Analysis of the first 2645 registrations at the research registry®: A global repository for all study types involving human participants.

BACKGROUND: The Declaration of Helsinki has called for the registration of all research studies involving human participants. Despite this, prior registries did not allow registration certain study types, or retrospective registration. The Research Registry® (www.researchregistry.com) was established in 2015 to provide a venue of registration for any study involving human participants. METHODS: and analysis: This retrospective database analysis describes the first 3000 registrations received by the Research Registry®. Since the launch of the Registry in 2015, we have collected data on each registration and excluded inappropriate registrations through a weekly curation process. The characteristics of all studies registered is presented. Each registration was marked against a quality score by two researchers acting independently, and we describe how this has changed over time. No ethical approval was required for this data only study including no human participants. RESULTS: Of 3000 registrations, we included 2645 that were submitted to the registry between February 2015 and October 2017. The number of registrations increased year on year, and we now receive between 60 and 80 registrations per month. One fifth of registrations were from China (537 [20.3%]). Retrospective observational studies were most commonly registered (1125 [42.5%]), and studies included in excess of 20 million patients (median 80 [IQR:25-200]). The quality score of registrations improved over the time (Kruskal-Wallis p < 0.05), and the 'control/comparator' component of the quality score was most poorly completed (completed by 1199 [54%]). CONCLUSION: The Research Registry® has received registrations on over 2500 registrations, including in excess of 20 million patients, with the quality of registrations improving over time. Retrospective observational studies and case series are the most commonly registered.

Past and future trends in cancer and biomedical research: a comparison between Egypt and the world using PubMed-indexed publications.

BACKGROUND: PubMed is a free web literature search service that contains almost 21 millions of abstracts and publications with almost 5 million user queries daily. The purposes of the study were to compare trends in PubMed-indexed cancer and biomedical publications from Egypt to that of the world and to predict future publication volumes. METHODS: The PubMed was searched for the biomedical publications between 1991 and 2010 (publications dates). Affiliation was then limited to Egypt. Further limitation was applied to cancer, human and animal publications. Poisson regression model was used for prediction of future number of publications between 2011 and 2020. RESULTS: Cancer publications contributed 23% to biomedical publications both for Egypt and the world. Egyptian biomedical and cancer publications contributed about 0.13% to their world counterparts. This contribution was more than doubled over the study period. Egyptian and world's publications increased from year to year with rapid rise starting the year 2003. Egyptian as well as world's human cancer publications showed the highest increases. Egyptian publications had some peculiarities; they showed some drop at the years 1994 and 2002 and apart from the decline in the animal: human ratio with time, all Egyptian publications in the period 1991-2000 were significantly more than those in 2001-2010 (P < 0.05 for all). By 2020, Egyptian biomedical and cancer publications will increase by 158.7% and 280% relative to 2010 to constitute 0.34% and 0.17% of total PubMed publications, respectively. CONCLUSIONS: The Egyptian contribution to world's biomedical and cancer publications needs significant improvements through research strategic planning, setting national research priorities, adequate funding and researchers' training.

Assessment of donor fear enhances prediction of presyncopal symptoms among volunteer blood donors.

BACKGROUND: Fear is an important contributor to the risk of presyncopal reactions to blood donation. However, concern that asking donors about their fears may increase the risk of reactions is a potential impediment to incorporating fear assessment into donor screening. STUDY DESIGN AND METHODS: Before donation, participants responded to a series of questions that either did (n = 488) or did not (n = 494) include questions related to fear of seeing blood drawn. Immediately after donation all participants provided ratings of presyncopal reactions. RESULTS: Among those asked predonation fear questions, fear was most strongly related to presyncopal symptoms when compared against other donor characteristics (e.g., age, number of prior donations, body mass index, estimated blood volume, blood pressure, and pulse). However, Mann-Whitney U tests revealed that being asked about fear before donation was not associated with higher reports of presyncopal reactions for the sample as a whole, nor among novice donors. Further, regression analyses indicated that fear remained a significant predictor of presyncopal reactions in final models that included age and number of prior donations as significant predictors. CONCLUSION: Predonation assessment of fear of blood draws may help to identify donors who are most likely to benefit from brief interventions designed to enhance donor coping, reduce risk of presyncopal reactions, and increase donor retention.

