Informed Consent in Human Subjects Research: A Comparison of International and Saudi Arabian Guidelines

Full text

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J Clin Res Bioeth, Vol.14 Iss.6 No:1000475
Research Article
May M. Al-Madaney, Institute of Biomedical Ethics and History of Medicine, University of Zurich, Winterthurerstrasse 30,8006
Zurich, Switzerland, E-mail: may.al-madaney@ibme.uzh.ch; malmadaney@kfmc.med.sa
Received: 07-Nov-2023, Manuscript No. JCRB-23-23823; Editor assigned: 10-Nov-2023, Pre QC No. JCRB-23-23823 (PQ); Reviewed: 24-Nov-2023,
QC No. JCRB-23-23823; Revised: 01-Nov-2023, Manuscript No. JCRB-23-23823 (R); Published: 11-Dec-2023, DOI: 10.35248/2155-9627.23.14.475
Citation: Al-Madaney MM, Andorno R, Fassler M (2023) Informed Consent in Human Subjects Research: A Comparison of International and Saudi
Arabian Guidelines. J Clin Res Bioeth. 14:475.
Copyright: © 2023 Al-Madaney MM, et al. This is an open access article distributed under the terms of the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
OPEN ACCESS Freely available online
Informed Consent in Human Subjects Research: A Comparison of
International and Saudi Arabian Guidelines
May M. Al-Madaney1,2*, Roberto Andorno1, Margrit Fässler1
1Institute of Biomedical Ethics and History of Medicine, University of Zurich, Winterthurerstrasse 30,8006 Zurich, Switzerland;
2Research Center, King Fahad Medical City, Riyadh Second Health Cluster, P.O. Box. 59046, 11525 Riyadh, Kingdom of Saudi Arabia
ABSTRACT
Objective: Informed Consent (IC) is an essential requirement for the conduct of medical research involving
human subjects. Since the Nuremberg Code was adopted in the aftermath of the Second World War, various
international guidelines have specified the conditions for a valid IC for medical research. Among the most
relevant guidelines are the World Medical Association’s Declaration of Helsinki, the guidelines of the Council
of International Organization of Medical Sciences (CIOMS), and the Good Clinical Practice Guidelines of
the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use
(ICH-GCP). This paper aims to compare the above-mentioned international guidelines with Saudi Arabia’s
Law of Ethics of Research on Living Creatures regarding the requirements for IC. The comparison also includes
some relevant regional and domestic laws. The objective of the study is to determine whether the compared
regulations coincide regarding the requirements for a valid IC or whether they show significant differences,
and to what extent such requirements are also present in Saudi Arabia’s regulations.
Methods: We conducted a content comparative analysis of the above-mentioned guidelines regarding five
elements of IC: Disclosure, comprehension, voluntariness, competence, and form of consent. These five topics
were subdivided into 44 subtopics. Then we compared and critically analyzed their similarities and differences.
Results: The similarities and differences observed in the seven guidelines are summarized under the five
components of IC mentioned above and regarding 44 selected subtopics.
Conclusion: The analysis of the above-mentioned guidelines shows that while the most basic components
of IC are present in all the compared documents, there are some differences between them. Specifically, the
study found that the Saudi Arabian regulations include 26 of the 44 subtopics considered and that most of the
elements that are missing relate to the disclosure of information to participants.
Keywords: Informed consent; Medical research; Disclosure; Comprehension; Voluntariness; Competence;
International guidelines
ABBREVIATIONS
IC: Informed Consent; WMA: World Medical Association; DoH:
Declaration of Helsinki; CIOMS: Council for International
Organizations of Medical Sciences; WHO: World Health
Organization; ICH: International Council for Harmonization;
GCP: Guideline for Good Clinical Practice; ICH-GCP:
International Conference on Harmonization Good Clinical
Practice; HRA: Swiss Human Research Act; CFR: Code of Federal
Regulations; CHRB: Council of Europe’s Convention on Human
Rights and Biomedicine; KSA: Kingdom of Saudi Arabia; NCBE:
National Committee of Bioethics
INTRODUCTION
Obtaining Informed Consent (IC) from participants is an absolute
requirement when conducting clinical research, as mandated by
all major guidelines. The aim of IC is to ensure that individuals
*Correspondence to:

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make a free and informed decision about participating in a research
study. This process involves providing potential subjects with clear
and understandable details about the study, such as its purpose,
procedures, risks, benefits, and alternatives to participation.
This requirement arises from the ethical principle of respect for
individual autonomy and is formally recognized in international
human rights law [1,2].
