Why is it sometimes difficult to enroll subjects?

The trial protocol should strictly define what subjects can be enrolled (enrollment criteria) and what subjects cannot be enrolled (exclusion criteria). The inclusion / exclusion criteria should be strictly checked when selecting patients. If unqualified subjects are enrolled, they will not only deceive the ethics committee, but also will not be compensated by the sponsor once the subjects have drug-related adverse reactions. In addition, when applying for new drug marketing license to the administrative authority with this test result, the application will be rejected because unqualified subjects are enrolled in the group in violation of the test plan.

There are many ways to enroll subjects. In the trial of healthy subjects (phase I trial), researchers can be recruited by advertising in local newspapers or journals. In the United States, people have started to advertise on the Internet to recruit subjects. You can also consider radio or television advertising. Most institutions will conduct regular physical examination of healthy volunteers to maintain a list of volunteers that can be used at any time. Keeping a diagnosticindex (DI) is another effective method for screening the eligibility of subjects to participate in a trial. Di is a document or computer system that simply records the names and characteristics of patients. By inputting some keywords that meet the enrollment conditions, the system searches for patients that can be used for screening. Although the use of Di is time-saving and convenient, it is not an effective method for researchers conducting routine trials. Other methods that can be used to enroll subjects include:

·Post notices in the outpatient or operating room;

·According to the gender / age registration form, send email directly to the possible subjects;

·Universal screening of all visiting patients (for example, in a hypertension trial, blood pressure was measured in all patients ≥ 40 years old);

·Waiting for qualified subjects to come to the clinic (such as infected patients);

·Establish specialist and specialized disease clinics (such as asthma clinics). GCP requires that all methods used to recruit subjects should be approved by the ethics committee before implementation, and should be approved in writing by the Ethics Committee for the finalization of advertisements and notices.

The methods of enrolling subjects in the trial varied.

Sometimes all subjects can be determined before the start of the trial, and sometimes subjects must be gradually enrolled as the trial progresses. In the latter case, whether the research center can accurately predict the number of subjects is crucial. If the enrollment work is delayed so that the sponsor cannot complete the enrollment plan within the specified time, it will cause great difficulties for the implementation of the next trial. The delay of enrollment will delay the whole process of new drug research and development, and eventually lead to the delay of new drug marketing time.

There are many reasons for the difficulty of incorporating derivatives, which can be divided into three categories: problems of the test itself, problems of the research center and some unforeseen reasons.

Some common reasons are listed below:
Test own problems;

Problems under study;

Unforeseen causes;

The test plan is not practical;

The investigator did not have enough time;

Changes in hospital management system;

The test plan is inconsistent with the routine operation;

Other test personnel are not interested in the test, change work or cannot undertake additional work;

The start of the trial is delayed, such as the approval of the ethics committee is delayed, and the drugs for the trial are not delivered on time.

Patient enrollment criteria are too strict;

Incomplete test facilities and instruments or missing subjects;

Personnel changes or deficiencies hinder the smooth progress of team entry;

Patients were excluded from the trial due to taking prohibited concomitant medications;

Some beds were cancelled at the last minute due to the general lack of human resources;

TV / journal coverage of trial sites, researchers, sponsors or clinical trials;

Subjects were unwilling to participate in the trial due to lack of interest in the nature or evaluation of the trial;

Another competitive trial was conducted at the same center at the same time;

Subjects with too long trial period were not suitable for treatment in this center

Indications are extremely rare;

The number of subjects was incorrectly estimated or the required patient type could not be found at the selected trial site.