Clinical trials lead to conventions in oncology

Shiyin Wang

Writing 2

June 14, 2020

 Oncology is the study of cancer, a chronic disease caused by cells out of control.

These cells lose their function but continue to grow they from tumor, which cause

multiple health problems and death. Oncologist aimed to extend the life expediency

and rise the life quality of the patients. They study and develop better treatments for

cancer through series of researches. Unlike other STEM research, oncology research

involve testing with human. It has a strict research sequence to protect the patients

and minimize the risks. This unique type of research has strong impact on the use of

methodology, evidence, and citation of oncology academic articles.

Clinical research is an important step of the oncology research because therapy work

for animal model may not work for human. Therefore, clinical trials are unavoidable

steps to tests the toxicity and effectiveness of the therapy. Generally, one therapy must

go through three clinical trials to get approvement from FDA. For each clinical trial,

must have notable result in the previous clinical trial to go to the next one. If there are

sever side effect or the effectiveness of the treatment is not notable, the research

cannot proceed. Compare to other experiments clinical trials are much difficult to

perform. Phase one and two take one year while phase three clinical trial takes around

five years to go to completion. According to the research, “the median time to develop

a drug was 7.3 years (range, 5.8-15.2 years) and the median cost of development of a

single drug in 2017 US dollars was $648.0 million” 1

The restrictions on clinical trials cause oncology writings to have detailed

methodology. They have the subtitles to improve the clarity of its structure and they

include every aspects of the research. For example, for the research “Phase 1b study
of pembrolizumab (MK-3475; anti-PD-1 monoclonal antibody) in Japanese patients

with advanced melanoma (KEYNOTE-041)”2 the methodology is divided into three

paragraphs, with subtitle “Patient eligibility”, “Study design and evaluation” and

“Statistical analysis” these subtitles are the summary of the content, they divided the

long methodology in to smaller paragraph making the article easier to follow.

Researchers write in such detail with consider of ethic problem. Clinical trials are

testing on human which have much more ethic concern than just laboratory animals.

The purpose of oncology research is to help the patients, but if the researches are not

performed properly, it will lead to the opposite result. Therefore, researchers must

write a detailed research purpose to NCI to show they have efficient methodology that

consider every single aspects of research. For example, in the research “Phase 1b

study of pembrolizumab (MK-3475; anti-PD-1 monoclonal antibody) in Japanese

patients with advanced melanoma (KEYNOTE-041)” it writes “All the patients

provided informed consent, and the study was conducted in accordance with current

Good Clinical Practice standards. This study was registered at ClinicalTrials.gov

as NCT02180061.” 2 This sentence shows researchers are concerned about the health

of the patient who participate in the research.

The clinical trials in the oncology also have huge impact on the way researchers

present their evidence. Oncologists usually includes the processed statistical data in

their analysis and conclusion rather than the row data they collected during the

clinical trial. For example, in the research “Anti-programmed-death-receptor-1

treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a

randomised dose-comparison cohort of a phase 1 trial”3, the authors present their data

with a diagram. Oncology researches require large amount of data to determine the

effectiveness of a treatment. The reason is if the research was performed just on

certain types of people, there is risk that the therapy may induce health problem in the

others. Which contradict to the purpose of improving life quality. Therefore, the

researchers purposely involve large number of patients covering large range of age

and both gender in clinical trail 2 and 3. For example the clinical trial includes 1783

participants for five years to test the effectiveness of the medicine ipilimumab. 4 It

creates a lot of raw data. If the authors include raw data in their articles. It will

overwhelm the structure of the articles and blur the difference between analysis and

data. This would influence the convention of information and confuse other

researchers. To make the article readable oncologists only represent the statistical data

and include the raw data in the supplemental link.

As demonstrated before, the oncology research does not stand on its own. It

usually belongs to series of researches. These researches have their order and purpose.