Informed consent has been an axiom of clinical research and
practice since the end of the Second World War II. In 1947, the
military tribunal that sentenced the Nazi doctors who conducted
brutal experiments in concentration camps developed a set of ten
ethical principles for medical research, which is known since then
as the “Nuremberg Code”. In its first principle, the Nuremberg
Code provides that
• “The voluntary consent of the human subject is absolutely
essential. This means that the person involved should have legal
capacity to give consent; should be so situated as to be able to exercise
free power of choice, without the intervention of any element of
force, fraud, deceit, duress, overreaching, or other ulterior form of
constraint or coercion; and should have sufficient knowledge and
comprehension of the elements of the subject matter involved as to
enable him to make an understanding and enlightened decision”.
Since then, it has been widely accepted that obtaining research
participants' consent encompasses criteria of disclosure,
comprehension, voluntariness, and competence [3]. However,
because of its association with Nazi war crimes, the Nuremberg
Code had relatively little effect on the practice of medical research.
In 1964, the World Medical Association (WMA) decided to develop
a new set of ethical principles more directly focused on clinical
research than the Nuremberg Code. The outcome of those efforts
is the Declaration of Helsinki (DoH), which has been revised seven
times since its adoption in 1964, most recently in 2013 [4].
An entire section of the DoH (Paragraphs 25 to 32) is devoted to
informed consent, which clearly is one of the key components of
the document. According to Paragraph 26, potential subjects must
be adequately informed of the “aims, methods, sources of funding,
any possible conflicts of interest, institutional affiliations of the
researcher, the anticipated benefits and potential risks of the study
and the discomfort it may entail, post-study provisions and any
other relevant aspects of the study”. In addition, potential subjects
must be informed of their “right to refuse to participate in the study
or to withdraw consent to participate at any time without reprisal”.
The Council for International Organizations of Medical Sciences
(CIOMS), which is a non-governmental body associated with
the World Health Organization (WHO), is another important
organization in this field. Since 1982, it has been involved in the
development of international guidelines for medical research. In
2016, CIOMS replaced previous guidelines with the “International
Ethical Guidelines for Health-related Research Involving Humans”
[5]. This document includes 25 Guidelines on various aspects of
biomedical research. Informed consent is specifically addressed in
Guidelines 9 and 10.
Another international body involved in this area is the International
Council for Harmonization of Technical Requirements for
Pharmaceuticals for Human Use (ICH), which brings together
regulatory authorities and representatives of the pharmaceutical
industry and developed the Guideline for Good Clinical Practice
(GCP) in 1996. This guideline aims to ensure ethical and scientific
quality in designing, recording, and reporting trials that involve
human subjects, and that trial data are credible and reliable,
regardless of where in the world the trials have been conducted. In
2016, the GCP was updated by means of an addendum that provides
additional guidance [6]. The informed consent requirement of is
addressed in Paragraph 4.8 among the researcher’s responsibilities.
In parallel with the international organizations mentioned
above, several countries and regional organizations have adopted
regulations on biomedical research over the past few decades.
This paper examines three of them: The Swiss Human Research
Act (HRA) (2011); The US Code of Federal Regulations (CFR)
(Title 21, Section 50, and Title 45, Section 46); and the Council of
Europe’s Convention on Human Rights and Biomedicine (CHRB)
(1997), also known as “Oviedo Convention”. The inclusion of the
Swiss Human Research Act in the present analysis can be explained
by the circumstance that the study was conducted in Switzerland.
This study aims to compare the above-mentioned international,
regional, and national regulations with the Kingdom of Saudi
Arabia (KSA) Law of Ethics of Research on Living Creatures (2010)
(hereafter, “The Law”) with regard to the requirements for informed
consent for medical research. It must be noted that The Law was
established to monitor studies involving genetic material, human
parts, and living creatures without contravening Islamic laws. A
supplemental document, called “Implementing Regulations of
the Law of Ethics of Research on Living Creatures” (hereafter, the
Implementing Regulations), was later approved in 2011. The two
are used concurrently to protect research subjects from unethical
conduct. Besides, the KSA has a National Committee of Bioethics
(NCBE) that focuses specifically on the involvement of human
subjects in clinical trials [7]. Ultimately, the goal of this study is to
consider whether the Saudi guidelines provide sufficient protection
for the rights of research subjects regarding the informed consent
requirement.