Association of trial registration with the results and conclusions of published trials of new oncology drugs.

BACKGROUND: Registration of clinical trials has been introduced largely to reduce bias toward statistically significant results in the trial literature. Doubts remain about whether advance registration alone is an adequate measure to reduce selective publication, selective outcome reporting, and biased design. One of the first areas of medicine in which registration was widely adopted was oncology, although the bulk of registered oncology trials remain unpublished. The net influence of registration on the literature remains untested. This study compares the prevalence of favorable results and conclusions among published reports of registered and unregistered randomized controlled trials of new oncology drugs. METHODS: We conducted a cross-sectional study of published original research articles reporting clinical trials evaluating the efficacy of drugs newly approved for antimalignancy indications by the United States Food and Drug Administration (FDA) from 2000 through 2005. Drugs receiving first-time approval for indications in oncology were identified using the FDA web site and Thomson Centerwatch. Relevant trial reports were identified using PubMed and the Cochrane Library. Evidence of advance trial registration was obtained by a search of clinicaltrials.gov, WHO, ISRCTN, NCI-PDQ trial databases and corporate trial registries, as well as articles themselves. Data on blinding, results for primary outcomes, and author conclusions were extracted independently by two coders. Univariate and multivariate logistic regression identified associations between favorable results and conclusions and independent variables including advance registration, study design characteristics, and industry sponsorship. RESULTS: Of 137 original research reports from 115 distinct randomized trials assessing 25 newly approved drugs for treating cancer, the 54 publications describing data from trials registered prior to publication were as likely to report statistically significant efficacy results and reach conclusions favoring the test drug (for results, OR = 1.77; 95% CI = 0.87 to 3.61) as reports of trials not registered in advance. In multivariate analysis, reports of prior registered trials were again as likely to favor the test drug (OR = 1.29; 95% CI = 0.54 to 3.08); large sample sizes and surrogate outcome measures were statistically significant predictors of favorable efficacy results at p < 0.05. Subgroup analysis of the main reports from each trial (n = 115) similarly indicated that registered trials were as likely to report results favoring the test drug as trials not registered in advance (OR = 1.11; 95% CI = 0.44 to 2.80), and also that large trials and trials with nonstringent blinding were significantly more likely to report results favoring the test drug. CONCLUSIONS: Trial registration alone, without a requirement for full reporting of research results, does not appear to reduce a bias toward results and conclusions favoring new drugs in the clinical trials literature. Our findings support the inclusion of full results reporting in trial registers, as well as protocols to allow assessment of whether results have been completely reported.

Mortality in British military participants in human experimental research into chemical warfare agents at Porton Down: cohort study.

OBJECTIVE: To investigate any long term effects on mortality in participants in experimental research related to chemical warfare agents from 1941 to 1989. DESIGN: Historical cohort study. Data sources Archive of UK government research facility at Porton Down, UK military personnel records, and national death and cancer records. Participants 18,276 male members of the UK armed forces who had spent one or more short periods (median 4 days between first and last test) at Porton Down and a comparison group of 17,600 non-Porton Down veterans followed to 31 December 2004. MAIN OUTCOME MEASURES: Mortality rate ratio of Porton Down compared with non-Porton Down veterans and standardised mortality ratio of each veteran group compared with the general population. Both ratios adjusted for age group and calendar period. RESULTS: Porton Down veterans were similar to non-Porton Down veterans in year of enlistment (median 1951) but had longer military service (median 6.2 v 5.0 years). After a median follow-up of 43 years, 40% (7306) of Porton Down and 39% (6900) of non-Porton Down veterans had died. All cause mortality was slightly greater in Porton Down veterans (rate ratio 1.06, 95% confidence interval 1.03 to 1.10, P<0.001), more so for deaths outside the UK (1.26, 1.09 to 1.46). Of 12 cause specific groups examined, rate ratios in Porton Down veterans were increased for deaths attributed to infectious and parasitic (1.57, 1.07 to 2.29), genitourinary (1.46, 1.04 to 2.04), circulatory (1.07, 1.01 to 1.12), and external (non-medical) (1.17, 1.00 to 1.37) causes and decreased for deaths attributed to in situ, benign, and unspecified neoplasms (0.60, 0.37 to 0.99). There was no clear relation between type of chemical exposure and cause specific mortality. The mortality in both groups of veterans was lower than that in the general population (standardised mortality ratio 0.88, 0.85 to 0.90; 0.82, 0.80 to 0.84). CONCLUSIONS: Mortality was slightly higher in Porton Down than non-Porton Down veterans. With lack of information on other important factors, such as smoking or service overseas, it is not possible to attribute the small excess mortality to chemical exposures at Porton Down.

