Clinical protocol trial

A protocol should be clear, concise, and well-planned. Some considerations for planning a clinical trial protocol involve the entire study team. It is very important to consider the time required for all assessments to be completed by the study staff as well as the participant s.

For outlining procedures that will take place during individual study visits, it is critical to ensure that the description of the flow of visits in the protocol makes sense. Ideally, the procedures to be conducted at each visit should be listed sequentially. This provides more linear guidance to the staff who will be conducting the trial.

It will also help guide the creation of other documents required for clinical trials, such as Case Report Forms CRFs and the proposed monitoring plan. As is the case with any other document or publication, appropriate reference annotation is essential. Reference styles may differ between organizations, but generally any widely accepted reference style that is used in scientific publications is appropriate to use in a clinical trial protocol.

References are usually used in the Background section of a protocol, providing any details about previous research done on the investigational product or related substances. This section helps to lead the way to explaining why this clinical trial will further prove any previous hypotheses.

It is important to note that when designing a protocol, you want to set yourself up for success. Protocol Deviations are sometimes necessary while conducting a clinical trial. Deviations can be major or minor, but they are important to document irrespective of their severity. The primary endpoint is 3-year OS rate.

The OS will be estimated from the operation day to the date of death or last follow-up. The key secondary endpoints are QoL and nutritional outcomes. It consists of 40 items in 11 domains and its scoring ranges from 0 the worst to the best for each domain.

The summary score for KOQUSS, defined as the mean of eight equally weighted symptom domains, will be calculated in each case. Scoring ranges from 0 the worst to the best for functional scales and from 0 the best to the worst for symptom scales. The 3-year disease-free survival DFS , 3-year recurrence-free survival RFS , 3-year gastric cancer specific survival and 3-year postrecurrence survival are also included as secondary endpoints.

DFS will be calculated from the operation day to the date of event occurrence or date of last follow-up. The events for DFS include recurrence of the primary tumour at the resection margin or a distant organ, metachronous cancer in the remnant stomach, newly developed cancer in another organ and death from any cause. For RFS, the events include recurrence of the primary tumour at the resection margin or a distant organ and death from any cause.

The postrecurrence survival is defined as the time from recurrence to the date of death from any cause or last follow-up. In addition, subgroup analyses will be conducted by pathological stage stage II vs III , extent of gastrectomy distal vs total gastrectomy and adjuvant chemotherapy received vs not received.

Each endpoint will be compared between the 3-month and 6-month groups in specific subgroups, and favourable follow-up intensity for each subgroup will be determined. Clinical research coordinators of each of our site will be trained in using iCReaT system before initiating data entry and will enter the data according to standardised data entry guidelines. Regular review of eCRFs will be performed by the data management team and all errors will be sent out to each site as queries.

Regular data monitoring for each site will also be conducted. An independent data monitoring committee IDMC will be organised by independent experts who will not participate in this trial. IDMC will monitor the overall process of the trial including safety data. A total of events are needed to detect this difference with an alpha error of 0.

Both intention-to-treatment ITT analysis and per-protocol analysis will be conducted, and the primary analysis will be performed in the ITT population. The survival rates will be estimated using the Kaplan—Meier method and the differences between survival curves will be tested using the log-rank test.

The QoL scores are non-normally distributed and differences in QoL between the two groups at baseline or any specific time point will be assessed via the non-parametric Wilcoxon rank sum test. The differences between overall QoL scores over time will be evaluated using a linear mixed effect model. Nutritional outcomes will be determined using repeatedly collected continuous variables such as QoL scores.

Statistical analyses will be performed using SAS V. No patients or members of the public were involved in the design, or conduct, or reporting or dissemination plans of this research. The STOFOLUP trial is an investigator initiated, randomised controlled trial involving 16 institutions in Korea, and the first large-scale prospective trial with regard to surveillance after curative gastrectomy for gastric cancer, worldwide.

In this trial, we will determine whether frequent surveillance tests are associated with survival benefits or improvement of QoL in patients with gastric cancer.

The results of this trial will provide high-level evidence and will affect actual follow-up schedules in clinical practice. Several retrospective studies on surveillance after curative gastrectomy for gastric cancer have been reported.

In a review article analysing nine retrospective studies, six of nine studies compared patients with symptomatic recurrence with those with asymptomatic recurrence. Although there is no well-designed prospective study for patients with gastric cancer to date, a large-scaled randomised clinical trial comparing more frequent follow-up testing with less follow-ups has been performed in patients with stage II or III colorectal cancer COLOFOL trial.

In its final analysis, frequent follow-up testing did not produce a significant rate reduction in the 5-year overall mortality and colorectal cancer-specific mortality. The present study was designed with reference to COLOFOL trial with regard to the difference in OS rate between the two groups, and the follow-up interval was decided by referring to a previous nationwide survey study. Most responders Thus, we planned to conduct a comparison between the 3-month and the 6-month groups.

Short-interval surveillance is associated with early recurrence detection; consequently, DFS can be affected by lead-time bias. Therefore, the primary endpoint was decided as OS in this study. We will also evaluate postrecurrence survival, which has been reported to be longer in patients with asymptomatic recurrence than in those with symptomatic recurrence in previous studies.

QoL is one of the most important clinical outcomes in cancer patients. Timely and appropriate symptom management can improve QoL, which is another key purpose of regular surveillance. Nutritional status after gastrectomy has been evaluated in many previous studies.

The effect of follow-up interval on nutritional status is another important endpoint of this study. Frequent CT scans augment exposure to radiation and increase the risk of adverse effects of contrast media. The effective dose for single abdominal CT is approximately 10—15 mSv.

