Impact of investigator initiated trials and industry sponsored trials on medical practice (IMPACT): rationale and study design

Background: The German Research Foundation (DFG) and the Federal Ministry of Education and Research (BMBF) initiated large research programs to foster high quality clinical research in the academic area. These investigator initiated trials (IITs) cover important areas of medical research and often go beyond the scope of industry sponsored trials (ISTs). The purpose of this project was to understand to what extent results of randomized controlled IITs and ISTs have an impact on medical practice, measured by their availability for decisions in healthcare and their implementation in clinical practice. We aimed to determine study characteristics influencing a trial's impact such as type of sponsor and place of conduct. In this article, we describe the rationale and design of this project and present the characteristics of the trials included in our study cohort. Methods: The research impact of the following sub-cohorts was compared: German IITs (funded by DFG and BMBF or by other German non-commercial organizations), international IITs (without German contribution), German ISTs, and international ISTs. Trials included were drawn from the DFG-/BMBF-Websites, the German Clinical Trials Register, and from ClinicalTrials.gov . Research impact was measured as follows: 1) proportion of published trials, 2) time to publication, 3) proportion of publications appropriately indexed in biomedical databases, 4) proportion of openly accessible publications, 5) broadness of publication's target group, 6) citation of publications by systematic reviews or meta-analyses, and 7) appearance of publications or citing systematic reviews or meta-analyses in clinical practice guidelines. We also aimed to identify study characteristics associated with the impact of trials. Results: We included 691 trials: 120 German IITs, 200 International IITs, 171 German ISTs and 200 International ISTs. The median number of participants was 150, 30% were international trials and 70% national trials, 48% drug-trials and 52% non-drug trials. Overall, 72% of the trials had one pre-defined primary endpoint, 28% two or more (max. 36). Conclusions: The results of this project deepen our understanding of the impact of biomedical research on clinical practice and healthcare policy, add important insights for the efficient allocation of scarce research resources and may facilitate providing accountability to the different stakeholders involved

Nonregistration, discontinuation, and nonpublication of randomized trials: A repeated metaresearch analysis

BACKGROUND We previously found that 25% of 1,017 randomized clinical trials (RCTs) approved between 2000 and 2003 were discontinued prematurely, and 44% remained unpublished at a median of 12 years follow-up. We aimed to assess a decade later (1) whether rates of completion and publication have increased; (2) the extent to which nonpublished RCTs can be identified in trial registries; and (3) the association between reporting quality of protocols and premature discontinuation or nonpublication of RCTs. METHODS AND FINDINGS We included 326 RCT protocols approved in 2012 by research ethics committees in Switzerland, the United Kingdom, Germany, and Canada in this metaresearch study. Pilot, feasibility, and phase 1 studies were excluded. We extracted trial characteristics from each study protocol and systematically searched for corresponding trial registration (if not reported in the protocol) and full text publications until February 2022. For trial registrations, we searched the (i) World Health Organization: International Clinical Trial Registry Platform (ICTRP); (ii) US National Library of Medicine (ClinicalTrials.gov); (iii) European Union Drug Regulating Authorities Clinical Trials Database (EUCTR); (iv) ISRCTN registry; and (v) Google. For full text publications, we searched PubMed, Google Scholar, and Scopus. We recorded whether RCTs were registered, discontinued (including reason for discontinuation), and published. The reporting quality of RCT protocols was assessed with the 33-item SPIRIT checklist. We used multivariable logistic regression to examine the association between the independent variables protocol reporting quality, planned sample size, type of control (placebo versus other), reporting of any recruitment projection, single-center versus multicenter trials, and industry versus investigator sponsoring, with the 2 dependent variables: (1) publication of RCT results; and (2) trial discontinuation due to poor recruitment. Of the 326 included trials, 19 (6%) were unregistered. Ninety-eight trials (30%) were discontinued prematurely, most often due to poor recruitment (37%; 36/98). One in 5 trials (21%; 70/326) remained unpublished at 10 years follow-up, and 21% of unpublished trials (15/70) were unregistered. Twenty-three of 147 investigator-sponsored trials (16%) reported their results in a trial registry in contrast to 150 of 179 industry-sponsored trials (84%). The median proportion of reported SPIRIT items in included RCT protocols was 69% (interquartile range 61% to 77%). We found no variables associated with trial discontinuation; however, lower reporting quality of trial protocols was associated with nonpublication (odds ratio, 0.71 for each 10% increment in the proportion of SPIRIT items met; 95% confidence interval, 0.55 to 0.92; p = 0.009). Study limitations include that the moderate sample size may have limited the ability of our regression models to identify significant associations. CONCLUSIONS We have observed that rates of premature trial discontinuation have not changed in the past decade. Nonpublication of RCTs has declined but remains common; 21% of unpublished trials could not be identified in registries. Only 16% of investigator-sponsored trials reported results in a trial registry. Higher reporting quality of RCT protocols was associated with publication of results. Further efforts from all stakeholders are needed to improve efficiency and transparency of clinical research

