Efficacy of Thalidomide in Preventing Delayed Nausea and Vomiting

This article analyzes the efficacy of thalidomide in preventing delayed nausea and vomiting induced by highly emetogenic chemotherapy. It discusses the study design, participant allocation, blinding, follow-up, and results. The study concludes that thalidomide, when combined with palonosetron and dexamethasone, offers positive clinical outcomes with mild side effects. The findings can be applied to chemotherapy-naive patients.

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Article analysis
Students Name
University
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Zhang, Lingyun, Xiujuan Qu, Yuee Teng, Jing Shi, Ping Yu, Tao Sun Jingyan Wang, Zhitu Zhu,
et al. 2017. "Efficacy of Thalidomide in Preventing Delayed Nausea and Vomiting Induced by
Highly Emetogenic Chemotherapy: A Randomized, Multicenter, Double-Blind, Placebo-
Controlled Phase III Trial (CLOG1302 study)." Journal of Clinical Oncology 35 (31): 3558-
3565.
1. Did the study ask a clearly focused question?
(Zhang, et al. 2017)Yes, the study question is clear and can be easily understood by the reader.
This both from the topic of the article and the summary of the purpose which is in the abstract.
The study was based on patients who had received highly emetogenic chemotherapy (HEC).
Thus the intervention given for this study is thalidomide which was uses in highly emetogenic
chemotherapy (HEC) to determine whether it reduced delayed nausea and vomiting. Randomized
control trials are used to measure the effectiveness of a medical intervention that is done on the
patient by having two groups, the general group which can sometimes be the placebo group and
the control group which is the one that is used to measure the effectiveness of the intervention1.
These type of studies are the best since they allow the researcher to compare two groups which
lead the researcher to conclude the effectiveness of the new clinical method or drug being tested.
In this case, the focus is determining whether thalidomide can be effectively used on reducing
nausea.
2. Was this a randomized controlled trial (RCT) and was it appropriately so?
This study is a placebo randomized control trial since it had two patient groups. Double-Blind,
Placebo-Controlled Phase III Trials are used for the trial of patients in different clinical settings
1 Hariton, Eduardo, and Joseph J. Locascio. 2018. "Randomised controlled trials—the gold standard for effectiveness research." BJOG,
p. 3.

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to determine if certain drugs are applicable to them or not. This means that two groups are used
as a placebo group and the control group. The role of the former is to receive drugs that have no
real effect so that the differences can be noted and analyzed in the control group2. Randomized
trials are the best since they are used to test the clinical effectiveness of different types of drugs
and thus the reason why this research was fit for the study. By being a randomized placebo trial,
the researchers were able to compare data from two groups of patients, one which was a placebo
and the other one which was a control group that was administered with thalidomide to
determine the effects that it has on the patient group. Through comparing the results from the
two groups the researcher is able to determine the effectiveness of the clinical intervention being
tasted3. Thus a randomized control trial is the best for this study since the participants are
randomly placed in the groups increasing the generalizability of the findings. In such case,
skewing and manipulation of the results are limited thus ensuring that the study yields the best
outcomes of the study.
3. Were participants appropriately allocated to intervention and control groups?
The patients were randomly assigned to the groups based on stratification using a computer-
generated sequence that ensured that both groups had an equal number of patients for the study.
This ensured true randomization in the ratio of 1:1. To balance the randomization easily, four
blocks were established and patients distributed across the blocks to increase monitoring and
assessment. The patient data was recorded from day one to five with short-term adverse events
being evaluated within day 1-5 while serious events were recorded and evaluated for a period of
up to 21 days. For this study two outcomes were considered, the primary outcome was a
complete response of the patient to vomiting without the use of any drugs and no emetic episodes
2 Chiodo, Gary T, Susan W Tolle, and Leslie Bevan. 2018. "Placebo-controlled trials." Western Journal of Medicine, p. 272
3 Gupta, Usha, and Menka Verma. 2013. "Placebo in clinical trials." Perspectives in Clinical Research, p. 643

