Balancing Ethics and Incentives: A Deep Dive into Clinical Trial Compensation Guidelines: Review Article

1.1 Overview of Compensation in Clinical Trials

Compensating research subjects in clinical trials is a long-standing practice. There is considerable documentation regarding investigators providing monetary incentives to their participants. A notable early instance involves Dr. William Beaumont, who in the early 18th century paid his patient, St. Martin Alexis, to conduct studies on gastric juice and the physiology of digestion, based on a mutual agreement that permitted Dr. Beaumont to perform research on him [1]. Compensation in research serves primarily two purposes: to compensate participants for their involvement in clinical trials and to address injuries related to the trial. This practice often raises ethical concerns regarding its potential impact on the integrity of clinical research. So, what motivates the provision of compensation in research? The literature indicates that compensation is offered for several reasons, including alleviating the financial burden on participants, acknowledging their contributions to medical science, ensuring adequate recruitment numbers within a specified timeframe, and reaching targeted populations that may be difficult to access or limited in number, such as individuals with rare conditions or from specific racial groups [2, 3]. Additionally, compensation is provided for any injuries related to the trial. Research participants in clinical trials receive compensation through both monetary and non-monetary means. Monetary compensation may be provided for the time and effort required for their participation or reimbursed for expenses such as travel costs and lost wages. Additionally, subjects receive free medical care for any injuries or harm incurred during the trial, and in cases of serious trial-related injuries, they are compensated financially alongside the provision of free medical treatment [4]. In 2004, the global clinical research industry began focusing on India as a "hub of clinical research" due to the availability of a large participant pool. Since then, the Government of India has sought to modify regulations, including the adoption of internationally recognized ethical and scientific quality standards known as Good Clinical Practice (GCP) to promote clinical trials. These policy changes have attracted various international Clinical Research Organizations (CROs) to expand their operations in India. India now hosts nearly a fifth of global clinical trials, offering significant financial and scientific potential [5, 6]. CROs benefit from a large pool of patients, skilled medical investigators, lower drug development costs, and the timely completion of clinical trials [7, 8, 9]. Affordable labour, low recruitment expenses, and reduced compensation rates for injuries or deaths during research drive the low cost of drug development in India. In many cases, CROs even recruit participants without formal guarantees of compensation, as many trial participants, being illiterate, are enticed by offers of free healthcare and financial incentives without being properly informed about the benefits and risks of the treatment [10]. The Indian government's efforts to promote clinical research have been widely appreciated, but inadequate regulatory guidelines have raised significant concerns. International media has highlighted cases of unethical clinical trials in India, where participants were not adequately compensated for injuries or fatalities. Additionally, flaws in the informed consent process and the absence of clear guidelines for compensation have become pressing issues for trial participants [11].

1.2 Ethical Considerations in Compensation Practices

Global norms and ethical standards for clinical research recommend providing compensation to volunteers who suffer research-related injuries [12, 13]. However, data on the frequency of compensation claims and the rate at which they are granted has been sparsely and inadequately reported here are the key ethical considerations in compensation practices for clinical research Fig.1 [14]. In most developed nations, civil law provides citizens with the right to claim compensation for harm caused by negligence, requiring the claimant to prove both negligence and a causal link between the cause and the damage. In countries with a comprehensive no-fault compensation system in healthcare, patients do not need to prove causality to receive compensation; however, this may limit their ability to claim negligence liability. In countries without a broad no-fault compensation system, specific laws may establish frameworks for compensation in particular areas [15].          