Sowing Seeds for Healthier Diets: Children’s Perspectives on School Gardening

School gardening programmes are among the most promising interventions to improve children’s vegetable intake. Yet, low vegetable intake among children remains a persistent public health challenge. This study aimed to explore children’s perspectives, experiences, and motivations concerning school gardening in order to better understand and increase its potential for health promotion. Using participant observation and semi-structured interviews, we provided 45 primary schoolchildren (9–10 years) from Amsterdam, who participated in a comprehensive year-round school gardening programme, the opportunity to share their experiences and ideas on school gardening. Children particularly expressed enjoyment of the outdoor gardening portion of the programme as it enabled them to be physically active and independently nurture their gardens. Harvesting was the children’s favourite activity, followed by planting and sowing. In contrast, insufficient gardening time and long explanations or instructions were especially disliked. Experiencing fun and enjoyment appeared to play a vital role in children’s motivation to actively participate. Children’s suggestions for programme improvements included more autonomy and opportunities for experimentation, and competition elements to increase fun and variety. Our results indicate that gaining insight into children’s perspectives allows matching school gardening programmes more to children’s wishes and expectations, thereby potentially enhancing their intrinsic motivation for gardening and vegetable consumption

‘I Eat the Vegetables because I Have Grown them with My Own Hands’: Children's Perspectives on School Gardening and Vegetable Consumption

Inadequate vegetable consumption is a global public health concern related to numerous health risks. A promising intervention to increase children's vegetable consumption is school gardening, although earlier studies have shown mixed results. This study explores how gardening might contribute to changed attitudes towards eating vegetables from a child's perspective. Findings are based on qualitative research with children in Amsterdam, the Netherlands. We reflect on how children enact agency regarding their vegetables. Results show that children report that changes occur in their attitudes towards vegetables as they not only eat more vegetables but also advocate the consumption of vegetables at home

Sowing Seeds for Healthier Diets: Children's Perspectives on School Gardening

School gardening programmes are among the most promising interventions to improve children's vegetable intake. Yet, low vegetable intake among children remains a persistent public health challenge. This study aimed to explore children's perspectives, experiences, and motivations concerning school gardening in order to better understand and increase its potential for health promotion. Using participant observation and semi-structured interviews, we provided 45 primary schoolchildren (9-10 years) from Amsterdam, who participated in a comprehensive year-round school gardening programme, the opportunity to share their experiences and ideas on school gardening. Children particularly expressed enjoyment of the outdoor gardening portion of the programme as it enabled them to be physically active and independently nurture their gardens. Harvesting was the children's favourite activity, followed by planting and sowing. In contrast, insufficient gardening time and long explanations or instructions were especially disliked. Experiencing fun and enjoyment appeared to play a vital role in children's motivation to actively participate. Children's suggestions for programme improvements included more autonomy and opportunities for experimentation, and competition elements to increase fun and variety. Our results indicate that gaining insight into children's perspectives allows matching school gardening programmes more to children's wishes and expectations, thereby potentially enhancing their intrinsic motivation for gardening and vegetable consumption

Investigator initiated trials versus industry sponsored trials - translation of randomized controlled trials into clinical practice (IMPACT)

