitoring visit time and cost versus standard trial management (475 to 7 min; P = 0.001; €722 to €10; P = 0.001 per participant/visit, respectively), while enhancing patient trust, transparency, and empowerment in 91, 82 and 63% of the patients, respectively. No difference in non-compliances as a marker of trial quality was detected. Conclusion: Blockchain technology holds promise to improve patient-centricity and to reduce trial cost compared to conventional clinical trial management. The ability of this technology to improve trial quality warrants further investigation.

Financial toxicity, symptom burden, illness perceptions, and communication confidence in cancer clinical trial participants.

86 Background: Cancer clinical trial (CCT) participants are at risk for experiencing adverse effects from financial toxicity, yet these remain understudied. We sought to describe associations among CCT participant-reported financial toxicity (financial burden [FB] and trial cost concerns), symptoms, illness perceptions, communication confidence, hospitalizations, and survival. Methods: From 7/2015-7/2017, we prospectively enrolled CCT participants who expressed interest in financial assistance (n = 100) and a patient group matched by age, sex, cancer type, specific trial, and trial phase (n = 98). We assessed FB (burdened by costs of cancer care), trial cost concerns (worried about affording medical costs of a CCT), physical (Edmonton Symptom Assessment Scale [ESAS]) and psychological (Patient Health Questionnaire-4 [PHQ-4]) symptoms, illness perceptions (Brief Illness Perception Questionnaire [BIPQ]), and communication confidence (Perceived Efficacy in Patient-Physician Interactions [PEPPI]). We used regression models to explore sociodemographic associations with FB and trial cost concerns, as well as their associations with symptom burden, illness perceptions, and communication confidence, adjusting for age, sex, race, performance status, marital status, and metastatic status. We also used Kaplan-Meier and regression methods to evaluate their associations with 6-month hospitalizations and survival. Results: Of 198 patients enrolled, 112 (56.6%) reported FB and 82 (41.4%) had trial cost concerns. Patients with FB were younger (OR 0.96, 95% CI 0.94-0.98) with lower incomes (< $100,000, OR 4.61, 95% CI 2.35-9.01). Patients with trial cost concerns had lower incomes (< $100,000, OR 2.78, 95% CI 1.45-5.29). On adjusted analyses, patients with FB had higher ESAS (OR 1.03, 95% CI 1.02-1.05), PHQ-4 depression (OR 1.54, 95% CI 1.22-1.94), and PHQ-4 anxiety (OR 1.30, 95% CI 1.08-1.55) scores, as well as more negative illness perceptions (OR 1.04, 95% CI 1.01-1.07), but no significant difference in communication confidence (OR 0.98, 95% CI 0.93-1.05). Patients reporting trial cost concerns had higher ESAS (OR 1.03, 95% CI 1.01-1.05), PHQ-4 depression (OR 1.35, 95% CI 1.10-1.65), and PHQ-4 anxiety (OR 1.27, 95% CI 1.07-1.51) scores, as well as more negative illness perceptions (OR 1.06, 95% CI 1.03-1.10), and lower communication confidence (OR 0.93, 95% CI 0.87-0.99). Financial toxicity was not significantly associated with hospitalizations or survival. Conclusions: In this study of CCT participants, younger patients with lower incomes were most vulnerable to financial toxicity. Financial toxicity was associated with greater symptoms, more negative illness perceptions, and lower communication confidence, underscoring the importance of addressing these issues when seeking to alleviate the adverse effects of financial toxicity in CCT participants.

Financial toxicity, symptom burden, illness perceptions, and communication confidence in cancer clinical trial participants.