Cancer morbidity in British military veterans included in chemical warfare agent experiments at Porton Down: cohort study.

OBJECTIVE: To determine cancer morbidity in members of the armed forces who took part in tests of chemical warfare agents from 1941 to 1989. DESIGN: Historical cohort study, with cohort members followed up to December 2004. DATA SOURCE: Archive of UK government research facility at Porton Down, UK military personnel records, and national death and cancer records. PARTICIPANTS: All veterans included in the cohort study of mortality, excluding those known to have died or been lost to follow-up before 1 January 1971 when the UK cancer registration system commenced: 17,013 male members of the UK armed forces who took part in tests (Porton Down veterans) and a similar group of 16,520 men who did not (non-Porton Down veterans). MAIN OUTCOME MEASURES: Cancer morbidity in each group of veterans; rate ratios, with 95% confidence intervals, adjusted for age group and calendar period. RESULTS: 3457 cancers were reported in the Porton Down veterans compared with 3380 cancers in the non-Porton Down veterans. While overall cancer morbidity was the same in both groups (rate ratio 1.00, 95% confidence interval 0.95 to 1.05), Porton Down veterans had higher rates of ill defined malignant neoplasms (1.12, 1.02 to 1.22), in situ neoplasms (1.45, 1.06 to 2.00), and those of uncertain or unknown behaviour (1.32, 1.01 to 1.73). CONCLUSION: Overall cancer morbidity in Porton Down veterans was no different from that in non-Porton Down veterans.

Revisão ética e termo de consentimento livre e esclarecido nas publicações de pesquisas cardiovasculares na Argentina / Ethical review and informed consent in cardiovascular research reports in Argentina

FUNDAMENTO: Existem evidências de que algumas vezes os requisitos de aprovação do Conselho de Revisão Institucional (IRB) e obtenção de termo de consentimento livre e esclarecido (TCLE) para a realização de pesquisas com seres humanos não são cumpridos nas publicações argentinas de pesquisas cardiovasculares. OBJETIVO: Analisar a freqüência com que a aprovação do IRB e o TCLE são obtidos na Argentina. MÉTODOS: Pedimos que cem autores de artigos apresentados no nosso encontro científico de 2006 respondessem a um questionário. RESULTADOS: Trinta e seis por cento dos questionários foram devolvidos com confirmação de revisão ética, 34 por cento responderam que não havia sido feita, 23 por cento disseram que tinham sido isentados da revisão e 7 por cento não foram devolvidos. A maioria dos artigos submetidos à revisão era de estudos farmacológicos ou pesquisas sobre avaliação de novos dispositivos. A maioria dos artigos que não passaram por revisão ética era referente a pesquisas epidemiológicas ou estudos para avaliação de métodos não-invasivos; 60 por cento dos estudos farmacológicos, implante celular ou avaliação de novos dispositivos atendiam às exigências das normas federais. CONCLUSÃO: A taxa de revisão ética e a obtenção do TCLE nas publicações argentinas de pesquisas cardiovasculares varia entre os artigos. A maior parte das pesquisas referentes a estudos observacionais prospectivos e cerca de 50 por cento dos protocolos de intervenções ou procedimentos invasivos não relatam a realização de revisão ética. Essa porcentagem elevada de artigos que não são submetidos à revisão ética indica a existência de falhas legais e éticas que devem ser discutidas e corrigidas.

