Ethical Checklists for Clinical Research Projects and Laboratory Medicine: two tools to evaluate compliance with bioethical principles in different settings

Research design and planning

The checklist for research studies prompts a meticulous examination of ethical considerations. Respect for the people and their autonomy are at the forefront in terms of participant values and obtaining informed consent is mandatory (E-CRP 2a(i)) [18]. Study participants must sign an informed consent that describes the most important elements of the protocol and ensures data privacy and confidentiality. It must explain in simple terms the purpose of the research, the risks and benefits of participation and the right to withdraw oneself from the study without any negative consequences (E-CRP 2a(ii)). It is important to clearly define the study’s design given that a cross-sectional, longitudinal or interventional design will entail different impacts on the patient’s autonomy (E-CRP 2a(iii)). Research involving human subjects must be reviewed and approved by an IRB or its equivalent, which must approve of the research, monitor the progress regularly and approve of any proposed changes over the course of the investigation (E-CRP 2e(i)). Justice is achieved through unbiased or fair participant selection (E-CRP 2b(i)), with additional safeguards for vulnerable populations (E-CRP 2b(ii)). (*) Beneficence is quantified, considering potential benefits (E-CRP 2c(i)), while non-maleficence is made sure through steps to minimize potential harms (E-CRP 2d(i)), ensuring investigational product safety is monitored (E-CRP 2d(ii)) and health insurance is provided (E-CRP 2d(iii)). Laboratory tests should be appropriate and beneficial for the patients based on the best clinical evidence and they must be selected with the participation of a laboratory professional (E-CRP 2c(ii)). When research requires the use of patients as study subjects, it must be designed in order to minimize the risks and maximize the expected benefits. When animals are involved, their proper care must be guaranteed. Institutional Animal Ethics Committees should actively participate in these designs since the well-being of research animals is of utmost importance for biomedical research [19]. Moreover, the 3 Rs alternatives should be considered: (i) Reduction in the number of animals involved, (ii) Refinement of the techniques and procedures aimed at reducing pain or distress and (iii) Replacement of the use of live and conscious animals with other methods. Potential use of hazardous materials and the consequent need to guarantee laboratory safety are aspects that researchers should consider and review at least once a year (E-CRP 3d(iv)) [16].

Data collection and management

In the data collection phase, autonomy extends to data protection and privacy (E-CRP 3a(i & ii)). Justice is upheld through transparent data collection processes (E-CRP 3b(I & ii)), while beneficence ensures the quality and integrity of data obtained. Data must be collected according to state-of-the-art analytical and statistical techniques, results must be reported correctly, and the work of other researchers must be respected (E-CRP 3c(i & ii)). When using point of care testing (POCT), laboratory professionals are to control the performance and quality assurance of these systems (E-CRP 3c(iii)). When samples are submitted from outward laboratory facilities, collection and transportation protocols should be under the supervision of laboratory medicine professionals (E-CRP 3c(iv)). Non-maleficence includes procedures to monitor adverse events and minimize risks associated with data collection (E-CRP 3d(i–v)). Appropriate data treatment is a central issue for science. Non conducive data may be attributed to poor experimental design or inaccurate measurements. Beyond the errors that may occur in an investigation (honest errors), there are others caused by negligence (haste, carelessness, inattention, etc.). Researchers who act negligently put their own reputation, the work of their colleagues, and society’s trust in science at risk. If a researcher manipulates data, he or she is violating basic values and professional standards (E-CRP 3e(i)). To make progress, researchers must trust colleagues who have accomplished their work before them according to accepted standards. Research misconduct refers to such behavior that deviates from the central principles of science including fabrication, falsification and plagiarism when proposing, executing, reviewing or reporting results. These actions are seen as the worst violations of scientific standards, because they undermine the trust in which science is based on [16].

Analysis and dissemination

Researchers are accountable for communicating their work process and the generated knowledge might be useful to society. The most significant way to share a research paper is through peer-reviewed publications. In fact, peer reviews offer a fundamental and independent mechanism to evaluate and improve the quality of a scientific article. Publication of findings should also adhere to publication ethics which specify fair and just authorship practices and acknowledgment of other contributors [20].

