It's plain and simple: transparency is good for science and in the public interest.

In the past couple of years, there has been a growing focus on the need to make scientific output accessible to a greater number of people, especially in the field of clinical research. The public are being urged to become more well-informed and to ask their doctors about taking part in clinical trials. A key finding of a report from the Association of Medical Research Charities was that all published scientific papers would benefit from having a section in plain English. Researchers running a clinical trial are expected to provide a summary of their intended research at various stages of the research process. However, there is evidence that existing summaries are of variable length and quality and not always in plain English. As a result, the National Institute for Health Research (NIHR) commissioned a review of the guidance that is available to researchers. However, recent initiatives demonstrate that there are still a number of challenges in making current research both accessible and understandable by prospective participants. BioMed Central also has a number of ongoing initiatives involving trial registration services and journals.

The bottleneck effect in lung cancer clinical trials.

Clinical trials provide the most promising way to improve treatment outcomes in cancer. This study examined the rate at which eligible patients with lung cancer, at a National Cancer Institute-designated cancer center in the South, were offered a clinical trial and explored for reasons for ineligibility. We retrospectively reviewed 300 randomly selected lung cancer patients' medical records seen in 2010, to assess clinical trial offers to eligible patients, reasons for not offering an eligible patient a trial, demographic factors associated with eligibility, and reasons for refusal among those offered a trial. Of the 300 patient charts, seven were excluded for lack of confirmed lung cancer diagnosis. Forty-six of the remaining 293 (15.7%) patients were eligible for a clinical trial. Forty-five of the 46 (97.8%) were considered for a trial by their oncologist. Thirty-five of the 45 (77.8%) were offered a trial: 15 agreed (42.9% of those offered, 5.1% of patients reviewed), 11 declined, and 9 were undecided at the end of the review window. Patients with poor Eastern Cooperative Oncology Group (ECOG) performance status levels and small cell (SC) diagnoses were significantly less likely to be eligible for a trial. Results suggest that oncologists at the cancer center are effectively presenting all eligible patients with the option of a clinical trial; however, there is a need to increase the number of approved clinical trials for patients with SC or ECOG score greater than 2.

Unequal burden of disease, unequal participation in clinical trials: solutions from African American and Latino community members.

African Americans and Latinos are underrepresented in clinical trials. The purpose of this study was to elicit solutions to participation barriers from African Americans and Latinos. Fifty-seven adults (32 African Americans, 25 Latinos) ages 50 years and older participated. The Institute of Medicine's Unequal Treatment conceptual framework was used. Six racially/ ethnically homogenous focus groups were conducted at five sites in three counties. Themes within groups and cross-cutting themes were identified. The NVIVO program was used for data classification. The data were reviewed for final coding and consensus. Shared solutions included addressing costs, recruiting in community contexts, conducting community and individualized patient education, and sharing patient safety information. Participants were unanimously in favor of clinical trials navigation recruitment interventions. Solutions specific to African Americans included diversifying research teams, recognizing past research abuses, and increasing community trust. Solutions specific to Latinos included providing low-literacy materials, providing Spanish-speaking clinicians and advocates, and clarifying that immigration status would neither be documented nor prevent participation. Solutions from African Americans and Latinos reflect their cultural backgrounds and historical experiences. The results suggest the importance of developing a tailored, barriers-focused navigation intervention to improve participation among diverse racial and ethnic populations.

Payment of research participants: current practice and policies of Irish research ethics committees.

BACKGROUND: Payment of research participants helps to increase recruitment for research studies, but can pose ethical dilemmas. Research ethics committees (RECs) have a centrally important role in guiding this practice, but standardisation of the ethical approval process in Ireland is lacking. AIM: Our aim was to examine REC policies, experiences and concerns with respect to the payment of participants in research projects in Ireland. METHOD: Postal survey of all RECs in Ireland. RESULTS: Response rate was 62.5% (n=50). 80% of RECs reported not to have any established policy on the payment of research subjects while 20% had refused ethics approval to studies because the investigators proposed to pay research participants. The most commonly cited concerns were the potential for inducement and undermining of voluntary consent. CONCLUSIONS: There is considerable variability among RECs on the payment of research participants and a lack of clear consensus guidelines on the subject. The development of standardised guidelines on the payment of research subjects may enhance recruitment of research participants.

Influence of scary beliefs about the Tuskegee Syphilis Study on willingness to participate in research.