To our knowledge, this is the first study to systematically compare
the requirements for informed consent in Saudi Arabia and
international and national regulations. In 2017, a study by the
bioethicist Ghiath Alahmad analyzed 10 guidelines on medical
research, including the ICH-GCP, CIOMS, and DoH’s, as well
as the guidelines from eight Arabic counties, including Saudi
Arabia. However, it was not focused on the specific elements of
informed consent [8]. Another comparative study by Alahmad et al.
concluded, in general, that the requirement of informed consent is
the only item mentioned in all the compared guidelines [9].
It must also be mentioned that, in order to ensure a truly informed
consent, it is vital to facilitate content comprehension by participants.
This explains the need for simplified versions of informed consent
documents. In some settings, such as in developing countries with
low levels of literacy, researchers may be particularly required to
explain the content of the IC form to participants. However, the
importance of such an explanation is critical for all participants
around the world, regardless of their educational achievements.
Interestingly, a study has shown that there is no direct correlation
between the educational achievements of research participants and
their comprehension abilities regarding the planned research [10].
In any case, guidelines for medical research have alwayes had the
difficult task of adapting basic ethical concepts to varied cultural
and social contexts and promoting education in research ethics.
Obviously, ethical research violations may occur in spite of policy
statements and guidelines on clinical trials [11].

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Scholar) with detailed information about a standard were used for
further analysis. Governmental websites, bioethics sites, and other
reputable sources were preferred for the identification of the right
content.
The next stage was to compare these seven guidelines and critically
analyze the similarities and differences between them regarding
the above-mentioned five components. The analysis focused on a
particular theme in one guideline and crosschecked its presence or
absence in the other guidelines. After completing one document,
the same process was repeated with the other regulations. Therefore,
there was no specific standard used as a baseline or a reference point
for the comparison analysis. This ensured that all common and
unique themes across all the guidelines were equally analyzed. The
critical analysis and evaluation of the highlighted components were
comprehensively displayed in a Table 2. The comparison (Table 2),
was filled out by two researchers (MM and MF). The meaning of
“not explicitly” is used to indicate that a broad or common notion
is referred to but not with the exact term. The Declaration of
Helsinki, for example, says that participants “must be adequately
informed of the methods” (Paragraph 26) [4]. However, the term
“methods” is too broad and would need more explanation. If
during the analysis the two researchers extracting the data disagreed
on a particular term, the original text was reviewed again, and the
dispute was resolved through discussion Table 2.
METHODOLOGY
In this study, the content analysis focused on five major components
of IC:
1. Disclosure
2. Comprehension
3. Voluntariness
4. Competence
5. Consent
The international standards selected for the analysis were the DoH,
CIOMS, and ICH-GCP [4-6]. The CHRB, the CFR, and the HRA
were chosen as the legal standards regulating human participant
research in developed countries, while the Implementing
Regulations are the national guidelines used in Saudi Arabia [7, 12-
14]. Table 1 shows which issuing bodies in which countries provide
guidelines.
As a first step, we identified the provisions dealing with IC in
the DoH, CIOMS, ICH-GCP, CHRB, CFR, HRA, and the
Saudi Implementing Regulations [4-7, 12-14]. Each standard was
identified through a direct online search using their respective
titles and initials. The search websites (PubMed, and Google
Table 1: Selected issuing bodies and their guidelines.
Country/
International Issuing year Last update year Guideline(s) Issuing body
International 1964 2013 Declaration of Helsinki (DoH) World Medical Association (WMA)
International 1982 2016
International Ethical Guidelines for
Biomedical Research Involving Human
Subjects
Council for International
Organizations of Medical Sciences
(CIOMS)
International 1995 2016
International Conference of Harmonization
Guidelines for Good Clinical Practice (ICH–
GCP)
International Conference on
Harmonization (ICH)
International/
Council of Europe 1997 2005 Convention on Human Rights and
Biomedicine (CHRB), Council of Europe Council of Europe
United States 2006 2023 Code of Federal Regulations (CFR) Federal Agencies
Switzerland 2011 2014 Human Research Act (HRA) The Federal Assembly of the Swiss
Confederation
Kingdom of Saudi
Arabia 2011 2022 Implementing Regulations of the Law of Ethics
of Research on Living Creatures.