2. Historical Context of Compensation in Clinical Trials

Drug production, sales, clinical trials, import, and export in India are governed by the central government via the Central Drug Standard Control Organization (CDSCO), which is housed inside the Ministry of Health and Family Welfare. To make clinical research in India more uniform, in order to get safe and efficient medications into the market, the CDSCO develops standards and regulations for medications, diagnostics, and devices; updates regulations by changing acts and rules; and controls the marketing authorization of new medications [28].
India's history of drug control dates back to the British Empire, when the majority of pharmaceuticals were imported. According to Najmi et al. (2013), a significant number of illicit foreign drug makers oversupplied the Indian market with counterfeit and contaminated drugs in the first ten years of the 20th century. Consequently, a drug investigation panel was established by the government, and its recommendations were subsequently submitted as the drug bill for consideration in the legislative assembly. This bill ultimately evolved into the Drugs and Cosmetics Act of 1940 and the Drugs and Cosmetics Rules of 1945 [28]. These laws are the cornerstones that govern the importation, production, distribution, and retailing of pharmaceuticals and cosmetics in India.  Additionally, they established the Office of Drugs Controller General India (DCGI) and the Central Drug Standard Control Organization (CDSCO), both of which are part of the Ministry of Health and Family Welfare. The government agency that authorizes the administration of new medications to human participants in clinical trials carried out inside the nation is the DCGI [28]. Clinical trial compensation's ethical underpinnings trace their origin to some key historical events. The Nuremberg Trials (1945–1946), which revealed abuses during human experiments in Nazi Germany, gave rise to the Nuremberg Code (1947) a foundational document of contemporary bioethics that prioritized informed consent and the duty not to inflict unnecessary suffering in research. The Tuskegee Syphilis study (1932-1972) in United States represents a serious ethical concern, in this, African Americanmen with syphilis were not aware about the disease and not provided with a proper treatment, even when treatment is available and they did not even provide full consent to take part in the study which leads to public outrage and further several changes were in made in U.S. research policy, including Belmont Report (1979).These global events led to the integrations of ethical principals in clinical triasl governance and compensation framework.

Table 1: Historical events leading to development of compensation guidelines

2.1 Landmark Cases and Guidelines

Table 2 presents a compilation of landmark legal cases that have significantly contributed to shaping compensation guidelines in clinical research and drug-related adverse events. These cases have set legal precedents and influenced regulatory frameworks, ensuring ethical responsibility and fair compensation for affected individuals.

Table no 2: Landmark cases responsible for developing compensation guidelines

3. Types of Compensation in Clinical Trials

Clinical trials include different types of compensations to ensure and safeguard the participants. These may be incentives for participation, compensation for research-associated medical expenses, and time travel expenses [1]. It is necessary to understand the difference between incentives and compensation in clinical research because they serve different purposes and have different ethical considerations. Incentives are offered to subjects in clinical trial to encourage and motivate them for participants; this may include money, gifts or other benefits given subjects before or during recruitment. Whereas compensation refers to payment or benefits provided to participants for their times, efforts, inconvenience or harm suffered by them during the clinical trial. It may include reimbursement for travel or treatment for any injury caused by trail. The key difference between legal obligations and ethical responsibilities when it comes to compensating the subjects participated during the clinical trials. A legal obligation refers when laws or regulations require sponsors or researchers to compensate participants in cases of trial-related injury or death which is enforceable by law. There is also a key distinction between legal obligations and ethical responsibilities when it comes to compensating trial participants. Ethical responsibility means even if no physical harm occur participants still face inconveniences such as frequent travelling or loss in wages. Ethically researchers should provide compensation for these burdens even if not legally required.

3.1 Incentives for Participation

An incentive for participation in clinical research means any kind of compensation that is offered to any person in order to participate in the research. This may include:

Financial Compensation: Remunerations that involve using the money to meet costs or compensate the participants.

Reimbursement: including expenses of participants, for instance, transportation, or days without working.

Appreciation: Small tokens of appreciation for participation in medical research which will encourage people to participate in research [38].

3.2 Monetary Compensation: 

Monetary compensation refers to money in form of cash, gift vouchers or any form of material reward offered to participants in exchange for their time or input in research or any work-related undertaking.

- Unconditional incentives: These are given at the beginning of the study regardless of whether the task is completed or not [39]

- Conditional Incentive: These are offered only at the end of study. Participant may be told that they will be paid or given something of value after they complete the participation [40].

1. 1. 1. Non-Monetary Compensation

They are compensation rendered to participants in clinical research which do not involve direct financial payment.

- Recognition and Appreciation: Participants are most likely to appreciate that their effort has been valued through providing certificates or public recognition.

- Access to Healthcare Services: The participants may be offered free medical examination, treatment or further care as part of the trial.

- Educational Opportunities: Offering participants educational seminars or training about their health issues can help them and improve their knowledge of the study [41].

3.3. Availability of health and medical insurance during the clinical trials

Health and medical insurance during clinical trials can be available or not available in large differences. Not all clinical trials offer health insurance for participants; permit could contain insurance plans as well. This can vary depending on the type of study and trial, the organization that sponsors that trial, and agreements between the researcher and participants [42].