Background!#!Healthcare decisions are ideally based on clinical trial results, published in study registries, as journal articles or summarized in secondary research articles. In this research project, we investigated the impact of academically and commercially sponsored clinical trials on medical practice by measuring the proportion of trials published and cited by systematic reviews and clinical guidelines.!##!Methods!#!We examined 691 multicenter, randomized controlled trials that started in 2005 or later and were completed by the end of 2016. To determine whether sponsorship/funding and place of conduct influence a trial's impact, we created four sub-cohorts of investigator initiated trials (IITs) and industry sponsored trials (ISTs): 120 IITs and 171 ISTs with German contribution compared to 200 IITs and 200 ISTs without German contribution. We balanced the groups for study phase and place of conduct. German IITs were funded by the German Research Foundation (DFG), the Federal Ministry of Education and Research (BMBF), or by another non-commercial research organization. All other trials were drawn from the German Clinical Trials Register or ClinicalTrials.gov. We investigated, to what extent study characteristics were associated with publication and impact using multivariable logistic regressions.!##!Results!#!For 80% of the 691 trials, results were published as result articles in a medical journal and/or study registry, 52% were cited by a systematic review, and 26% reached impact in a clinical guideline. Drug trials and larger trials were associated with a higher probability to be published and to have an impact than non-drug trials and smaller trials. Results of IITs were more often published as a journal article while results of ISTs were more often published in study registries. International ISTs less often gained impact by inclusion in systematic reviews or guidelines than IITs.!##!Conclusion!#!An encouraging high proportion of the clinical trials were published, and a considerable proportion gained impact on clinical practice. However, there is still room for improvement. For publishing study results, study registries have become an alternative or complement to journal articles, especially for ISTs. IITs funded by governmental bodies in Germany reached an impact that is comparable to international IITs and ISTs

Effects of nutrition intervention strategies in the primary prevention of overweight and obesity in school settings: a protocol for a systematic review and network meta-analysis

Background!#!Overweight and obesity in children and adolescents are major public health challenges affecting quality of life and representing important risk factors in the development of non-communicable diseases. School environments provide great possibilities for the primary prevention of overweight and obesity and different school-based nutrition interventions are available. However, existing research on school-based nutrition interventions has important limitations and no network meta-analysis (NMA) has been performed yet to compare all available interventions. Therefore, the present research project aims to investigate the impact of different nutrition interventions in the school setting by comparing and ranking them using NMA methodology.!##!Methods/design!#!A systematic literature search will be performed in 11 electronic databases (PubMed, the Cochrane Library, Web of Science, ERIC, PsycINFO, CAB Abstracts, Campbell Library, BiblioMap EPPI, Australian Education Index, Joanna Briggs Institute Evidence-Based Practice Database and Practice-based Evidence in Nutrition Database). Parallel or cluster randomized controlled trials (RCTs) meeting the following criteria will be included: (1) generally healthy school students aged 4-18 years, (2) school-based intervention with ≥ 1 nutrition component, and (3) assessed anthropometric (overweight/obesity risk, body weight change, weight Z-score, [standardized] body mass index, body fat, waist circumference) and/or diet-quality measures (daily intake of fruits and vegetables, fat, and sugar-sweetened beverages). Random effects pairwise and NMA will be performed for these outcomes and surface under the cumulative ranking curve (SUCRA) estimated (P-score). Where possible, component NMA (CNMA) will be used additionally. Subgroup analyses are carried out for intervention duration, gender, age of school students, socioeconomic status, and geographical location, and sensitivity analyses by excluding high risk of bias RCTs.!##!Discussion!#!This systematic review and NMA will be the first to both directly and indirectly compare and rank different school-based nutrition interventions for the primary prevention of overweight and obesity in childhood and adolescence. Our analyses will provide important insights about the effects of the different interventions and show which are the most promising. The results of our study can help inform the design of new studies and will be of value to anyone interested in developing successful, evidence-based nutrition interventions in school settings.!##!Systematic review registration!#!PROSPERO: CRD42020220451

Experiencing the risk of overutilizing opioids among patients with chronic noncancer pain in ambulatory care (ERONA): an exploratory, randomized controlled trial