National Committee of Bioethics
(NCBE)

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IC Components Informed consent elements DoH CIOMS GCP CHRB CFR HRA The Implementing
Regulations
Disclosure to
participants
The fact that this is scientific research + + + + + + +
Aims of the study + + + + + + +
Possible benefits and risks of the study intervention + + + + + + +
Trial–related injury treatment and/or compensation + + + + + + +
Right of the participant to withdraw the consent at any time
without receiving any drawbacks + + + + + + +
Record confidentiality for identifying information + + + + + + +
Research participation invitation – + – + + – +
Research title – + – – – – +
Methods of the study, e.g., randomization – + + – – – –
Duties and functions of the participants connected to the
study, including follow–up appointments + + + – – – +
Possible discomfort or burden + + + + + + –
Alternative interventions that are available outside the
research and their benefits and risks – + + – + – +
Different interventions of the study arms – + + – – – –
Trial participation payment as prorated (if any) – + + – – – –
The chance to receive a placebo intervention or no
intervention – – – – – – –
Blinding of the participant or the physician – + – – – – –
Ethics committee approval – + – – – – –
The existence of another study group that may receive
a seemingly more attractive intervention in the case the
participant was allocated to the control group
– – + – – – –
The fact that a new treatment can cause unwanted effects
that one cannot reliably predict, and which can harm the
participant
– – – – + – –
Sources of funding for the study + + – + – – –
Potential conflicts of interest + + – – – – –
Researchers’ institutional affiliations + + – – – – –
The name of the institution approving the research – – – – – – +
The contact person(s) for further information – – + – + – +
Informing participants of new findings that might affect their
willingness to participate in the research – + + + + – +
Receiving the results of the study + + – + + + –
Termination of participation without the subject's consent for
foreseeable reasons and/ or circumstances – ++ – + – –
The approximate number of subjects involved in the trial – – + – + – –
The trial participation duration – + + + + + +
The need for further details in the case of genetic research
and the possible future use of biological materials collected
during the research
+ + – + – + –
Comprehension
The information should be given in a language and at a level
of understanding appropriate to the research subject (The
informed consent document should be simplified as much as
possible)
+ + + – – – +
Comprehension verification through questions and
clarifications + + – – – – +
Table 2: Comparison of informed consent elements from different ethical guidelines.

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Voluntariness
Voluntariness of the participation/right of the participant to
refuse participation + + + + + – +
The physician must be particularly cautious if the potential
subject is in a dependent relationship with the physician or
may consent under duress
+ + + – – – +
Competence
Potential research subjects who are incapable of giving
informed consent (incompetent/vulnerable subjects and
minors): the physician must seek informed consent from the
legally authorized representative
+ + + + – + +
Formal
requirements of
consent
The informed consent in written format + + + + + + +
Signature of the human subject – + + – + – +
Before a decision on consent is made by the persons
concerned, they must be allowed an appropriate period for
reflection
– + + – – + +
Reassurance by the physician that the participant understood
the information + + – – – + +
Providing a copy of the IC forms and explanations about the
study – – + – + – +
Date and place of the "Informed Consent" – – – – – – +
The study is conducted by experts according to ethics
guidelines – – – – – + –
The principal investigator obtains the consent or assigns a
delegate + + + – – – +
Consent renewal when needed – + + + – – –
Total items 44 21 35 28 17 20 15 26
RESULTS
The similarities and differences observed in the seven guidelines
with regard to the five selected components of informed consent
were highlighted in Table 2. Each guideline contains at least 15
or more items of the 44 viewed items to be disclosed to potential
participants in research studies when their IC is obtained. The
CIOMS guidelines have the highest number of items relating
to IC 35, followed by ICH-GCP 28 and then the Implementing
Regulations 26 elements. The DoH, CFR, CHRB, and HRA come
at the end of the list with only 21, 20, 17, and 15 elements of IC,
respectively.
Disclosure to participants
All seven guidelines concur on information disclosure. The
essential content to inform the participants includes the fact that
this is a scientific study (research), the aims of the research, the risks
and benefits, trial-related injury compensations and/or treatment,
freedom to withdraw from the research without victimization, and
confidentiality of participant identification information.
An invitation to participate in research is mentioned in CIOMS
(Guideline 9), CHRB (Article 13), the CFR (Sec. 50.25), and
the Implementing Regulations (Article 11.2) but not in the
DoH, ICH-GCP, or HRA. Only CIOMS and the Implementing
Regulations (Article 11.2) mention the title of the research study.
While the study methods, e.g., randomization, are mentioned in
CIOMS (Guideline 9) and ICH-GCP (Paragraph 4.8.10), they
are not included in the DoH, the CHRB, the CFR, the HRA,
or the Implementing Regulations. The duties and functions
of the participants connected to the study, including follow-up
appointments, are referred to in the DoH (Paragraph 26), CIOMS
(Guideline 9), ICH-GCP (Paragraph 4.8.10), and the Implementing
Regulations (Article 11.2) but not in the CHRB, the CFR, or the
HRA.