1. 1. 1. Medical Care:

Clinical research participants require medical care that includes support services from the time they enroll in the study until they complete their participation in the trial. The process starts where patients undergo first level of screening and health review in order to determine their health status and qualification [43]. The participants are followed up during the trial and are offered any treatment that is part of the study and side effects or complications are closely managed. Participants also receive other routine check-ups for ailments that may not be part of the study and the research teams work closely with the participant’s general practitioners. Follow up care is then used to monitor any complications that may arise after the study is over [44].

3.3.2 Insurance Coverage:

Clinical trial insurance safeguards both the participants and the research institutions in course of the trials. Participants, in general, it provides for medical expenses incurred in relation to study incidents, injuries and treatment or follow-up care of injuries that may result from these incidents. The insurance also covers legal expenses and professional negligence of the research institutions [45]. Nevertheless, coverage is usually limited to conditions that have not manifested themselves prior to the policy’s effective date, noncompliance with treatment regimens, and cases that are reported after the policy period has elapsed. It is mandatory that all clinical trials ensure they have sufficient insurance which meet the local requirements and where there is no guideline, there must be proper documentation of insurance offered and the procedures used in settling insurance claims [46].

4. Regulatory Guidelines on Compensation

4.1 Declaration of Helsinki 

The Declaration of Helsinki, which prioritizes participant protection, serves as the first set of guidelines for safeguarding the rights of human subjects taking part in scientific research. This necessitates that a researcher independently prioritize participant interests over research findings and follow international ethics in spite of national licenses. Respect for human subjects, participants' voluntary involvement, and a minimum risk guarantee are the Declaration's main tenets. This was modified in 2013, when the document's format was updated and additional clauses were included. Particularly noteworthy is paragraph 15, which requires participants' caregivers to offer appropriate recompense and care in the event that the research causes harm to the participants [47]. Regarding this provision, it may be said that the researchers are morally accountable for the participants' safety. It demands that any negative consequences resulting from involvement be appropriately addressed and justified. Additionally, it offers crucial details for reinforcing accountability in research endeavors. The inclusion of ethical considerations in research guarantees that the scientific community is upholding its integrity and building confidence at the same time. Through appropriate commitment to ethical norms that promote the sheer growth of knowledge and public health, residents have been protected, and the validity of the study findings has been improved [48].

4.2 ICH guidelines:

International Council for Harmonisation (ICH) guidelines share the highest level of commitment towards bringing about and adhering to ethical and quality-based clinical trials. These guidelines are most applicable when thinking about payment for the participants. ICH-GCP guidelines relating to compensation are particularly clear and state that such information should be disclosed. Subjects have to be aware of any compensation they may get so that the contribution decision was made without undue influence of the provided incentives. It should be an amount that is reasonable to offer to the participant in relation to time spent, inconvenience, and other risks incurred in participating in the trial. On this basis, ICH guidelines harmonize indemnity arrangements amongst member countries to support international clinical trials. These guidelines reduce the chances of differential treatment of participants, which may be occasioned by the differing standards in various countries [49].

4.3 CIOMS Guidelines and Implementation Challenges

Council for International Organizations of Medical Sciences (CIOMS) in collaborations with World Health Organizations (WHO) have developed international ethical guidelines for research involving humans. The recent version of CIOMS guidelines 2016 includes provisions on compensation for research related harm. The CIOMS guidelines are powerful in low income and middle-income countries, where the national regulatory framework is underdeveloped. These guidelines highlight the ethical obligation to compensate subjects for research related harm and recommend clear procedures for compensation especially among the vulnerable population.

5. Factors Influencing Compensation

The compensation structure in clinical trials directly reflects three key factors: trial phase, risk, and study difficulty. Providing compensation in clinical trials depends upon phase, complexity and risk involved in the study.

5.1 Risk-Benefit Analysis

The level of risk in clinical trials has a direct impact on the compensation that participants receive; therefore higher-risk studies usually compensate more. When vulnerable participants—like children or people with mental disabilities—are included, it presents an ethical conundrum since their choices are unfairly impacted by financial incentives [50].

1. 2. Trial Phase and Study Design

5.2.1 Early phase testing

Since early-phase studies are the first to test a novel medication or treatment on humans, they usually provide the highest compensation. This higher compensation recognizes the increased risks and challenges that participants encounter as pioneers in the testing of new medicines [51].