BACKGROUND: Requirements for Institutional Review Board approval and informed consent for research involving human subjects have existed for more than 2 decades. However, evidence of fulfillment of these requirements is sometimes lacking in cardiovascular research reports in Argentina. Since ethical standards vary between committees, there may be some confusion among researchers regarding the need for an ethical review when conducting low risk research. OBJECTIVE: To examine the frequency of obtaining an ethical review and informed consent in cardiovascular research in Argentina. METHODS: Through a questionnaire, we contacted authors of 100 reports submitted to our annual scientific meeting during 2006. RESULTS: Thirty six per cent of questionnaires were resubmitted with confirmation of ethical review, 34 percent responded that ethical review was not obtained, 23 percent reported as being exempt and 7 percent were never resubmitted. Most articles obtaining ethical review were pharmacological trials or research involving assessment of new devices. On the other hand, most articles reporting lack of or exemption from ethical review come from epidemiological research or studies evaluating non-invasive methods. Sixty percent of phase IV pharmacological trials, research on cellular implantation or assessment of new devices met federal regulations requirements. CONCLUSION: The rate of ethical review and use of informed consent in cardiovascular reports in Argentina vary among articles. Most research involving prospective observational studies and nearly 50 percent of protocols including intervention or invasive procedures do not report ethical review. This high proportion of articles lacking ethical review suggests the presence of legal and ethical flaws which should be discussed and overcome.

Ethical process in human research published in thoracic surgery journals.

BACKGROUND: Media reports of ethical transgressions in research with human subjects have increasingly focused attention on clinical investigators and have served to undermine public confidence in medical research. A series of editorials in The Annals of Thoracic Surgery and The Journal of Thoracic and Cardiovascular Surgery in 2002 and 2003 emphasized integrity in research publication. We investigated the extent to which the ethical process was mentioned in reports of thoracic surgical research with human subjects since 2002. METHODS: We reviewed all reports of research involving human subjects published in these journals during the first 6 months of 2002, the first 6 months of 2003, and the last 6 months of 2004 (n = 273, 291 and 288 for each time period, respectively with a total of 852). RESULTS: Ethical process was mentioned in 346 of 852 (41%) investigations. Comparing US and non-US studies, the rates of mentioning ethical process for prospective studies were 76 of 83 (92%) and 178 of 216 (82%), respectively, and for retrospective studies were 75 of 220 (34%) and 18 of 334 (5%), respectively. Between 2002 and 2004, the rates of mentioning ethical process for prospective studies increased from 79 of 101 (78%) to 80 of 89 (90%), and for retrospective studies it increased from 17 of 172 (10%) to 59 of 199 (30%). CONCLUSIONS: There was a significant increase in mention of ethical process from early 2002 to late 2004; however, documentation of appropriate ethical process in human research published in cardiothoracic journals remains less than ideal. The main burden of ensuring ethical process in human investigations rests with researchers, their institutions, and institutional review boards; however, editors can help rectify this problem by requiring adherence to national and international standards in the human subjects' research studies they publish. In adhering to ethical standards, investigators respect the research subjects' right of self-determination and foster public confidence in human research.

An overview of adverse events reported by participants in CDC's anthrax vaccine and antimicrobial availability program.

PURPOSE: The CDC's Anthrax Vaccine and Antibiotic Availability Program was implemented under an Investigational New Drug (IND) application to provide additional post-exposure prophylaxis for individuals potentially exposed to Bacillus anthracis in the fall of 2001. Participants were provided with two options: (1) 40 additional days of antimicrobial prophylaxis (i.e., ciprofloxacin, doxycycline, or amoxicillin); or (2) 40 additional days of antimicrobial prophylaxis plus three doses of anthrax vaccine adsorbed (AVA). METHODS: Participants were monitored for adverse events (AEs). Participants were asked to complete 2-week AE diaries for 6 weeks post-enrollment, and approximately 2 months after enrollment, active surveillance was conducted through telephone interviews with 1113 (64%) participants. RESULTS: A total of 1727 of approximately 10 000 previously prophylaxed persons enrolled to receive 40 additional days of antibiotics. Of these, 199 opted at enrollment to receive three doses of AVA in addition to the additional 40 days of antibiotic. Overall, 28% of participants reported at least one AE on their diaries. Results varied by surveillance mechanism, the diary data indicated differences in the proportion reporting AEs between participants receiving antibiotic only and participants receiving antibiotic and AVA. However, during the active 2-month telephone follow-up, the rates of AEs reported for both the antibiotic only and antibiotic plus AVA treatment regimens were similar. Additionally, ciprofloxacin and doxycycline had similar AE profiles, with only rigors reported significantly more often among ciprofloxacin recipients. CONCLUSIONS: Overall, the rates of AEs experienced by all participants were acceptable given the seriousness of potential B. anthracis exposure.