OBJECTIVES: To assess whether scary/alarming beliefs about details on the Tuskegee Syphilis Study (TSS) are associated with willingness and/or fear to participate in biomedical research. METHODS: Scary beliefs about TSS were examined for 565 Black and White adults who had heard of the TSS. Multivariate analyses by race were used to measure association. RESULTS: No association between scary beliefs and willingness or fear to participate in research was found (P > 0.05). CONCLUSIONS: These findings provide additional evidence that awareness or detailed knowledge about the TSS does not appear today to be a major factor influencing Blacks' willingness to participate in research.

Telaprevir and boceprevir in African Americans with genotype 1 chronic hepatitis C: implications for patients and providers.

Telaprevir and boceprevir have received US Food and Drug Administration approval for use as triple therapy with pegylated interferon and ribavirin in genotype 1 chronic hepatitis C virus (HCV) infection. Clinical trials of these agents included few African Americans, despite the overwhelming need for improved therapies in this racial group. Although African Americans are predicted to have improved response rates with this new treatment paradigm, clinical trials illustrate lower rates of sustained virologic response for this racial group versus whites. African Americans with genotype 1 HCV infection appear to require longer durations of therapy than do whites to achieve a sustained virologic response. Further investigation is required to adequately counsel African Americans with genotype 1 chronic HCV infection on the efficacy of telaprevir and boceprevir in their racial group. Increased participation of this racial group in HCV clinical trials is needed to improve therapies in this difficult-to-treat population.

Quantitative valuation placed by children and teenagers on participation in two hypothetical research scenarios.

For paediatric medicine to advance, research must be conducted specifically with children. Concern about poor recruitment has led to debate about payments to child research participants. Although concerns about undue influence by such 'compensation' have been expressed, it is useful to determine whether children can relate the time and inconvenience associated with participation to the value of payment offered. This study explores children's ability to determine fair remuneration for research participation, and reviews payments to children participating in research. Forty children were interviewed before outpatient visits at two London Hospitals: Great Ormond Street Children's Hospital and the Whittington Hospital District General Hospital. Children were asked to value their involvement in two hypothetical research scenarios - the first an 'additional blood sample', the second also involving daily oral oil capsules taken for a fortnight before further venesection. Background knowledge about familiarity with money, and experience with hospitalisation was assessed. The mean valuation of involvement in the second scenario (£13.18) was higher than in the first (£2.84) (p<0.001). This higher valuation persisted when children were categorised into groups 'aged 12+' and 'below 12'. Those undergoing a blood test on the day placed a higher valuation on participation in the second scenario (£10.43, £21.67, p=0.044). These children aged 8-16 demonstrated the capacity to discern a fair valuation for participation in medical research. The monetary sums are influenced by the time and inconvenience involved in the research, and by the extent of recent experience with hospital procedures. The authors review current ethical thinking regarding payments to child research participants and suggest that a fair wage model might be an ethically acceptable way to increase participation of children in research.

Ethical dilemma of mandated contraception in pharmaceutical research at catholic medical institutions.

The Catholic Church proscribes methods of birth control other than sexual abstinence. Although the U.S. Food and Drug Administration (FDA) recognizes abstinence as an acceptable method of birth control in research studies, some pharmaceutical companies mandate the use of artificial contraceptive techniques to avoid pregnancy as a condition for participation in their studies. These requirements are unacceptable at Catholic health care institutions, leading to conflicts among institutional review boards, clinical investigators, and sponsors. Subjects may feel coerced by such mandates to adopt contraceptive techniques inconsistent with their personal situation and beliefs; women committed to celibacy or who engage exclusively in non-heterosexual activities are negatively impacted. We propose principles to insure informed consent to safeguard the rights of research subjects at Catholic institutions while mitigating this ethical conflict. At the same time, our proposal respects the interests of pharmaceutical research agencies and Catholic moral precepts, and fully abides by regulatory guidance.

Ethical evasion or happenstance and hubris? The U.S. Public Health Service STD Inoculation Study.

It's tempting to explain the Guatemala STD inoculation study as an attempt to evade the strictures of U.S research ethics. In fact, the researchers appear to have had benign reasons for going abroad. Only after they reached Guatemala did the study fly out of control.

Healthy volunteer registries and ethical research principles.

The dual enrolling of phase I volunteers is a potential risk to subjects. It can also distort study results, threaten study validity, and possibly cause harm to future patients. Existing subject registries differ in structure, funding, and governance. Although the choice of the ideal system is driven by the scope of the risk and the funding mechanism, and is ultimately a value judgment of freedom versus paternalism, none of the registries significantly impinges on the tenets of ethically based research.

