Introduction

Evidence is information that decision-makers in the health care system can reach, based on a scientific assessment of the practice. It is also a tool that can be used to make sure patients receive the best care available (1,2). Evidence- based practice (EBP) is the process of using the best available evidence to support clinical decisions (3,4). It is also defined as integrating the best research evidence obtained by systematic research into personal experience, clinical decision-making ability obtained by clinical practice, and patient values and preferences (5,6).

Evidence-based nursing is a process in which the evidence obtained from scientific research is  critically evaluated with the participation of the patient according to status, preferences, and availability of resources of patients and healthy individuals to assure the provision of best nursing care (5).  The purpose of EBP is to enable nurses to enrich their clinical training and experience with up-to-date research. EBP enables nurses to learn from many researches, gain knowledge and EBP skills that exist in nursing and enables them to research, evaluate and practice literature in the clinic. It has been reported that experimental studies have increased in the last 20 years and that more than half (67%) of these studies are randomized controlled trials (RCT) (7). RCTs are trials conducted to assess the effects of one or more interventions on individuals or groups. It can also be called interventional trials. These interventions include drugs, cell and other biological products, surgical procedures, radiological procedures, devices, behavioral treatments, changes in care process, and preventive care (8). The importance of RCTs in terms of nursing is that these trials provide the opportunity to draw causal conclusions that will help to demonstrate the effectiveness of the interventions used by nurses. In order to achieve these results, the effectiveness of the initiatives must be demonstrated in a certain system. The synthesis of research evidence using systematic and rigorous methods has become an important feature of evidence-based medicine. It is very important to work with RCT protocols that determine the effectiveness of the intervention to create this systematics (9).

In order to implement EBPs, it is necessary to develop the skills of nurses to critically evaluate research and to establish a culture of basing their practice on scientific knowledge (10,11). Nurses need to know and evaluate the levels of evidence so that EBPs can be transferred to them. Evidence levels reflect how strong the method of studies is (11). Gray and Chambers (12) classified the power of evidence into five categories. Various systems have been developed for the grading of evidence, and evidence and recommendation level classifications adopted by the Joanna Briggs Centre are used for the evaluation of evidence levels in nursing (13). According to the evidence level classification, the strongest evidence comes from at least one systematic review and meta-analysis which are based on well-designed RCTs (14). In evaluating the effectiveness of the initiative, RCT is considered to be the best research design. RCTs shown as evidential source of information provide second level of evidence  in making decision for interventions and are the basic source for systematic reviews and meta-analyses which are accepted to be the first level of evidence for interventions (15). A meta-analysis is a quantitative analysis of the findings of the researches involved in the systematic review using statistical analysis techniques (16). Therefore, the main purpose of systematic review and meta-analysis is to synthesize the results of numerous researches on a particular subject and present the most accurate evidence to health professionals. In these studies, synthesis is mostly performed using the results obtained from RCTs (17). It is very important that RCTs are based on a document called a protocol, detailing the rationale, proposed methods and organization of the intervention (18).

It is possible for nurses to benefit the individuals they care for by using the evidence obtained from the RCTs, if the trials are well-designed and implemented, reported openly and transparently. A well-prepared study protocol is needed to ensure that RCTs, which are a type of clinical research with a high level of evidence, have the chance to be based in clinical practice and directly utilized in decision-making (19). Furthermore, the quality of the evidence obtained from the RCTs depends on the detailed planning of each phase of the study, and the way to obtain these details is through the preparation of a well-planned study protocol (20).

The working protocols prepared with insufficient methodological approach can have high scientific value and appear to be excellent from a theoretical point of view. However, when the study is started, there may be some deficiencies, glitches and inappropriate points. These deficiencies may include who the participants are, which Initiative is targeted, how the participants respond to the initiative is measured, and financial and expert support (21). Proper development, evaluation and implementation of clinical trial protocols is of great importance in avoiding these deficiencies (22,23).