5.2.2 Later Stage Testing

As trials progress to later phases, compensation generally decreases. This reduction reflects the increased safety knowledge gained from earlier testing phases, resulting in lower risk for participants. By this stage, researchers have a better understanding of the treatment's effects and potential side effects [52].

5.2.3 Complex Study Designs and Participant Commitment

•  Studies with complex designs-including those that:
•  Have multiple treatment groups
•  Involve frequent clinic visits
•  Require longer participation periods
•  Involve more complex medical procedures [53].

5.3 Vulnerable Populations (e.g., children, elderly, pregnant women)

5.3.1 Vulnerable populations

The vulnerable population which includes economically disadvantaged individuals, enrolling in clinical trials primarily for financial gain. This is a concern regarding undue inducement, in which the prospect of payment can compromise voluntary consent. This form of inducement ethically undermines the participant's capacity to balance risks equally, especially when economic need is immediate. It is important that compensation arrangements for these groups are critically examined by ethics committees to make certain that rewards do not overwhelm voluntary, informed participation.

5.3.2 Children

Compensation to children in clinical trials should be reasonable compared to their age, comprehension level, phase/location/difficulty of the trial, and the duration of the trial. The compensation should also be in a ratio to the risk level to avoid bias. All the parents/guardians as well as capable child have to give their informed consent. Off-label compensation includes monetary compensation for time, fees for services rendered and reimbursement for out of pocket expenses and gifts. Perhaps it’s here where it is extremely important that compensation guidelines should be clear and free from ethical dilemmas, and invariable, be sensitive to the child’s dignity and/or his/her autonomy [54].

5.3.3 Elderly Individuals

The regulatory bodies should set the standard of how to compensate elderly patient who participates in clinical trial in case they suffer or develop some complications throughout the process. The development of compensation guidelines should also cover the certain risks of geriatric patients as they have different pharmacokinetics and pharmacodynamics and are at a higher risk of adverse effects [55].

5.3.4 Pregnant Women

Pregnant women being involved in clinical trial must undergone thorough risk assessment in order to provide protection to the both mother and the foetus. From the above participation, women should be given definite informed consent about the consequences, which may affect the maternal and foetal health. These must be made available in the research protocol in form; medical treatment, and the cost of managing complications associated with the trial [56].

5.4 Medical Compensation:

• Provide free medical services for any accident during the trial (the mother and the fetus).
• Medical expenses amounted to pregnancy complications associated with the trial
• Consideration of both short term and long-term impacts for the mother and the baby.
• Prenatal care if any special medical procedure or intervention is needed during pregnancy it should be carefully planned [57].

5.5 Financial Support:

• Regular compensation for trial participation
• Travel and accommodation reimbursement
• Loss of wages coverage during trial visits
• Additional expenses related to pregnancy care

5.6 Participant diversity

Clinical trials are increasingly adopting ethical strategies for the recruitment of underrepresented groups such as women’s, low-income populations and minority population to ensure fairness and scientific accuracy. This includes outreaching to the communities, working with local groups, accessible trial locations. It is also important to consider intersectionality-how factors such as gender, race and socioeconomic status increase vulnerability to exploitation. Identifying these layers assists researchers in planning recruitment and compensation protocols that are respectful, ethical, and inclusive.

5.7 Comparative approaches to compensation globally

The compensation in clinical trials is practice vary widely across countries such as in U.S., compensation in case of injury is not guaranteed it depends upon on institutional policy. But in India, it is the responsibility of sponsors for compensating the subject in case of trial related injury under Schedule Y and ICMR guidelines. European union follows a hybrid model for compensation in clinical trials with no fault insurance frameworks in many countries. Additionally, ethical standards like CIOMS in collaboration with WHO recommend clear and equitable compensation, especially in low- and middle-income countries.

6. Ethical Challenges and Controversies

Some of the issues that ethical consideration and controversies in compensation of clinical trials involve include the following. Identifying an appropriate rate of compensation is important, as recommended remunerations could encourage engagement too much for monetary gains and not for interest, which might alter a study’s outcomes in that it could encourage people to participate primarily for money [58].  On the other hand, the non-provision of any remuneration could be exploitative rather than genuine interest, potentially skewing results. Conversely, inadequate compensation could be exploitative. Particularly, payment transparency and payment voluntariness: it must never be the case that employees did not understand the terms of compensation and then decided to join; changes to compensations also should be agreed upon. Financial self-interest is admissible nonetheless; it should not force a people into participation and subsequently guarantee its voluntary nature [59].