Patterns of biomedical science production in a sub-Saharan research center.

BACKGROUND: Research activities in sub-Saharan Africa may be limited to delegated tasks due to the strong control from Western collaborators, which could lead to scientific production of little value in terms of its impact on social and economic innovation in less developed areas. However, the current contexts of international biomedical research including the development of public-private partnerships and research institutions in Africa suggest that scientific activities are growing in sub-Saharan Africa. This study aims to describe the patterns of clinical research activities at a sub-Saharan biomedical research center. METHODS: In-depth interviews were conducted with a core group of researchers at the Medical Research Unit of the Albert Schweitzer Hospital from June 2009 to February 2010 in Lambaréné, Gabon. Scientific activities running at the MRU as well as the implementation of ethical and regulatory standards were covered by the interview sessions. RESULTS: The framework of clinical research includes transnational studies and research initiated locally. In transnational collaborations, a sub-Saharan research institution may be limited to producing confirmatory and late-stage data with little impact on economic and social innovation. However, ethical and regulatory guidelines are being implemented taking into consideration the local contexts. Similarly, the scientific content of studies designed by researchers at the MRU, if local needs are taken into account, may potentially contribute to a scientific production with long-term value on social and economic innovation in sub-Saharan Africa. CONCLUSION: Further research questions and methods in social sciences should comprehensively address the construction of scientific content with the social, economic and cultural contexts surrounding research activities.

Barriers to enrollment in inflammatory bowel disease randomized controlled trials: an investigation of patient perspectives.

BACKGROUND: Despite a sizeable inflammatory bowel disease (IBD) population in the United States, large trials in IBD have difficulty recruiting patients. Reasons for low enrollment are uncertain. Our objective was to investigate specific barriers to enrollment in clinical trials by determining aspects of study design, disease state, demographics, and previous experiences with research that influence a patient's willingness to participate. METHODS: Patients with Crohn's disease (CD) and ulcerative colitis (UC) at the Massachusetts General Hospital Crohn's and Colitis Center were surveyed. RESULTS: Most participants (61%) had participated in some clinical research previously, although 50% of those were not interested in participating in a future study. Frequent doctor visits (69%), requirement of colonoscopy (55%), or sigmoidoscopy (49%), and blinding (46%) were the biggest deterrent study requirements. With each addition of one of these components, potential enrollment fell from 43.2% (86) to 14.6% (29) interested patients. Respondents were likely to participate in studies that were open label (60%), initially randomized then open label (57.6%), or saw the same doctor (52.5%). Among those disinclined to participate, strategies to boost enrollment included monetary compensation, an open-label component, or providing the same doctor at each visit. Men and patients who were currently flaring were more likely to participate. CONCLUSIONS: Elements of study design negatively and positively influence willingness to participate. Invasive procedures, randomization, and frequent visits negatively influenced willingness to participate and as each of these components are added, a significant additive percent of potential subjects are lost. Strategies to further identify barriers to enrollment within IBD study populations should be pursued.

Group recruitment sessions enhance patient understanding in a small multi-centre phase III clinical trial.

INTRODUCTION: There is continuing concern that patient information leaflets, tailored to current regulatory requirements, fail to meet patients' needs. Provision of comprehensible information is vital if patients are to provide valid informed consent. The design of the ARIX (acupuncture for radiation induced xerostomia) trial provided an opportunity to deliver researcher led, enhanced patient information to groups of potential participants. METHODS: Between November 2009 and September 2010, 149 patients attended a trial introduction meeting at their local site. All meetings followed the same format. The study coordinator delivered a PowerPoint presentation containing standard trial information together with customised local details. This was followed by group questions and answers. Patients could sign a consent form immediately afterwards or with local staff at a later date. Participants who completed the study were invited to feedback their views on these meetings. RESULTS: One hundred and forty nine patients attended a meeting of whom 116 ultimately participated in ARIX and provided feedback. Eighty four (72%) reported that the meeting helped their understanding of the trial 'very much'. Fourteen attendees reported feeling uncomfortable at having the information presented in a group setting but of these, only one felt under pressure to join the trial. Eighty three patients (71%) felt 'not at all' uncomfortable and 111 (95%) 'not at all' under pressure to participate. CONCLUSION: Trial introduction meetings involving researcher led presentation of information, followed by group discussion, can help enhance the information provided in the patient information leaflet in a useful and non coercive manner.

The fair transaction model of informed consent: an alternative to autonomous authorization.