The study protocol is a document that defines the objectives, design, methodology, statistical evaluation and organization of the work to be performed (24). The protocol is a resource that clearly states the logic and structure behind a research project (25). According to another definition, the study protocol is a document that describes each step of the research and answers questions on issues such as what goals the study will achieve, how much power it has (26). In addition, the study protocol demonstrates the guidelines needed to carry out the research. A clinical trial protocol involves processes such as planning, conducting, reporting and transferring the study to practice. A well-written protocol allows evaluation of scientific, ethical and safety issues such as suitability of the study before the study begins, execution of the study, and implementation of the results after the study is completed (27).

It is seen that the culture of planning their study according to the principles of study protocol preparation and continuing their study by adhering to the protocol have not yet become widespread in nursing researchers. A study published in a nursing journal showed that more than two-thirds of the studies published between the years 2011-2016 were not registered and that 54% of them were recorded after the study was initiated. It was also reported that whole study protocol was published in only 9% of the published studies and that vast majority of the published studies lacked of whole study protocol (28). These rates raise the importance of a guideline on the subject. In line with this information, it is thought that the researchers in the field of nursing have insufficient awareness of the importance of preparing a working protocol when starting a RCT. Although preparing a working protocol is a new approach in Turkey especially in the field of nursing, there are hardly any resources that can provide guidence in this regard. In addition, it has become a very important necessity to make registration in the international databases and to take protocol ID before implementation process of the RCT is started, for the studies to be published in quality journals in the future.

The purpose of this review is to increase the level of knowledge at the point of preparing and recording protocols by increasing the awareness of researchers in the field of nursing. In addition, it is thought that this review will provide researchers with guidance on making recommendations and recording the protocol by reviewing the points to be considered during the preparation of the protocol, which is the most important stage of a properly planned RCT process with high evidential value.

Study Protocol Registration, Aims and Benefits

The World Health Organization (WHO) recognizes the study protocol register as the publication of an internationally recognized series of information on the design, conduct and management of clinical trials. Details about the study are recorded in a registration system that complies with WHO standards and this information is published on a publicly accessible website (29). One of the most important journals in the field of nursing recommends that non-registered RCTs should not be published and that the authors’ work could be recorded retrospectively, but that an explanation should be made about the cause. They also stated that it was ideal for the authors to publish the study protocols in a peer-reviewed journal as a full text (28). To register the working protocol in web-based databases means to obtain registration in a way. These registrations involve both the ethical and scientific aspects of the study. At the same time, the registrations provide an ethical function in ensuring that everyone is informed about ongoing and previous work. Many groups including the International Committee of Medical Journal Editors (ICMJE) argue that registrations should be managed by a non-profit organization and free for both registrars and users. Records also contribute to researchers, journal editors, and referees in the context of understanding research results (30).

It is also accepted as a scientific, ethical and moral responsibility. The Declaration of Helsinki states that “every clinical trial must be registered in a public database before the first participant is included in the study.” The objectives of a study protocol are summarized below.

The benefits of registering the working protocols are summarized below.

Study Protocol Preparation Steps and Format

One of the most important stages of working protocol preparation is to obtain a protocol registration number. In order to obtain this registration number, the required information must be entered into the system of the database to be registered after preparing the working protocol in the appropriate format and the compliance of the research methodology must be confirmed through the process of refereeing in the system. In order to present the required information in these databases, it is important to prepare the study protocol in an accurate and valid format for each database. One of the most important and valid of these formats is the study protocol preparation format proposed by the WHO (29,33,34).

The key points of the protocol are that it contains the rationale for why the study is necessary and the detailed plan of the study (25). Therefore, the most difficult stage of conducting a research project is the preparation of a short but comprehensive document (protocol) that clearly outlines the project. The protocols prepared should be accurate, easy to read and free of typos.

It is important to understand the steps in developing a research protocol to accomplish what is planned and achieve reliable results. The extra time spent writing a good protocol will help with the analysis as well as prevent errors at a later stage. If the protocol is poorly prepared or it is not followed, there will be little chance of getting the expected results from the project (31,35).