Except for the Implementing Regulations, all ethical guidelines
mention potential discomfort or burdens. Alternative interventions
beyond the research and their potential risks and benefits are
referred to in CIOMS (Guidelines 4 and 9) and ICH-GCP
(Paragraph 4.8.10), the CFR (Sec. 50.25), and the Implementing
Regulations (Article 11.2) but not in the DoH, the CHRB, or
HRA. Researchers’ institutional affiliations and potential conflicts
of interest are mentioned only in the DoH (Paragraph 26) and
CIOMS (Guideline 9). CIOMS (Guidelines 13 and 5) and ICH-
GCP (Paragraph 4.8.10) mention participants' payment (if any)
and the use of different interventions. The chance to receive a
placebo intervention or no intervention is not included in any
of the seven guidelines. There are two IC elements (the blinding
of the participant or the physician, and the requirement of
an ethics committee approval) that are mentioned only in the
CIOMS guidelines (Guideline 6 and Guideline 23). Only the
ICH-GCP guidelines (Paragraph 4.8.10) mentions the existence of
another study group that may receive a seemingly more appealing
intervention if the research allocated a participant to the control
group. The CFR guidelines (Sec. 50.25) is the only stating that a
new treatment can cause unwanted effects that one cannot reliably
predict and that these can harm the participant.
The source of funding for the study is mentioned in the DoH
(Paragraph 26), the CIOMS guidelines (Guidelines 9 and 25),
and the CHRB (Article 13), but not in ICH-GCP, the CFR, the
HRA, or the Implementing Regulations. While the name of the
institution approving the research (that is, the IRB) is only included
in the Implementing Regulations (Article 11.2), the emphasis on
the contact person(s) can be found in the ICH-GCP (Paragraph

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(Paragraph 4.8.7), the HRA (Article 16), and the Implementing
Regulations (Article 12.1), it is not mentioned by the DoH, the
CHRB, or the CFR. The requirement that consent should only
be sought after the physician has ensured that the participant
understands the information is mentioned by the DoH (Paragraph
26), CIOMS (Guideline 9), HRA (Article 7), and the Implementing
Regulations (Article 12.1). This is not mentioned in the ICH-GCP,
the CHRB, or the CFR.
Providing a copy of the IC form and explaining the study to
subjects are required by the ICH-GCP (Paragraph 4.8.11), the CFR
(Sec. 50.27), and the Implementing Regulations (Article 13.4), but
they are not mentioned in the remaining four guidelines. The date
and place of the IC are specified in the Implementing Regulations
(Article 11.2). Conducting a study by experts according to ethical
guidelines is mentioned only in the HRA (Article 10). Obtaining
“informed consent” shall be done by the principal investigator
or their delegated assistant, as specified in the DoH (Article 26),
CIOMS (Guideline 9), ICH-GCP (Paragraphs 4.1.5 and 4.8.5), and
the Implementing Regulations (Article 13.3). However, this is not
included in the CHRB, the CFR, or the HRA. Consent renewal was
only mentioned in CIOMS (Guideline 9), ICH-GCP (Paragraph
4.8.2), and the CHRB guidelines (Article 24), (see Additional file
1).
DISCUSSION
The analysis of various IC standards shows significant variation
in most parameters regarding the five facets under consideration:
disclosure, comprehension, voluntariness, competence, and
consent. However, it is also evident that there are several similarities
between the KSA and international standards.
Areas of consensus
The disclosure facet highlights several similarities between the
KSA and the international standards. Disclosure is the first
factor to consider while analyzing IC standards. This element has
the highest number of parameters, which allows researchers to
obtain full disclosure [15]. The Implementing Regulations and
the international standards agree on the basic information about
participants. Therefore, researchers using either standard have
the mandate to maintain high confidentiality levels for entrusted
information and should also develop strategies to respect the
confidentiality promise given in ICs [16]. Although not in all
international standards, the analysis noted important areas of
consensus in the invitation to participate, the presentation of the
research title (only in the Implementing Regulations and CIOMS),
and the institution approving the research. These parameters are
essential in research. For instance, Nesom et al. explained that
most standards require approval by Institutional Review Boards.
The researchers also noted that IRBs use standardized variables
and therefore there are no major variations across institutions [17].
The regulations ensure that the research adheres to institutional
guidelines and does not violate the affiliate’s domestic or
international standards.