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or rescue medication. The secondary measure for the study was a complete response to vomiting
during the acute situation described as happening between 0-24 hours and overall 0-120 hour’s
response with a lack of nausea within the three days and anorexia scores. Thus when
documenting the results, lack of nausea was documented as zero using a Likert scale of four
points. This scale is effective in ensuring that the patient responses are rated using the four levels
that define the characteristics which can be used to differentiate between the placebo and the
control group.
4. Were participants, staff and study personnel ‘blind’ to participants’ study group?
The investigators, assessors, patients, and sponsors were all blinded in the study and did not
know which patients received the treatment thus ensuring that the group is protected. The
intention is to reduce performance bias from the investigators and the patients who may
manipulate the results in their own way. Since the aim of the study is to find the optimal
treatment option for the situation under investigation, the validity of the results is important in
arriving at the right conclusion that meets the needs of the study. Reducing bias in a study
increases the validity and generalizability of the findings which ensures that the research arrives
at a valid conclusion4. Sometimes, patients may detect the effect of a certain treatment even if
they are blinded thus the reason why this study used a double-blind approach. Here both
participants and personnel are also blinded to increase the effectiveness of the treatment method.
5. Were all of the participants who entered the trial accounted for at its conclusion?
All the participants in the study were accounted for including those who dropped off. The
patients who dropped off were excluded from the final analysis of the study thus ensuring that
only those who participated in the study to the end were included. The participants in the two
4 Heger, Pascal Probst Kathrin Grummich Patrick, Steffen Zaschke, Phillip Knebel, Alexis Ulrich, Markus W. Büchler, and Markus K.
Dienercorresponding author. 2016. "Blinding in randomized controlled trials in general and abdominal surgery: protocol for a systematic review
and empirical study

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groups were assessed differently to ensure the changes in the two groups were captured to
understand the differences between them. All the participants in the group were analyzed in their
groups to assess the effect of the treatment on the control group. The placebo group was assessed
and the differences between the group and the control group were analyzed to determine the
effect of thalidomide in highly emetogenic chemotherapy patients.
6. Were the participants in all groups followed up and data collected in the same way?
All participants in the two groups were followed up until the end of the study. In the beginning,
patient daily records of vomiting episodes and the degree of nausea were recorded daily by
contacting the patients for one to five days by analyzing the effects of chemotherapy. Any
adverse effects of the patient were recorded within the five days which formed the basis of
analysis. Through a four-point Likert scale the patient was analyzed based on the characteristics
that they portrayed. The measure for the patients was an emetic episode defined as one
occurrence of vomiting that occurred in close succession. The primary focus of the study was a
complete response to vomiting with no emetic episodes and no use of rescue medication which
was delayed and lack of nausea was defined as a score of zero using a 4-point Likert scale. All
patients were followed up during the study to document the outcomes of the study and the
differences between the two groups. The success of randomized control trials is based on
assessing the patients in the two groups so that the differences between them can be assessed and
presented. Patients have to be followed up in their respective groups so that the developments in
the control group and what has been initially documented in the placebo group to determine the
effect of received thalidomide in highly emetogenic chemotherapy.
7. Did the study have enough participants to minimize the play of chance?

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The study had enough participants based on the number of patients that were recruited and met
the criteria of the study. The ratio of the participants in randomized trials is supposed to be the
same since participants are randomly assigned to either of the groups. However, the power of
calculation in this study was not used since the patients that were targeted were captured from
the whole group by establishing exclusion and inclusion criteria to capture the respondents that
are valid for the study5. In this case, the focus was on all patients that met the criteria and qualify
to be included in the study. This means that stratified sampling was only used to assign the
patients to the specific groups that fall under the placebo and the control group. From the study,
the prospective subjects are the one that meets the criteria of the study and qualify to be used
since they will yield the expected results6 (Garg 2016, p. 643). However, this has been
challenged since the recruitment of the participants is purposive by including only the
participants that meet specific criteria. In this case, the eligibility to participate in the study was
18-70 years, with a malignant disease, and were chemotherapy naive and also scheduled to
receive highly emetogenic chemotherapy. This means that the study was based on a specific set
of participants which is different from the rest of the studies that draw a sample from a whole
population. This means that may be a possibility for recruitment bias since the researcher may
have challenges recruiting the participants for the study.
8. How the results presented and what are is the main result?
From the results, 317 patients in the THD group and 321 in the control group delayed and had an
overall complete response rate to vomiting which was higher with the THD group being 76.9%
as compared to 61.7% (P, .001) and 66.1% versus 53.3% (P = .001), respectively. The adverse
effects of the drug on the patient were mild which means that the effect of the drug was the best.
5 Noordzij, Marlies, Giovanni Tripepi, Friedo W Dekker, Carmine Zoccali, Michael W Tanck, and Kitty J Jager. 2015. "Sample Size
Calculations:." Nephrology Dialysis Transplantation, p. 1390
6 Garg, Rakesh. 2016. "Methodology for research I." Indian Journal of Anaesthesia, p. 643