Almost 50,000 volunteers participate at Redome, the Brazilian Bone Marrow Donor Registry.

Striking progress has been observed in the number of volunteer donors for hematopoietic stem cell transplantation in the last years in Brazil. By the end of 1998, the number of donors barely reached 4200 but it has grown progressively. It was close to 48,000 by the end of May 1993. It is possible to notice a steady increase from the first (1993 to 2000) to the last years (2001 to 2003). The regulation of each procedure by the Brazilian Health System, with the collaboration of the Hematology Societies, was essential for the success of Redome and for the stem cell transplantation program in Brazil. However, when analyzing these results some problems were detected: 95% of Redome donors come from the south and southeastern regions of the country, while few donors are from the north, northeast, and central parts of Brazil. The different miscegenation of races in different regions and states of Brazil makes this an important issue: to represent the whole Brazilian population, Redome must improve the donor search in such places. It also became clear that several other centers involved in unrelated hematopoietic transplantation must be accredited to avoid a long line of patients with compatible donors a waiting transplantation.

Voluntary donors-need for a second look.

Voluntary non-remunerated blood donation is the source of the safest blood supply to the transfusion service. In the Indian set up where voluntary donations are fewer and poorly structured, safety of blood could still be compromised. This study was carried out to find out the seroprevalence of transfusion transmitted diseases among replacement and voluntary donors. A retrospective study of replacement and voluntary donors over a three and a half year period was carried out and the seroprevalence for human immunodeficiency virus (HIV), hepatitis B, hepatitis C, syphilis and malaria was noted. A total of 41122 donors were studied comprising of 94.7% replacement and 5.3% voluntary donors. The prevalence of transfusion transmitted diseases was marginally higher among voluntary donors (3.3%) as compared to replacement donors (2.9%). All cases of HIV were seen in the replacement donors while the figures for hepatitis B and C were marginally higher in the voluntary donors (p>0.05). Voluntary donations in our study were not voluntary in the real sense. There is a need to work on building a stronger voluntary donor base and to create awareness among the populace in order to gradually abolish the replacement donations; thereby ensuring the safety of blood and its products.

Review of procedures for protecting human subjects in recent clinical studies of pesticides.

Arguments have been made for and against the regulatory use of data from human subjects on both scientific and ethical grounds. One argument against the use of data from human clinical studies involving pesticides asserts that such data are obtained from studies that do not follow the Common Rule (40 CFR 26), which provides procedures for protecting human subjects in studies funded by federal agencies, including the U.S. Environmental Protection Agency (U.S. EPA). Although privately conducted studies using human subjects are not legally subject to or required to comply with the Common Rule, the protections of the Declaration of Helsinki and the International Conference on Harmonisation (ICH) Good Clinical Practice are commonly followed. We sought to answer the question of whether recent human clinical studies with insecticides performed according to Good Clinical Practice provided volunteers with the same protections as the Common Rule. All three sets of guidance have in common the intent to protect volunteer human subjects by providing standards for the conduct of studies in which they participate. This analysis compares the elements of the Common Rule with comparable elements from the Declaration of Helsinki and Good Clinical Practice to evaluate similarities and differences in procedural requirements. It then evaluates the documentation from 15 recent human studies of twelve insecticides conducted at four clinical laboratories in order to determine whether the conduct of those studies is consistent with the protections of the Common Rule. There were some cases for which we could not verify compliance with certain Common Rule elements; however, based on our evaluation it is apparent that the studies we reviewed were conducted in a manner substantially consistent with the fundamental protections of the Common Rule-voluntary participation, informed consent, and review by an ethical committee or institutional review board.

Participation of children in clinical research: factors that influence a parent's decision to consent.