The analysis also highlights several similarities between the
international and KSA ethical laws on the comprehension
component. International standards such as CIOMS, ICH-GCP,
and the DoH acknowledge the need for ICD simplification,
which is also evident in the Implementing Regulations. The
Implementing Regulations and most international standards also
allow the participants to seek clarification and question the IC
for more clarity. The use of clear and non-technical language in
4.8.10), the CFR (Sec. 50.25), and the Implementing Regulations
(Article 11.2).
The provision on informing the participants of findings that might
affect their willingness to participate in the research is mentioned
in the CIOMS guidelines (Guideline 9), the ICH-GCP (Paragraph
4.8.10), the CHRB (Article 24), the CFR (Sec. 50.25), and the
Implementing Regulations (Article 11.2), but not in the DoH
or the HRA. Receiving study results is mentioned in the DoH
(Paragraph 26), CIOMS (Guideline 9), CHRB (Article 13), CFR
(Sec. 50.25), and HRA (Art. 8), but not in the ICH-GCP and in the
Implementing Regulations.
The possible termination of participation without the subject's
consent due to foreseeable reasons and/or circumstances is
only included in CIOMS guidelines (Guideline 4), ICH-GCP
(Paragraph 4.8.10), and the CFR (Sec. 50.25). Two of the seven
guidelines (ICH-GCP, Paragraph 4.8.10, and CFR, Sec. 50.25)
require disclosure of the approximate number of participants. All
six guidelines, except the DoH, mention the expected research
duration. The DoH (Paragraph 32), the CIOMS (Guideline 11),
the CHRB (Article 13), and the HRA (Art. 32) discuss the need
for further details in the case of genetic research and the possible
future use of biological materials collected during the research (see
Additional file 1).
Comprehension
The DoH (Paragraph 26), CIOMS (Guideline 9), the ICH-GCP
(Paragraph 4.8.6), and the Implementing Regulations (Article 12.1)
agree that the ICD should be simplified as much as possible, and
the information should be designed in an easily understandable
language for all subjects. However, this requirement is absent
from the CHRB, the CFR, and the HRA. The verification of
information comprehension through questions and clarifications
is only stated in the DoH (Paragraph 26), CIOMS (Guideline 9),
and the Implementing Regulations (Article 12.1), (see Additional
file 1).
Voluntariness
With the only exception of the HRA, all other guidelines refer
explicitly to the need to indicate voluntariness as part of IC,
which is understood as a voluntary participation or the right of
the participant to refuse participation. Taking preventive measures
for dependent relationships and consent under duress are only
listed in DoH (Paragraph 27), CIOMS (Guideline 9), ICH-GCP
(Paragraph 1.61), and the Implementing Regulations (Article 12.1),
(see Additional file 1).
Competence
All guidelines, with the exception of the CFR, require the physician
to consult a legally authorized person when participants are unable
to give informed consent (incompetent or vulnerable subjects and
minors), (see Additional file 1).
Consent (Formal requirements of informed consent)
The seven guidelines recommend that the documentation of IC be
made in written form. While the signature of the human subject
is mentioned by CIOMS guidelines (Guideline 9), the ICH-GCP
(Paragraph 4.8.11), the CFR (Sec. 50.27), and the Implementing
Regulations (Article 11.2), it is not mentioned by the DoH, the
CHRB, and the HRA. Some ICs allow a reflection period for the
subjects before they sign the consent. Although this is included
in the CIOMS guidelines (Guidelines 9 and 25), the ICH-GCP

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the source of funding and termination of participation by the
researchers. The KSA standards do not include these components
in their IC. Some of the highlighted factors can significantly affect
the outcomes of a researcher. For instance, a conflict of interest
from research funders (such as funding by drug companies or the
government), might affect the research direction [23].
Furthermore, the study method enables participants to understand
the course of the study and decide whether to participate or not. It is
important to inform them before the start of a randomized placebo-
controlled trial that they may receive a placebo. Participants have
the right to receive all information about the study that is relevant
to their decision to participate or not. This specifically includes
knowing about the possibility of receiving a placebo instead of
an active treatment. Potential participants may feel that a placebo
cannot help them and prefer to choose another therapy that is more
promising in their eyes, outside of the trial. Therefore, it should be
mandatory in ethics guidelines to inform about the possible receipt
of a placebo. There is also a debate among scientists as to whether
exceptions to the strict requirement of individual patient consent
are permissible or even necessary in certain circumstances in order
not to falsify the study results [24,25].