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Despite the patients feeling minimal side effects like increased sedation, constipation, dizziness,
and dry mouth, they reported better outcomes results than the placebo group after chemotherapy.
The size of the result is meaningful and allows the researcher to draw conclusions by comparing
the difference between the placebo and the control group results. This shows that the use of
thalidomide has increased positive clinical effects in chemotherapy patients.
9. How precise are these results?
The preciseness of the study was high because it met the required confidence level for the study.
In randomized control trials, the confidence interval for a good study is supposed to be 95% to
show that the reliability of the findings of the can be applicable to the field of study. A
confidence level of 95% is ideal since the sample was big and it means that this interval meets
the needs of the study7. The effectiveness of any study is seen in the confidence level that it
reports which determines the effectiveness of the findings. The validity of the study is also based
on the level of confidence that the study reports since by focusing on the increased level of
confidence then the study becomes more effective in meeting the needs of the study.
10. Were all important outcomes considered so the results can be applied?
Randomized control trials are the benchmark of any research since the efficacy is based on the
ability to report differences in the clinical outcomes. The outcomes of this study were increased
due to the double blinding approach that allowed maximizing of the benefits of the study. Thus
the main outcome for this study was to measure the effects of thalidomide in highly emetogenic
chemotherapy patients who responded well on the use of the drug. However, the study was
limited by the fact that data history of the patients was not documented which means that some
of the outcomes of the study will have been avoided and at the same time the study did not report
7 Stewart, Suzanne B., Phillip Dahm, and Charles D. Scales. 2011. "How to appraise the effectiveness of treatment." Indian Journal Urology, p.
522

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the efficacy of CINV. However, the study concluded that thalidomide offers the best clinical
outcomes since from all the outcomes that were reported, the study reported positive outcomes in
the control group and no outcome in the placebo group. This study thus concluded that the use of
combining thalidomide with palonosetron and DEX can yield the best results in chemotherapy
naïve patients. The side effects of the drug in the control group were increased sedation,
constipation, dizziness and dry mouth which can be said to be mild to tolerate thus the reason
why the drug offers the best outcome for the users. This study can be applied to the general field
of study since it proposes the use of thalidomide with palonosetron and dexamethasone.

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Bibliography
Chiodo, Gary T, Susan W Tolle, and Leslie Bevan. 2018. "Placebo-controlled trials." Western
Journal of Medicine 172 (4): 271-273.
Garg, Rakesh. 2016. "Methodology for research I." Indian Journal of Anaesthesia 60 (9): 640-
645.
Gupta, Usha, and Menka Verma. 2013. "Placebo in clinical trials." Perspectives in Clinical
Research 4 (1): 49-53.
Hariton, Eduardo, and Joseph J. Locascio. 2018. "Randomised controlled trials—the gold
standard for effectiveness research." BJOG 125 (13).
Heger, Pascal Probst Kathrin Grummich Patrick, Steffen Zaschke, Phillip Knebel, Alexis Ulrich,
Markus W. Büchler, and Markus K. Dienercorresponding author. 2016. "Blinding in
randomized controlled trials in general and abdominal surgery: protocol for a systematic
review and empirical study." Systematic Reviews 5 (48).
Noordzij, Marlies, Giovanni Tripepi, Friedo W Dekker, Carmine Zoccali, Michael W Tanck, and
Kitty J Jager. 2015. "Sample Size Calculations:." Nephrology Dialysis Transplantation
25 (5): 1388-1393.
Stewart, Suzanne B., Phillip Dahm, and Charles D. Scales. 2011. "How to appraise the
effectiveness of treatment." Indian Journal Urology 27 (4): 525-531.
Zhang, Lingyun, Xiujuan Qu, Yuee Teng, Jing Shi, Ping Yu, Tao Sun Jingyan Wang, Zhitu Zhu,
et al. 2017. "Efficacy of Thalidomide in Preventing Delayed Nausea and Vomiting
Induced by Highly Emetogenic Chemotherapy: A Randomized, Multicenter, Double-
Blind, Placebo-Controlled Phase III Trial (CLOG1302 study)." Journal of Clinical
Oncology 35 (31): 3558-3565.

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