Case Study "What Makes Clinical Research Ethical? Case Study: Developing a Vaccine for Malaria

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Dr. Obumneke Amadi-Onuoha_Scripts
Case Study "What Makes Clinical Research Ethical?
Critical Analysis - CRA -
Case Study: Developing a Vaccine for Malaria
The participant’s experience case study I incorporated into this critical analysis is
obtained from the Principles of Research Ethics casebook. The “Developing a Vaccine for
Malaria” (Cash, Capron, Gutnick, Saxena, & Wikler, 2009). This case study examined the
designing of a scientifically valid and valued study, and if the research favorable risk- benefit
ratio is fairly distributed. Ethics in general involves the moral principles that guides the methods
of conducting activities or an individual behavior while incorporating into medicine and health, it
is referred to as bioethics, otherwise called clinical research. The purpose of clinical research is
to obtain knowledge and in –depth understanding of human health; to realize this purpose, the
participants involved are at risk of harm or exploitation by the investigator’s using the services.
Therefore, to prevent these case scenarios from participants, the ethical requirements in clinical
research that support minimizing possible exploitation and ensure that the rights and welfare of
these participants are established by certain codes and guidelines referred as Nuremberg Code
(1949), Declaration of Helsinki (2008), the Belmont Report. These are focused on the ethical
concepts of 1) respect to persons, 2) beneficence and 3) justice, (Emanuel, Wendler, & Grady,
2000, p.2701-2701). Informed concept is being adopted into all research bodies; IRBs, bioethics,
and investigators in human subject research as a guideline to obtain voluntary consents from
participants to participate in a research. Informed consent is given for a participant’s protection
and involvement; however, other concerns arise toward ethically evaluating clinical studies
(Emanuel, Wendler, & Grady, 2000, p. 2071). Emanuel, Wendler, & Grady (2000) listed seven
principals for research ethics: social or scientific value, scientific validity, favorable risk-benefits
ratio, fair subject selection, independent review, and respect for potential and enrolled subjects
(p. 2701-2703). The seven ethical requirements were generated to clearly explain the common
ethical standard obligations specific to clinical research and are concentrated on intellectual
honesty and responsibility as a systematic framework to ethically evaluate clinical studies.
Though universally implemented, this requires cultural and economic adaption based on each
applying country (Emanuel, Wendler, & Grady, 2000, p. 2072). The three requirements that I
propose important to evaluate the ethics of clinical research studies are: 1) social or scientific
value, 2) scientific validity, and 3) favorable risk-benefits ratio. My rationale for choice is based

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on the shared qualities presented by the informed consent requirement that have conceptual and
theoretical associations with the, ‘fair subject selection, independent review, and respect for
potential and enrolled subjects with reverence to ethical rules that include, respect for subject
autonomy and welfare, scientific knowledge, ethical and legal knowledge, and Belmont’s report
- nonmaleficence, beneficence, and no exploitation’ (Emanuel, Wendler, & Grady, 2000,
p.2073).
Social or Scientific Value
Clinical research must have the capacities of proven assessment of the observation it
seeks, either diagnostic or therapeutic that may inform solution or advancements in human
health. Investigator’s observations should be able to generalize results and practicably
implemented regardless if the effects are no valuable. Social value in clinical research gives the
society open access to increased knowledge of the health problem interventions through
disseminating study results through publications. According to Moher, et al. (2016), it is the
responsibilities of researchers to ensure a systematically planned research that is of value and
grantees reliable evidence by reducing waste and increasing value in biomedical research and
also, preventing participants and researchers from being disadvantaged from making informed
decisions about healthcare. In the case study, there was no clear intervention to measure the
efficacy of vaccine; this aspect deters the entire value of ethical research requirement (Cash,
Capron, Gutnick, Saxena, & Wikler, 2009, p.61). It can be argued that the study should to be
conducted in agreement with GCP. In addition, putting the ethical scientific value of designing a
malaria vaccine for children instead of adults in consideration, though informed consent may be
obtained from children’s parents, a question may arise demanding the rationale for justifying a
pediatric age group versus the adult population as enrollment criteria for the research project. To
address this question, it can argued that the choice of participants would promote the value to
encourage and facilitate on timely product generation of pediatric vaccine among many different
nations, and help design different vaccine formulation from different age group. Social or
scientific value are integral ethical requirement because it promotes the responsible use of
resources, prevents exploitation and creates good comparison of different clinical studies for
better choice of treatment and feasible implementation (Emanuel, Wendler, & Grady, 2000,
p.2703).
Scientific Validity
A methodologically rigorous study is required to confer clinical research as being ethical,
otherwise participant may be exposed to risk. According to Taichma, et.al.(2017), data sharing
is considered an important step towards best practice in clinical trials because participants have
put themselves at risk from de-identified data; however, if made a norm, this may help to reveal
real or perceived risks to trial participants including researchers and help them make better
decision towards the study participation and planning. However, being ethical, entail strong and
organized protocol that is valid, practically conventional, clear scientific objectives, able to test
hypothesis, can produce credible analytical ideas’ using agreeable principles. However, from the
case study analyzed, the issues of ethical assessment of the participants(children) after they