Considering that the effective dose limit for radiation workers is mSv for 5 years in the Republic of Korea, reducing the frequency of CT scans as much as possible is necessary. Although the incidence is very low, severe adverse effects of contrast media, for example, anaphylaxis shock, must be considered as well. Thus, the results of this study can provide important evidence for risks and benefits depending on the CT follow-up interval. This study has some limitations. First, the follow-up interval can be modified during adjuvant chemotherapy, which can diminish the differences between the two groups.

Physical examination, laboratory tests and prescriptions for adverse effects of chemotherapy are not limited during adjuvant chemotherapy and additional CT checks for oncological evaluation are also allowed during adjuvant chemotherapy.

Second, detailed management methods for postgastrectomy symptoms and nutritional support methods are not standardised among participating hospitals. In practice, the severity of symptoms cannot be classified into standard categories and its management strategy widely varies.

Each physician and hospital have their own strategy or policy. Turning Discovery Into Health. This protocol template aims to facilitate the development of two types of clinical trials involving human participants. NIH developed a second protocol template to help behavioral and social science researchers prepare research protocols for human studies measuring a social or behavioral outcome or testing a behavioral or social science-based intervention.

Drafting the protocol correctly will increase the likelihood that the conclusions drawn from the research are scientifically sound. Recommendations and suggestions should be sought from colleagues and experts so that researchers can develop their plans.

However, once the study is launched, the protocol should not be altered during the progression of the study or trials. If the changes during progress of study are minor, then that part of the study should be excluded from the analysis. Unless unexpected complications occur during the conduct of the trial, it is advisable to reconsider and rewrite the protocol where the whole process is started again provided that the original research topic is still considered to be relevant.

If complications are anticipated, it is suitable to run a pilot study, to check the feasibility of the study and find answers to the potential areas of the trial. Clinical trials must be approved and monitored by an Institutional Review Board that ensures that the risks are negligible and are worth any potential benefits.

It is an independent committee that consists of physicians, dentists, statisticians, and members of the community. The committee ensures that clinical trials are ethical and that the rights of all participants are protected. The board must initially approve and periodically review the research. Protocol writing allows the researcher to review and critically evaluate the published literature on the interested topic, plan and review the project steps and serves as a guide throughout the investigation.

The proposal is an inevitable document that enables the researcher to monitor the progress of the project [ 5 ]. What is the study about, Who are the targets, Where is the setting of the study and When it is launched, if applicable-. It should make the main objective clear, convey the main purpose of the research and mention the target population. Carry maximum information about the topic in a few words; it is a good practice to keep the title to within words.

It should convey the idea about the area of research and what methods are going to be used in a compact, relevant, accurate, attractive, easy to understand, and informative way.

Contents page list of relevant sections and sub-sections with corresponding page number. Signature page is signed by senior members of the research team and dated to confirm that the version concerned has been approved by them.

Contact details for the research team members listing postal, e-mail addresses and telephone numbers. In writing the review, attention should be drawn to the positives, negatives and limitations of the studies quoted [ 7 — 9 ]. Introduction is concluded by explaining how the present study will benefit the community.

The literature review should logically lead to the statement of the aims of the proposed project and end with the aims and objectives of the study. The review should include the most recent publications in the field and the topic of the research is selected only after completing the literature review and finding some gaps in it. The research question should be described precisely and concisely. It is going to be the basis of designing the project. The definition of the problem should be clear so that a reader can straight forwardly recognize the real meaning of it.

These should be confined to the intention of the project and they should arise from the literature review. State the goal you need to achieve. They are answers to what are the possible responses to the research question or hypothesis under analysis and measure. Aims should be logical and coherent, feasible, concise, realistic, considering local conditions, phrased to clearly meet the purpose of the study and related to what the specific research is intended to accomplish.

For example, to evaluate knowledge level regarding dental caries in primary school children in KSA this is not detailed. The following should be added: Causes, treatment, preventive measures, etc. Specific Aims: Details of each objective that will finally lead to the achievement of the goal should be stated.

Specific aims one by one should be listed concisely. It is good practice not to include too many aims in the study best ; too many objectives often lead to inaccurate and poorly defined results. Furthermore, aims should be achievable, realistic and specific with no general and ambiguous statements. They should be stated in action verbs that illustrate their purpose: i. Secondary Objectives Optional : These are referred to as ancillary and minor objectives that could be studied during the course of the study.

The formulation of objectives helps to focus the study and to avoid the collection of any unnecessary data and hence organize the study in clear and distinct stages.

Hypothesis: It is a statement based on sound scientific theory that recognizes the predicted correlation between two or additional assessable variables [ 11 ]. It is always developed in response to the purpose statement or to answer the research questions posed.

Furthermore, hypothesis transforms research questions into a format amendable to testing or into a statement that predicts an expected outcome. Null hypothesis: A null hypothesis is a statement that there is no actual relationship between variables H0 or HN.

It may be read as there is no difference between the groups to be compared and no relationship between the exposure and outcome under investigation. H0 states the contradictory of what the researchers expect. The final conclusion of the investigators will either keep a null hypothesis or reject it in support of an alternative hypothesis. It does not essentially mean that H0 is accurate when not rejecting it as there might not be an adequate proof against it.

Alternative hypothesis: An alternative hypothesis is a statement that suggests a potential outcome that the researcher may expect H1 or HA. This hypothesis is derived from previous studies where an evident difference between the groups to be compared is present. It is recognized only when a null hypothesis is rejected. Practically, hypotheses are stated in the null form, because they have their inferential statistics.

Such hypotheses of no difference will be challenged by researchers and the result of the statistical testing gives the probability that the hypothesis of no difference is true or false [ 12 ]. Aims should be logically linked and arranged according to the tested hypothesis statement.