Introduction. The US opioid crisis and increasing prescription rates in Europe suggest inappropriate risk perceptions and behaviors of people who prescribe, take, or advise on opioids: physicians, patients, and pharmacists. Findings from cognitive and decision science in areas other than drug safety suggest that people’s risk perception and behavior can differ depending on whether they learned about a risk through personal experience or description. ERONA is the first-ever conducted trial that aims at investigating the effects of these two modes of learning on individuals’ risk perception and behavior in the long-term administration of WHO-III opioids in chronic noncancer pain. Methods and analysis. ERONA—an exploratory, randomized controlled online survey intervention trial with two parallel arms—will examine the opioid-associated risk perception and behavior of four groups involved in the long-term administration of WHO-III opioids: (1) family physicians, (2) physicians specialized in pain therapy, (3) patients with chronic (≥3 months) noncancer pain, and (4) pharmacists who regularly dispense narcotic substances. Participants will be randomly assigned to one of two online risk education interventions, description-based or experience-based. Both interventions will present the best medical evidence available. Participants will be queried at baseline and after intervention on their risk perception of opioids’ benefit–harm ratio, their medical risk literacy, and their current/intended risk behavior (in terms of prescribing, taking, or counselling, depending on study group). A follow-up will occur after 9 months, when participants will be queried on their actual risk behavior. The study was developed by the authors and will be conducted by the market research institution IPSOS Health. Ethics and dissemination. The study was approved by the Institutional Review Board of the Max Planck Institute for Human Development. Results will be disseminated through peer-reviewed journals, conference presentations, and social media

Everyday Lives of Middle-Aged Persons with Multimorbidity:A Mixed Methods Systematic Review

The healthcare burden of patients with multimorbidity may negatively affect their family lives, leisure time and professional activities. This mixed methods systematic review synthesizes studies to assess how multimorbidity affects the everyday lives of middle-aged persons, and identifies skills and resources that may help them overcome that burden. Two independent reviewers screened title/abstracts/full texts in seven databases, extracted data and used the Mixed Methods Appraisal Tool (MMAT) to assess risk of bias (RoB). We synthesized findings from 44 studies (49,519 patients) narratively and, where possible, quantitatively. Over half the studies provided insufficient information to assess representativeness or response bias. Two studies assessed global functioning, 15 examined physical functioning, 18 psychosocial functioning and 28 work functioning. Nineteen studies explored skills and resources that help people cope with multimorbidity. Middle-aged persons with multimorbidity have greater impairment in global, physical and psychosocial functioning, as well as lower employment rates and work productivity, than those without. Certain skills and resources help them cope with their everyday lives. To provide holistic and dynamic health care plans that meet the needs of middle-aged persons, health professionals need greater understanding of the experience of coping with multimorbidity and the associated healthcare burden

Everyday lives of middle-aged persons living with multimorbidity: protocol of a mixed-methods systematic review.

INTRODUCTION: Multimorbidity is the simultaneous occurrence of several (chronic) diseases. Persons living with multimorbidity not only have complex care needs, but the burden of care often has a negative impact on their family lives, leisure time and professional activities. The aim of this project is to systematically review the literature to assess how multimorbidity affects the everyday lives of middle-aged persons, and to find out what abilities and resources help in the development of coping strategies to overcome the challenges of living with it. METHODS AND ANALYSIS: We will systematically search for studies reporting on the everyday life experiences of middle-aged persons (30–60 years) with multimorbidity (≥2 chronic conditions) in MEDLINE, CINAHL, PsycINFO, Social Sciences Citation Index, Social Sciences Citation Index Expanded, PSYNDEX and The Cochrane Library from inception. We will include all primary studies that use quantitative, qualitative and mixed methodologies, irrespective of publication date/study setting. Two independent reviewers will screen titles/abstracts/full texts, extract data from the selected studies and present evidence in terms of study/population characteristics, data collection method and the phenomenon of interest, that is, everyday life experiences of middle-aged persons with multimorbidity. Risk of bias will be independently assessed by two reviewers using the Mixed Methods Appraisal Tool. We will use a convergent integrated approach on qualitative/quantitative studies, whereby information will be synthesised narratively and, if possible, quantitatively. ETHICS AND DISSEMINATION: Ethical approval is not required due to the nature of the proposed systematic review. Results from this research will be disseminated at relevant (inter)national conferences and via publication in peer-reviewed journals. PROSPERO REGISTRATION NUMBER: CRD42021226699