Regarding the information about the expertise of researchers, the
KSA ethical standards do not state that the IC form should mention
that circumstance, in contrast with the HRA, which requires the IC
to include such information. Nor do the KSA guidelines specify
the need for consent renewal, as it is stipulated in the CIOMS
standards. It must be mentioned that re-consenting is common in
many studies and requires participants to sign informed consent
forms in order to participate in the study again. However, it is
important to note that re-consent is different from reaffirming
a willingness to continue in a study after reconsidering various
factors and the research progress [26].
Best methodological practice recommendation
The analysis reveals numerous similarities between the KSA and
international standards. Not all international standards have
similar components in their ICs. All the proposed standards
are effective in guiding researchers about the information to be
provided to participants. Most of these recommendations are based
on studies on areas that might breach ethics in research such as a
lack of detailed information about the risks resulting from study
participation [27]. Another essential factor is the participants’
understanding of IC and related ethics. This suggests that it is
vital for principal investigators and other researchers to ensure that
participants understand the research process and risks associated
with various research procedures. In addition, studies on IC and
medical research ethics have revealed variations in institutional
guidelines, but with similar weaknesses [28]. The differences and
weaknesses of institutional ethics mechanisms suggest a need to
regulate institutional ethical review boards. The recommendation
is also essential for the KSA standards.
Two very concrete items are particularly important for the protection
of participants' rights: The first is the name of a contact person
for further information. In times of service, which is provided by
an artificial intelligence system, it is a special protection for study
participants if they are given a contact person for further questions
about the study. The second item is the handing out of a copy of
the consent form to the study participant. Even though there are
illiterate people who cannot read the provided information, the
IC in written format should always be provided to participants
the IC form is essential to facilitate participants' understanding,
especially when participants have low educational backgrounds.
For such populations, researchers need to develop and use
better communication strategies to improve their understanding
of the clinical trial [18]. Seeking clarification depends on the
participant's ability to understand the consent content. Lack of
questioning or clarification from the participants often indicates
a lack of understanding. Lack of understanding and inability to
seek clarity may pose a great risk, especially for high-risk studies.
Current studies have shown that only 50% of participants have a
good understanding of the planned research, including blinding,
voluntary participation, and freedom to withdraw from a study
[19]. Therefore, it is vital to ensure that the IC form is written in a
language understandable by a layperson.
Voluntariness and competence are other essential components
of IC. In this regard, several similarities can be found between
the international and KSA ethical standards. Indeed, all the
international standards and the Implementing Regulations express
the need to promote voluntariness. The concept of voluntariness
also includes the freedom to refuse to participate in research. Also,
the KSA research ethics and several international standards concur
on the dependent relationship of consenting under duress. The
concept of voluntariness aligns with the principle of autonomy in
research. All researchers must ensure participant autonomy [20]. In
some instances, researchers may require the input of incompetent
participants, minors, and particularly vulnerable subjects. In such
instances, the international standards and KSA ethical standards
emphasize the need for the consent of the authorized legal
representatives. The researchers should always be in contact with
participants’ representatives. The concept of legal representatives
extends to vulnerable populations and illiterate participants [21].
In bioethics research where participants are pregnant women,
researchers may need to seek approval from the fathers, who are
considered legally competent parties in this case [22].
All the standards recommend that consent be in written
format. In addition, the Implementing Regulations, and several
international standards (CIOMS, ICH-GCP, and the Code of
Federal Regulations) allow participants to confirm that they have
understood the consent and are ready to participate in research.
Both sets of standards (KSA and International) allow a reflection
period and require the provision of a copy of the IC to participants.
Bioethics standards consider written formats to be the most basic
principle of IC [19]. This explains why most ethical standards
concur with providing this format to all participants.
Areas of disagreement
The wide variability in the elements required by the guidelines is
shown by two figures: Only 7 of the 44 elements considered are
found in all the guidelines, and 19 of the 44 elements considered
are found in three or less of the seven guidelines.
The two sets of ethical guidelines have several variations in many
components of the IC. On disclosure, two international standards,
CIOMS and ICH-GCP highlight the methods used in research,
which are absent in the Implementing Regulations. Also, all the
international laws mention the burden and discomfort of the
research study, which is lacking in the Implementing Regulations.
The Implementing Regulations do not mention conflicts of interest
in a study, in contrast to the DoH and CIOMS ICs. In addition,
international standards, such as CIOMS, require approval by the
ethics committee, while several international standards include

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Al-Madaney MM, et al.
J Clin Res Bioeth, Vol.14 Iss.6 No:1000475
so that they can discuss it with others later or inform the primary
care physician. The KSA guidelines included both items as well as
CIOMS and CFR.