The doctrine of informed consent in bioethics has relied on the view that consent is valid when it represents a patient or research subject's autonomous authorization. In this article we challenge this reigning conception of the validity of informed consent in clinical research, focusing in particular on the problem of the therapeutic misconception. We argue that the autonomous authorization model of informed consent suffers from four defects: (1) it fails to do justice to the relevance of risk-benefit considerations in shaping the criteria for the validity of consent, (2) it compromises the interests of subjects by preventing them from consenting to research participation with less than substantial understanding when doing so would likely be consistent with their preferences and beneficial to them or at least be unlikely to cause them harm, (3) it jeopardizes the interests of investigators by denying them fair notice regarding when the consent of research subjects can be considered valid and thus make it permissible for them to be enrolled in research, and (4) it threatens the reasonable limits on the responsibility of investigators to assure the adequacy of subjects' understanding of what research participation involves. In place of the autonomous authorization model, we present and defend a fair transaction model of informed consent, which better reflects the values served by consent.

Healthy volunteers for bioequivalence trials: predictive factors for enrollment failures--a case-control study.

OBJECTIVE: To identify social predictors for enrollment failures of healthy volunteers (hv) in bioequivalence trials. METHODS: Retrospective case-control study. Data was collected from clinical files of hv recruited in 13 bioequivalence trials approved by an independent IRB and local regulatory authority carried out between January and December 2009 at a Pharmacokinetic Unit in Buenos Aires, Argentina. All hv signed the Inform Consent Form. Only subjects who fulfilled all inclusion criteria required by the protocols were studied. Cases (enrollment failures): hv who fulfilled the protocols eligibility criteria but were not enrolled in the trials by their own decision. CONTROLS: hv who fulfilled all the protocols eligibility criteria and were enrolled. Cases and controls were matched by demographic/ physical data and compared in relation to database contact, unemployment, alcoholic/ drug family environment, history of alcohol/ drug abuse, and other social variables. Chi2-test and t-test were used to compare data; variables presenting statistical difference were included in a logistic regression model. RESULTS: A sample of 375 hv. was analyzed. cases: 81/375(21.60%). Controls: 294/375 (78.40%). Cases did not differ from controls in relation to nationality, educational level, length of study and history of alcohol abuse. Statistical differences between cases and controls were found in non-database contact, unemployment, alcoholic environment, drug abuse environment and personal history of drug abuse. In a multivariate analysis only unemployment, (OR: 4.20, p < 0.001), non-database contact, (OR: 2.35, p = 0.004) and alcoholic environment, (OR: 1.94, p = 0.045) remained as predictive factors. CONCLUSION: In bioequivalence trials, an unemployment condition, and an alcoholic family environment were identified as negative predictors for effective enrollment in new healthy volunteers.

Barriers to enrollment in non-small cell lung cancer therapeutic clinical trials.

INTRODUCTION: Despite recent advances in treatment, lung cancer remains the leading cause of cancer-related mortality in the United States. Therefore, there is a strong need for developing clinical trials in lung cancer therapeutics. Only a small fraction of patients with lung cancer are enrolled in clinical trials. It is critical to understand the barriers to participation in lung cancer clinical trials. METHODS: We reviewed the outpatient charts of consecutive patients with non-small cell lung cancer who presented for initial evaluation or consultation for further therapeutic management to the thoracic medical oncology group at the Alvin J. Siteman Cancer Center between January 1, 2006, and December 31, 2006. Available and appropriate clinical trials specific to the histologic subtype and stage were presented to the patients routinely, and reasons for nonenrollment were documented. We collected information on age, gender, ethnicity, histology, stage, performance status (PS), and insurance status. RESULTS: During the study period, 263 patients with non-small cell lung cancer were identified for the study. After initial screening, 183 patients had clinical trials available, which were appropriate for their diagnosis and stage of disease. One hundred one patients (55.2%) were ineligible for enrollment in a clinical trial. The most common reasons for ineligibility were poor PS (18%), need for emergent radiation (12%), lack of adequate staging information (6%), and comorbid conditions (4.9%). Despite being eligible for participation, 57 patients (31.1%) did not enroll in a clinical trial. Patient refusal accounted for 8.7%. The problems with transportation and distance from the medical center were reasons given for nonparticipation by 7.1%. Eleven patients (6%) did not participate in a clinical trial because of insurance issues. Ultimately, 25 patients (13.7%) were enrolled in a clinical trial. CONCLUSIONS: Poor PS, the need for emergent radiation, and patient refusal were the most common reasons for not participating in a clinical trial.