Phase 1 clinical trial focus on the toxicity and side effects. Phase 2 focus on the best

dose. Phase 3 focus on the comparison with current therapy. The new following

research is based on the previous research For instance, the phase 3 study it says

“study intravenous pembrolizumab 10 mg/kg every 2 or 3 weeks or intravenous

ipilimumab 3 mg/kg every 3 weeks for four doses (ipilimumab only).” 5 This is most

effective dose found in the phase 2 study of Pembrolizumab6

 Therefore, it usually quotes the research result from previous clinical research in

the introduction or the conclusion of the paper. Also, oncology articles are usually

explaining a research and it develop conclusion using the data from this research.

They generally do not have much citations in the methodology and data analysis. This

quotation arrangement works the best with the CSE style citation. This type of citation

is used primarily in sciences and mathematics. It includes superscripts in the article

when addressed to a source, and reference list corresponds to them at the end of

article. This type of citation creates references lists according to the order of its first

appear in the article and reduce the number of foot notes in the articles. This make the

article more consistent.

CSE citation style are useful for the oncology citations because the result from

one clinical trial could contribute to multiple researches. For example, the data from

phase 3 clinical trial of Pembrolizumab have been addressed to 162 different

researches.5 As demonstrated in the second paragraph, the clinical trials are expensive

and take a lot of time. Therefore, some researches do not have physical experiment,

they perform further analysis with the data from previous clinical trials. In this

circumstance CSE citation eliminate the repetitive citations by putting them at the end

of the articles.

The third reason is the intern reports. Clinical trials usually take a long time so

the researchers share the progress of research by periodical reports before the

completion. This process could be done by different members of the research team. T

For instance, in the article of “Pembrolizumab versus ipilimumab in advanced

melanoma.”7 The phase 3 clinical trial just have the data of response rate and side

effects. This experiment is not complete but it has published articles to reports the

results. The interim cause different authors to produce similar articles. CSE citation

have a benefit that the research is listed according to their first appearance in the

article and the cited article with similar content are placed together. This help the

reader to look up the articles by its content.

In conclusion, the clinical trials are important steps in the development of

oncology and decreasing risks on patients. They also hugely influence the concern on

methodology, the use of statistic data and make the oncologists to use a different type

of citation.
Reference list

1. Prasad, Vinay, and Sham Mailankody. “Research and Development Spending to

Bring a Single Cancer Drug to Market and Revenues After Approval.” JAMA internal

medicine vol. 177,11 (2017): 1569-1575. doi:10.1001/jamainternmed.2017.3601

2. Yamazaki N, Takenouchi T, Fujimoto M, et al. Phase 1b study of pembrolizumab

(MK-3475; anti-PD-1 monoclonal antibody) in Japanese patients with advanced

melanoma (KEYNOTE-041). Cancer Chemother Pharmacol. 2017;79(4):651‐660.

doi:10.1007/s00280-016-3237-x

3 Caroline R, Antoni R, Jedd D et al. Anti-programmed-death-receptor-1

treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a

randomised dose-comparison cohort of a phase 1 trial Lancet 384(2014) pp 1109-

1117

4. Hodi FS, O'Day SJ, McDermott DF, et al. Improved survival with ipilimumab in

patients with metastatic melanoma N Engl J Med. 2010;363(8):711–723.

doi:10.1056/NEJMoa1003466

5. Schachter J, Ribas A, Long GV, et al. Pembrolizumab versus ipilimumab for

advanced melanoma: final overall survival results of a multicentre, randomised, open-

label phase 3 study (KEYNOTE-006). Lancet. 2017;390(10105):1853‐1862.

doi:10.1016/S0140-6736(17)31601-X

6. Hamid O, Puzanov I, Dummer R, et al. Final analysis of a randomised trial

comparing pembrolizumab versus investigator-choice chemotherapy for ipilimumab-

refractory advanced melanoma. Eur J Cancer. 2017 Nov;86:37-45. doi:

10.1016/j.ejca.2017.07.022.

7. C Robert, J Schachter, GV Long, et al.Pembrolizumab versus ipilimumab in

advanced melanoma N Engl J Med, 372 (2015), pp. 2521-2532