Areas of future research
The analysis of the IC concepts exposed several gaps that might need
detailed research. One of the factors of interest was the variation
of standards in different regions. For instance, the highlighted
differences between ethics in KSA and federal standards in the
USA. Researchers have shown that cultures could influence the
differences in the guidelines [29]. Due to this, the researcher needs
to assess the extent to which culture affects the formulation of
the standards. The second factor needing detailed investigation
is variation in understanding the IC guidelines. Researchers
should focus on assessing whether participants might have varying
comprehension abilities for different concepts, as highlighted in
different standards. The research should also highlight which
standards the participants comprehend best.
Strengths and limitations of the study
The strength of this paper lies in its comprehensive analysis and
comparison of the informed consent guidelines both internationally
and in Saudi Arabia. This paper provides a thorough examination
of the quality of informed consent in Saudi Arabia and highlights
the need for improvements. The study was unable to address
several factors related to the topic. These include the applicability
of the international standards in Saudi Arabia, factors influencing
preferential use of the international standards in various regions,
and the variation in participants’ (doctors' and patients') perceptions
of the informed consent standards. Additionally, the study did not
completely analyze the whole content of the bioethics standards,
which is a complex and broad topic requiring the input of multiple
researchers. Future studies should also focus on these limitations.
Challenges
During the process of data extraction, we encountered several
challenges. We faced a challenge of inconsistency in the terminology
used by different guidelines, which caused disagreements between
researchers about certain elements of informed consent. To resolve
these disagreements, we held a meeting to discuss the issues and
analyze the content thoroughly to make sure the data was accurate
and consistent. Another challenge we encountered in our data
extraction process was subjective judgment, as researchers may
interpret the importance of certain provisions differently. To
address this challenge, we provided clear criteria that reflect the
foundational principles of informed consent, which were used for
critical analysis. A single researcher handled data collection and
initial analysis, which raised the possibility of bias and subjectivity
on their part. Then preliminary data were presented to the full
research team for peer review and reflection on potential researcher
bias. Furthermore, a second researcher reviewed the analysis outputs
to validate the findings. Finally, a full research team critically
examines these biases and ensures they do not influence the
data collection and analysis process. The authors addressed these
challenges explicitly within the paper through the transparency and
reliability of their methodology, to provide a clearer understanding
of the above-mentioned study's limitations and strengths.
CONCLUSION
Ethical standards are important in medical research, as they aim to
protect participants and minimize negative outcomes. This analysis
has compared six different international, regional, and national
standards with the informed consent guidelines in Saudi Arabia.
The analysis has focused on the basic information requirements
and variations in the five components of informed consent. From
this analysis, it can be concluded that some essential concepts
present in other standards are missing in the KSA regulations.
Moreover, the research has noted that there are significant
differences among the six standards, which may reflect cultural or
contextual variations rather than deficiencies. Furthermore, these
variations in regulations may also reflect the evolution of ethical
considerations and the incorporation of new principles over time.
It is important to consider that the participants' comprehension
ability may vary depending on the variations in these standards,
which could potentially affect their informed consent decisions.
Therefore, it is essential for researchers and healthcare professionals
to take these variations into account and make an effort to ensure
that all participants have a clear understanding of the study and
receive accurate and comprehensive information before making
informed consent decisions, regardless of the standard used to
obtain informed consent.
The study's main contributions lie in providing policymakers
and healthcare providers with valuable insights into the ethical
considerations surrounding informed consent in Saudi Arabia,
helping them develop more effective guidelines that align with
the country's cultural and legal context. Overall, upholding
ethical standards in research studies in Saudi Arabia benefits not
only the participants but also researchers, who can add valuable
insights within the research ethics field. This can contribute to
the advancement of knowledge and ethical practices in the field
of ethics. Also, contribute to the development of guidelines and
protocols that can be implemented in future medical research
studies.
SUPPLEMENTARY INFORMATION
Additional file 1
Comparison of 44 informed consent elements from different
ethical guidelines
DECLARATIONS
Funding
No funding from any source was given for this study.
Acknowledgements
Not applicable
Ethics approval and consent to participate
Not applicable
Availability of data and materials
The datasets used during the current study are available from the
corresponding author on reasonable request.
Consent for publication
Not applicable
Competing interests
Not applicable
Authors' contribution
MM contributed to the study design, data collection, data
analysis, and interpretation, and drafted the initial manuscript.

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Al-Madaney MM, et al.
J Clin Res Bioeth, Vol.14 Iss.6 No:1000475
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