6.1 Overcompensation and undue influence

It thus remains important for continuing discourse within the research community regarding such matters as overcompensation and undue influence. The authors can only commit to proactive endeavours whereby the compensation applies to the highest ethical standards, thus protecting the dignity of the individuals participating in the research [60]. Sustaining this ethical balance is imperative for the defense of clinical trials dignity and accuracy.

Information sharing and consent overcompensation and undue influence necessitate ongoing debate and discussion within the research community [61]. Researchers must engage in proactive efforts to address these complexities, ensuring that compensation practices align with the highest ethical standards and respect the dignity of all individuals involved in the research process. Maintaining this ethical equilibrium is crucial to upholding the integrity and credibility of clinical trials [62].

6.2 Transparency and informed consent

The ethical research of humans demands researchers to obtain informed consent from participants and provide them fair compensation. The principles serve two essential functions that support trust development and research integrity preservation as well as participant right protection. Informed consent requires researchers to provide complete research information involving advantages along with drawbacks to participants before they give voluntary permission. Valid ethical frameworks like Good Clinical Practice (GCP) guidelines together with Declaration of Helsinki serve as guides to create openness between scientists and their research subjects [63]. Research participants need informed consent together with complete disclosure about compensation from both a legal and ethical perspective. Potential research subjects need to receive complete information about compensation terms before making their decision. Ethical, transparent payment procedures help researchers show participants respect when they distribute burdens fairly with benefits equitably [64].

6.3 Compensation in Developing Countries

There is, however, a need to establish how to pay participants in clinical trials, especially in developing countries. The creators need to be careful about such a phenomenon during an economic recession [65]. Paying should therefore follow local income comparability instead of global comparability so as to maintain stability in local markets. It is therefore important to involve the community in coming up with the right pay structures. Voluntary informed consent of applicants must also be secured at all times. The contents that are useful to communicate about compensation should be advised, reported, and disseminated and free from pressure. It’s important to gain community input in the specific compensation methodologies that can or cannot be considered culturally appropriate [66]. The trial's participants have a moral responsibility to minimize any possible adverse effects and ensure that patients will continue to get such valuable treatment once the experimental phase is over. It implies that the compensation structure ought to incorporate these clauses. The duty of overseeing the ethical conduct of clinical research, including the compensation structure of clinical trials, falls on ethics review committees at the national and regional levels [67].

6.4 Role of Institutional review boards and Ethics committee

Institutional Review Boards (IRBs) or Ethics Committees plays a significant role in providing compensation in clinical trials is fair and ethically appropriate. Thee IRBs review informed consent forms, assesses the risk benefit ratio of clinical study and ensure that payment does not unduly influence the participation of subjects especially among vulnerable groups. The global guidelines such as CIOMS and ICH-GCP emphasize their responsibility in preventing exploitation, it is important to strengthening the IRB capacity through training and transparent decision making which improve ethical oversight and protect participant rights.

7. Best Practices for Compensation in Clinical Trials

Compensating the participants is one of the most essential points of clinical trial protocols since it establishes relationships between investigators and participants. Establishing the correct pay model, however, is not always an easy process. The decision-makers in clinical trial teams have to consider many factors, some of which include minimum wage rates, time and effort of the participant, risk or burden exposure, economic factors at the local level, and others. Inability to conclude on reasonable pay results in problems with the engagement of participants and with retention and possible regulatory problems [68]. That is why it is possible to recommend the following recommendations for clinical trial organizers: In this way, clinical trial organizers can create compensation plans that are fair and reasonable, competitive, and attractive to the participants, making the overall research efforts successful [69].