The analysis and dissemination phase underscores autonomy in disseminating research findings while protecting participants’ privacy (E-CRP 4a(i)), in giving participants access to clear results (E-CRP 4a(ii)) and addressing them with sensitivity toward cultural norms and values (E-CRP 4a(iii)). Justice implies disclosing COI (E-CRP 4b(i)) and prioritizing open access (E-CRP 4b(ii)). Beneficence is accomplished by generating accurate and reliable results, giving study subjects access to benefits or treatments that could emerge from the investigation (E-CRP 4c(i & ii)) as well as providing evidence-based recommendations (E-CRP 4c(iii)); and non-maleficence examines potential risks during analysis and dissemination (E-CRP 4d(i & ii)). If a researcher publishes preliminary results that are later shown to be incorrect, much research could be lost and public trust could be jeopardized [16].

Pre-analytical phase

In the process of laboratory medicine, the pre-analytical phase sets the tone for ethical patient care. Patients’ confidentiality is of paramount importance in laboratory medicine (E-CLM 10). Patients have the right to know which laboratory test they are undergoing (E-CLM 11) and, in certain cases (HIV, genetic testing, invasive procedures for obtaining samples, etc.) a written informed consent is necessary and legally required (E-CLM 12–14) [18]. Patients also have the right to refuse testing (E-CLM 15). When samples are employed to perform tests without the patient’s knowledge and informed consent and an incidental finding emerges, laboratory medicine professionals must act accordingly and inform the reason why samples were subject to those tests and the associated results (E-CLM 16). Exceptions could also arise based on religious/ethnic grounds. Moreover, reflex/reflective testing should be contemplated through a broader informed consent [21]. Justice in sample collection and handling implies fairness, meaning prioritizing people in need (E-CLM 17). Laboratory medicine professionals have the moral obligation to be up-to-date on the development of new tests and their usefulness in each particular setting (E-CLM 18), and they must discuss with administrators the possibility of introducing them in routine clinical practice, if authorized by general insurance systems, wherever applicable (E-CLM 19–20). To avoid patients’ and samples’ identification errors two independent identifiers must be used (E-CLM 21 & 22). Sample collection through venipuncture and other fluid/tissue sampling procedures do minimize harm (E-CLM 23). The preanalytical phase also includes specimen handling, transportation and storage according to standardized operating procedures (E-CLM 24). Adverse events must be prevented and mitigated in case of its unfortunate occurrence (E-CLM 25–26) [14].

Analytical phase

Transitioning into the analytical phase, laboratory medicine sustains respect for patients’ autonomy, ensures confidentiality (E-CLM 27) and respects their right to decline testing despite samples having already been collected (E-CLM 28). Under no circumstance should any discrimination be allowed and samples should be given priority only when derived from emergencies (clinical urgency, critical results, etc.); no one should be given priority, unless medically indicated, and all individuals should be treated as equal (E-CLM 29). Turnaround times should be as quick as possible, without compromising the quality of the result (E-CLM 30). Beneficence is achieved via standardized procedures that assure the quality of results (E-CLM 31), the adoption of state-of-the-art methods and professional standards (E-CLM 32) recommended by scientific societies and through the participation in quality assurance programs (E-CLM 33); while non-maleficence is exemplified by refusing testing according to sample rejection criteria (hemolysis, lipemia, insufficient volume, stability, etc.) (E-CLM 34) or when instrumental deficiencies are detected (malfunctioning, inaccuracy, inappropriate regents, etc.) [14]. Notwithstanding, specimens like cerebrospinal or pleural fluid, among others, or in the case of surgical tissue submitted to the laboratory, deserve a special or unique treatment and the process employed to reject the samples may be less straightforward.

Post-analytical phase

Policies on samples as well as retention and disposal of medical records (E-CLM 35 & 36), procedures regarding authorized personnel (E-CLM 37)/patients’ relatives allowed to access medical records (E-CLM 38) and reliability and security of the methods to share laboratory results uphold autonomy (E-CLM 39). Regardless of payment status, test results should be delivered according to clinically useful turnaround times, especially in emergency situations (E-CLM 40). Beneficence is proved through middleware rules and auto-validation of test results based on AI [22, 23], laboratory reports that include essential patients’ information and relevant data allowing a clear and exhaustive interpretation of the results obtained (E-CLM 42), timely reporting of critical values (E-CLM 43) and adequate storage of samples after their analysis (E-CLM 41), in compliance with regulations; while non-maleficence is promoted through prompt and accurate (E-CLM 45) interpretation of test results by qualified personnel (E-CLM 44) and the notification of any error that might have occurred (E-CLM 46) [14]. Finally, it is highly recommended to keep records of instigating risk assessments, incident reporting, audits, training programs and quality assurance systems for proactive prevention of testing errors.