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receive the vaccine, without further interventions is questionable, the study design may not
present appropriateness to demonstrate the efficacy of the vaccine and as well put patients at risk
(Cash, Capron, Gutnick, Saxena, & Wikler, Eds.,2009, p.61), however, in this case scenario,
Limit is 2-3 pages for this assignment; graded portion will stop here.
where the investigators are from outside the country, a question may arise as how would
the country’s local regulatory board handle such problem?- i.e. they lack the context-specific
details relevant to the project, it can be suggested that a risk- benefit assessment be taken
seriously with focus on minimal risk, and also establish an independent data monitoring panel in
support of trail management project progress, this also, can minimize any form of participants’
exploitation e.g. in the case of Grimes v. Kennedy Krieger Institute court case that debated over
the core ethical issues of research protocol and guidelines with vulnerable children, the court
ruled against and was not in favor of allowing research that put children at risk of harm and also,
that do not give a promising therapeutic future benefit to them(National Academy of Sciences,
2019, p.44). Furthermore, it can be argued that investigators should understand that it is
important that a good study design and question that can answer if new intervention is better than
the standard one to resolve the uncertainty within investigators understanding of treatment
options, understanding methodological recommendations is critical to ensure the quality and
generalizability of research studies (Evans, et al. 2015, p.161). The rational of scientific validity
in clinical research, connects to its theory to prevent exploitation of resources, participants and
promotes knowledge and advances benefits to heath improvement (Emanuel, Wendler, & Grady,
2000, p. 2704).
Favorable Risk-Benefits Ratio
In clinical research minimal risk of harm to the participants are considered ethical,
therefore, investigator must make certain that the benefit of participates involvement precisely
outweighs the amount of risk. Investigators should take into great account the consistency with
the aims of the study and the practice standards, also, Wieschowski, Chin, Federico, Sievers,
Immelmann, & Strech (2018) in their study explained that favorable risk–benefit judgments are
necessary prior to takeoff of clinical trials as a measure to balance risk for participants. The
investigators in this case study are aware of the high risk participants are exposed in the
intervention, and their measure is the only important measure of vaccine success for the study,
e.g. according to National Research Council (2004), in general medicine treatment
(pharmacotherapy), children have different features compared to adults, thereby justifying ethical
concerns of the inclusion of children into clinical research, because e.g. vaccines must be
studied in children to help their safe and effective use( p.66), however, if the question arises as
‘how justifiable is the ethical favorable risk-benefits ratio towards participants and investigators
participating in the study’? It can be answered that, it is important that the investigators discern
the reason for clinical ethical requirement to enhance the potential benefits of participant and the
society, and preventing exploitations at all categories (Emanuel, Wendler, & Grady, 2000, p.
2076).