The format of the study protocol proposed by the WHO in Table 1 is capable of guiding researchers to prepare a good protocol. This table contains suggestions and tips for both the study protocol proposed by the WHO and all study protocol formats available to all researchers. According to the format proposed by the WHO, the study protocols consist of two parts. This table lists suggestions and tips for each section and subsections (20,24,25,31,33,34,36). A similar format is summarized in Table 2 according to the information obtained from more recent references.

Randomized Controlled Study Protocol Preparation Guidelines

RCTs which are transparent, well-designed, well-managed, and based on a good protocol in terms of providing solid evidence, provide solid evidence for use in patient care and health policy decisions. Therefore, careful assessment of the quality of the study is needed before relying on the evidence that RCT provides (37). To make this assessment, the CONSORT (Consolidated Standards of Reporting Trials) report is widely used around the world as a guide for the development of registration of RCTs (38).

Preparing a randomized RCT protocol contains more specific details, unlike reporting RCC results. The EQUATOR web page, which contains quality control lists for each type of research, is widely preferred by researchers on this topic, and contains two guidelines for protocol preparation (39). One of these is the PRISMA-P checklist that researchers can use when preparing a systematic review protocol (40). The other is the SPRIT 2013 checklist. The SPIRIT recommendations are a guide for the authors preparing a RCT protocol. Although randomized controlled study protocols are the basis for study planning, execution, reporting and evaluation, they differ greatly in content and quality. To address this issue, SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) was published in 2013. SPIRIT provides an evidence-based list based on the substances proposed for inclusion in the RCT protocols. SPIRIT 2013 is proposed as a guide for researchers who will prepare a RCT protocol (41).

Accessible Databases Where Study Protocol Can Be Registered

The databases where the working protocol can be registered and the registration number can be obtained are quite varied. The WHO International Clinical Research Registration Platform covers all these databases and collects them all under one roof. Table 3 contains the most commonly used web addresses of these databases and information from The Who’s International Clinical Trials Registry Platform (8,42-44). In the vast majority of these databases, protocols go through the process of arbitration before the registration number is given.

The databases where the working protocol can be registered and the registration number can be obtained are quite varied. The WHO International Clinical Research Registration Platform covers all these databases and collects them all under one roof. Table 3 contains the most commonly used web addresses of these databases and information for The Who’s International Clinical Trials Registry Platform (8,42-44). In the vast majority of these databases, protocols go through the process of arbitration before the registration number is given.

Conclusion

It is thought that the information contained in this review will guide the researchers at the point of preparing RCT protocol. With this guide, researchers will be able to understand the importance and benefits of study protocol preparation and how they should form these steps. They will also be able to access the necessary information for the registration of the study protocols they have created.

Writing a detailed protocol that contains all the correct and necessary steps is an important step before starting study. The protocol should be written simply and accurately, but clarify all aspects of the protocol. For this purpose, the use of the study protocol preparation format proposed by the WHO provides both ease in registering the protocol of the study and allows to describe the design and course of the study in detail.

From an ethical point of view, the Declaration of Helsinki also stresses that study protocols must be registered in a public database. Researchers are advised to evaluate the study protocols according to their internationally valid check lists before registering and to register the study protocols in international databases. The registration number obtained from these databases will be included in the protocol part of the study, and when researchers reach the publication stage, this condition will be used by many quality journals. A RCT based on the study protocol preparation steps will be a good source of evidence for use in EBPs and will contribute to the improvement of the quality of RCT and the increase of the value of evidence.

Ethics

Peer-review: Internally peer reviewed.

Authorship Contributions

Concept: A.D.A., Z.Ö., Design: A.D.A., Z.Ö., Analysis or Interpretation: A.D.A., Z.Ö., Literature Search: A.D.A., Writing: A.D.A.

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The authors declared that this study received no financial support.