BACKGROUND: Given the initiatives of the National Institutes of Health and other agencies to include children in research, it is important to understand the factors that influence their participation. This study was designed to identify factors that influence parents' decisions to consent to their child's participation in clinical research. METHODS: This survey study consisted of 505 parents who had been approached for permission to allow their child to participate in a clinical anesthesia or surgery study at a large tertiary care children's hospital. Regardless of whether the parents consented to (consenters, n = 411), or declined (nonconsenters, n = 94) their child's participation in a study, they were offered the opportunity to complete a questionnaire eliciting information regarding factors that had influenced their decision. RESULTS: Consenters exhibited less uncertainty in their decision making, were more trusting of the medical system, had greater understanding of the research, and believed that the environment in which consent was sought was less pressured than nonconsenters. Predictors of consent included low perceived risk, degree to which the parent read the consent document, characteristics of the consent document, parental understanding, perceived importance of the study, and perceived benefits. CONCLUSIONS: Identification of factors that influence parents' decisions to allow their child to participate in a clinical research study will be important by way of developing strategies to improve the manner in which study information is disclosed and to ensure that parents are truly informed.

Older adolescents with cancer in North America deficits in outcome and research.

In the two decades from the mid 1970s to the mid 1990s, the proportion of 5-year survivors among children in North America with cancer has increased nearly 40%. Advances in otherwise fatal leukemias, lymphomas, sarcomas, brain tumors, germ cell neoplasms and cancer of the kidney account for much of the improvement. Unfortunately, older adolescents have not fared as well. Their epidemiological, medical, physical, psychological and social needs remain largely unmet despite their age juxtaposition with younger patients whose outcomes have so much improved. In the United States and Canada, cancer in adolescents 15 to 19 years of age occurs at nearly twice the rate observed in 5 to 14 year-olds. Many of the types of cancer that occur in older adolescents are unique to this age group, and the pattern of distribution occurs at no other age interval. Overall, the cancers in older adolescents are more similar to the spectrum of cancer in children than to the common types of cancer in adults, but they are also distinctly different and require an age-specific approach. There is evidence of a lower degree in reduction in cancer mortality in the United States and Canada in this age range than in younger or older persons. Moreover, the disparity appears to be increasing. The improvement in 5-year survival from diagnosis of cancer from the mid 1970s to the early 1990s was lower than the rate of improvement in the younger age groups. Survival rates of older adolescents with cancer in the general population have not improved as much, especially in comparison with results of the national pediatric cooperative cancer groups. In the United States and Canada, only about 5% of 15 to 25 year-olds with cancer are entered onto clinical trials, in contrast to 60% to 65% of younger patients. Thus, cancer during adolescence and early adulthood has been relatively neglected and merits enhanced national research programs and resources.

Ethical regulations for innovative surgery: the last frontier?

BACKGROUND: There are no clear federal regulations governing innovative surgery, even though general guidelines regulating research with human subjects do exist. We hypothesized that US surgeons are unaware of Department of Health and Human Services regulations, rarely seek IRB review, generally oppose outside regulation of innovative surgery, and are uncertain what constitutes innovation and research. These circumstances, if true, would pose a significant ethical problem and present potential harm to patients as unwitting subjects of research. STUDY DESIGN: In a pilot study we reviewed 527 issues of US surgical and medical journals, selecting 59 articles published between 1992 and 2000, that described innovative surgery. Corresponding authors from university hospitals (71%) and other facilities (29%) were sent an anonymous questionnaire. RESULTS: The survey was conducted between November 2000 and May 2001. Twenty-one questionnaires were returned, completed with responses, constituting a 35% overall response rate. Fourteen authors confirmed their work was research, yet only six had sought prior IRB review. The majority of authors (15 of 21) did not submit their protocol to IRB. Only seven authors had mentioned the innovative nature of the procedure in the informed consent form. Seven authors claimed familiarity with Office for Human Research Protections definitions of research and human subject. Two-thirds of the respondents stated that government regulations for the protection of human subjects of innovative surgery would not be appropriate. CONCLUSIONS: The current system of definitions, ethical theories, and voluntary professional guidelines may be inadequate to meet the challenge of surgical innovation. Further research is proposed to examine the adequacy of the existing guidelines.