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Overall, while the ethical principles of the social or scientific value, 2) scientific validity,
and 3) favorable risk-benefits ratio, encompasses the ethical guides of the Belmont’s report - no
maleficence, beneficence, and no exploitation, towards good clinical research practice in
compliance to regulations and protection to the human subject, the ethical principles surrounding
informed concepts should not be overlooked, e.g. National Research Council (2004), stated that
permission and assent are closely linked to foundations protocol of ethical research involving
children(p.147). Also, practical considerations are necessary to ensure adherence to ethical
clinical research requirements.
Case Study Summary
In the case study “Developing a vaccine for malaria” (Cash, Capron, Gutnick, Saxena, &
Wikler, 2009), a north American university group of investigators planned to test a multistage,
DNA malaria vaccine in sub-Saharan Africa were malaria is endemic and countries are interested
in participating in a vaccine trial effort. The investigators developed study design of the protocol
used to assess the efficacy of the vaccine to reduce severity of mortality caused by malaria in
pediatrics. Trained community health workers visited homes and obtain demographic and health
data of the indigenes and store in a centralized data storage tool that was updated on regular
basis. The villages are in remote areas, thereby limiting health post to serve all the population,
including shortage of health practitioners, and resources. Because of this problem, the
investigators organized study vaccination teams that would go into homes, educate and obtain
consent from participants caretakers, the investigators then administer vaccine to participants, the
team leaves without implementing intervention in case of adverse effects. Also, there was not
defined measurement for the efficacy of the vaccine apart from death. The Children participants
presented in this case study “Developing a vaccine for malaria” (Cash, Capron, Gutnick, Saxena,
& Wikler, 2009) were most likely exposed to poor and at risk interventions, and lack of proper
study evaluation and planning, the participants mostly children are subjected to ethical issues of
decision making (informed consent) because of their age, and other aspects of ethical guidelines
that include social or scientific value, scientific validity, and favorable risk-benefits ratio.
Please, find the case study in reference section to read further.

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Reference
Cash, R., Capron, A. M., Gutnick, R., Saxena, A., & Wikler, D. (Eds.). (2009). Case 10.
Developing a vaccine for malaria. Casebook on ethical issues in international health
research. World Health Organization. Retrieved
fromhttps://apps.who.int/iris/bitstream/handle/10665/44118/9789241547727_eng.pdf;jsessi
onid=CF35D7B15FECE9648FDA503FBF1C3F5D?sequence=4
Emanuel, E. J., Wendler, D., & Grady, C. (2000). What makes clinical research ethical? Jama,
283(20), 2701-2711.
Evans, S. C., Roberts, M. C., Keeley, J. W., Blossom, J. B., Amaro, C. M., Garcia, A. M., &
Reed, G. M. (2015). Vignette methodologies for studying clinicians’ decision-making:
validity, utility, and application in ICD-11 field studies. International Journal of Clinical
and Health Psychology, 15(2), 160-170.
Moher, D., Glasziou, P., Chalmers, I., Nasser, M., Bossuyt, P. M., Korevaar, D. A., &
Boutron, I. (2016). Increasing value and reducing waste in biomedical research: who's
istening?. The Lancet, 387(10027), 1573-1586.
National Research Council. (2004). The Ethical Conduct of Clinical Research Involving
Children. Washington, DC: The National Academies Press, 448, 18.
National Academy of Sciences (2019). Ethical Considerations for Research on Housing-Related
Health Hazards Involving Children (2005): Chapter: 3 Grimes v. Kennedy Krieger
Institute: Revisiting the Ethical Issues. Retrieved from
https://www.nap.edu/read/11450/chapter/5
Taichman, D. B., Sahni, P., Pinborg, A., Peiperl, L., Laine, C., James, A., & Frizelle, F. A.
(2017). Data sharing statements for clinical trials: a requirement of the International
Committee of Medical Journal Editors. Annals of internal medicine, 167(1), 63-65.
Wieschowski, S., Chin, W. W. L., Federico, C., Sievers, S., Kimmelman, J., & Strech, D. (2018).
Preclinical efficacy studies in investigator brochures: Do they enable risk–benefit
assessment?. PLoS biology, 16(4), e2004879.