6526 Background: Cancer clinical trial (CCT) participants are at high risk for experiencing adverse effects from financial toxicity, yet this remains understudied in the CCT population. We sought to describe associations among patient-reported financial toxicity (financial burden [FB] and trial cost concerns), physical and psychological symptoms, illness perceptions, and communication confidence in CCT participants. Methods: From 7/2015-7/2017, we prospectively enrolled CCT participants who expressed interest in financial assistance and a group of patients matched by age, sex, cancer type, specific trial, and trial phase. We assessed FB (burdened by costs of cancer care), trial cost concerns (worried about affording medical costs of a CCT), physical (Edmonton Symptom Assessment Scale [ESAS]) and psychological (Patient Health Questionnaire-4 [PHQ-4]) symptoms, illness perceptions (Brief Illness Perception Questionnaire [BIPQ]), and communication confidence (Perceived Efficacy in Patient-Physician Interactions [PEPPI]). We used regression models to explore sociodemographic associations with FB and trial cost concerns, and to examine associations of FB and trial cost concerns with patients’ symptom burden, illness perceptions, and communication confidence, adjusting for age, sex, race, performance status, marital status, and metastatic status. Results: Of 198 patients enrolled, 112 (56.6%) reported FB and 82 (41.4%) had trial cost concerns. Patients with FB were younger (OR 0.96, 95% CI 0.94-0.98) and had lower incomes ( < $100,000, OR 4.61, 95% CI 2.35-9.01). Patients reporting trial cost concerns also had lower incomes ( < $100,000, OR 2.78, 95% CI 1.45-5.29). On adjusted analyses, patients with FB had higher ESAS total (OR 1.03, 95% CI 1.02-1.05), ESAS physical (OR 1.04, 95% CI 1.02-1.07), PHQ-4 depression (OR 1.54, 95% CI 1.22-1.94), and PHQ-4 anxiety (OR 1.30, 95% CI 1.08-1.55) scores, as well as more negative illness perceptions (OR 1.04, 95% CI 1.01-1.07), but no significant difference in communication confidence (OR 0.98, 95% CI 0.93-1.05). Patients reporting trial cost concerns had higher ESAS total (OR 1.03, 95% CI 1.01-1.05), ESAS physical (OR 1.04, 95% CI 1.01-1.06), PHQ-4 depression (OR 1.35, 95% CI 1.10-1.65), and PHQ-4 anxiety (OR 1.27, 95% CI 1.07-1.51) scores, as well as more negative illness perceptions (OR 1.06, 95% CI 1.03-1.10), and lower communication confidence (OR 0.93, 95% CI 0.87-0.99). Conclusions: In this study of CCT participants, younger patients with lower incomes were most vulnerable to financial toxicity. Financial toxicity was associated with greater symptom burden, more negative illness perceptions, and lower communication confidence, which underscores the importance of addressing these issues when seeking to alleviate the adverse effects of financial toxicity in CCT participants.

OP272 Two-Year Within-Trial And Estimated Lifetime Cost Effectiveness Of The Weight Management Program In The Diabetes REmission Clinical Trial (DiRECT)

IntroductionType 2 diabetes results mainly from weight gain in adult life and affects one in twelve people worldwide. In the Diabetes REmission Clinical Trial (DiRECT), the primary care-led Counterweight-Plus weight management program achieved remission of type 2 diabetes (for up to six years) for forty-six percent of patients after one year and thirty-six percent after two years. The objective of this study was to estimate the implementation costs of the program, as well as its two-year within-trial cost effectiveness and lifetime cost effectiveness.MethodsWithin-trial cost effectiveness included the Counterweight-Plus costs (including training, practitioner appointments, and low-energy diet), medications, and all routine healthcare contacts, combined with achieved remission rates. Lifetime cost per quality-adjusted life-year (QALY) was estimated according to projected durations of remissions, assuming continued relapse rates as seen in year two of DiRECT and the consequent life expectancy, quality of life and healthcare costs.ResultsThe two-year intervention cost was EUR 1,580 per participant, with over eighty percent of the costs incurred in year one. Compared with the control group, medication savings were EUR 259 (95% confidence interval [CI]: 166–352) for anti-diabetes drugs and EUR 29 (95% CI: 12–47) for anti-hypertensive medications. The intervention was modeled with a lifetime horizon to achieve a mean 0.06 (95% CI: 0.04–0.09) gain in QALYs for the DiRECT population and a mean total lifetime cost saving per participant of EUR 1,497 (95% CI: 755–2,331), with the intervention becoming cost-saving within six years.ConclusionsThe intensive weight loss and maintenance program reduced the cost of anti-diabetes drugs through improved metabolic control, achieved diabetes remission in over one-third of participants, and reduced total healthcare contacts and costs over two years. A substantial lifetime healthcare cost saving is anticipated from periods of diabetes remission and delaying complications. Healthcare resources could be shifted cost effectively to establish diabetes remission services, using the existing DiRECT intervention, even if remissions are only maintained for limited durations. However, more research investment is needed to further improve weight-loss maintenance and extend remissions.