7.1 Determining Fair Compensation

It is important to avoid their exploitation during trials and ensure that compensation fairly represents their effort to increase diverse trial participation rates. Lack of economic incentives to seek preventive services is one reason why Cash-Poor, Health-Insurance Poor individuals do not enroll; it costs money to participate. This is especially unfair to minority persons, as race, ethnicity, and gender are terribly tied to poverty levels. Although there are apprehensions with an aim to figure out the payment biasing the decision-making process, the ethical advancement is to make sure that participants are not financially worse off. This implies that fair pay practitioners should capture costs and time used because inadequate payments are perceived as unfair if the effects are differential. More so, the stakeholders need to ensure that through their payment schedules they do not encourage institutional enrollment. This can include promising a high starting salary, awarding step or stair bonuses for study advancement, achieving a COA, as well as adopting comodalities such as transport or food [70]. The time involves the projection of participant motivation, study practicality, and ethical issues over the course of long-term clinical trials and observational trials. In conclusion, a part of research compensation practice involves considerations of the ability of participants to afford to work in clinical research, their pay structure to reflect fairness, and that payment issues raise questions of diversity and inclusion. With such information, the stakeholders can make clinical trial enrollment more diverse and less exclusive [71].

7.2 Balancing risk, time, and effort

A variety of methods or strategies is the key moment when it is possible to maintain a fair balance of the risks with the time and efforts and guarantee the participant safety and the ethical elements of clinical research. Subjects are at risk of experiencing some unwanted effects from investigational products, and this information must be disclosed prior to signing a consent form for the study. In light of the multiple visits and assessments that are required, the benefits that come with it have to be balanced. Engagement, for example, in the form of protocol implementation and filling in of questionnaires, is differential in intensity and should take into account the situation with the participant [72]. Whenever they are compensated fairly, they do not feel compromised to act in a particular way, putting much influence on decision-making. Redressing these factors leads to better participants’ enrollment and the study’s general attrition, which is very important as the research goals are achieved. In this case, the management of participant expectation should involve: is essential for ensuring participant safety and ethical integrity in clinical research [73]. Participants face potential adverse effects from investigational products, which must be clearly communicated during informed consent. The time commitment, involving multiple visits and assessments, must be weighed against potential benefits. The effort required, such as adhering to protocols and completing questionnaires, varies and should consider participants' personal circumstances. Fair compensation mitigates the perceived burden, encouraging diverse involvement without undue influence on decision-making. Addressing these factors enhances participant recruitment and retention, fostering an inclusive research environment that benefits all stakeholders [71, 74].

7.3 Managing participant expectations

Expectations of compensation in clinical trial participant management involve understanding the signs of communication beforehand and being concise and clear. Give clear and comprehensive written information on payment terms and frequency and payment type in the recruitment information materials and consent forms and statements. A developed payment schedule that itemizes remuneration rates by study activities, actions in the instance of missed visits, early withdrawal, and reimbursement for expenses. Appoint people to answer questions about compensation and keep records of payment. Continuing to provide participants with updates on earned compensation and addressing their concerns where necessary enhances their trust and satisfaction level. Make sure all the members of the study team speak with one voice, and make it a practice to keep record of all communications and transactions on compensation [4]. Compensation is a key element for participants’ retention in clinical studies. Monetary payment and other reward strategies are used during clinical studies to   maintain participant retention.

8.  Monetary Payment:

Monetary incentive remains one of the most vital forms of motivating participants to remain involved throughout the clinical trial phases and actually influences the overall success of research and quality of results. It is therefore evident that properly developed compensation structures have worked well in sustaining credit from participants through controlling study costs as well [75]. The effect of financial incentives is two-pronged as it affects the retention on different aspects. Firstly, it has a function of acknowledging participants’ commitment and time offered, which is real incentive towards continued participation. Furthermore, apparently attractive reward schemes extended for most participant’s working conditions makes such plans particularly appealing to participants when they are designed to favour individual participant’s conditions. However, the ability of the researchers to gather data regarding participant traits and motivations is crucial for such strategic compensation approaches [73].

8.1.  Impact of Compensation on Recruitment

Compensation will significantly impact participants' enrolment in clinical trials and the factors influencing this process. Encouragement of participants and acknowledging their contributions are the main benefits; yet, potential bias and participant exploitation are ethical drawbacks. It is a complex matter to make sure that workers receive adequate compensation while also attempting to determine what is reasonable and appropriate for a certain firm [77]. Participant scope might also be influenced by ideas on compensation. Such reimbursement schemes require to be regularly re-assessed to ensure that the compensations are always reasonable, ethical, and consistent with participants' needs Figure 2. Also important for transparency is trial risk and benefit information in respect to enabling participants to give valid consent and preserve clinical research integrity [75, 77].