1 ) What do you think are the most important qualities of being a CRA ? How would you define a good CRA ?
1) Careful and rigorous, and have the ability to deal with emergencies;
2) Good medical professional knowledge, familiar with GCP, English up to CET-6, and have the ability to learn and master new knowledge quickly;
3) Good and efficient communication skills, the ability to work independently, and the spirit of teamwork.
The excellent CRA should add to the above:
1) Sincere love for clinical research and continue to work hard for it;
2) More than 3 years of CRA work experience in an excellent company (Fortune 500 or excellent CRO), and completed more than 2 clinical trials;
3) Solid and rich medical professional background and continue to pursue further education in this field. .
2 ) How are hospitals screened?
(My understanding is how do you determine if the sites in the base are suitable for conducting their own clinical trials?)
4 main factors are referenced:
1) whether the center's principal investigator or investigators have the relevant qualifications and experience (including familiarity with clinical medications and GCP training, etc.);
2) whether there is enough time to complete the trial on schedule;
3) whether there is a sufficient source of patients to complete enrollment on time;
4) whether there is sufficient equipment and instruments for the trial.
Reasonable cost, good cooperation, reliable quality, easy to check the travel, help the registration to pass smoothly, and help marketing.
Comply with the duties of clinical investigators required by GCP; have sufficient time to ensure the implementation of the trial; be interested in the research value of the clinical trial program of my new drug, and treat the trial as a serious and conscientious scientific exploration activities; be able to complete the subject entry program on time; should not be involved in other competing trial programs of new drugs for the same disease at the same time; be honest and decent, rigorous work, and team security.
3 ) GCP Basic Principles?
Principles of ICH GCP
1 Clinical trials should be conducted in accordance with ethical principles derived from the Declaration of Helsinki, consistent with GCP and applicable regulatory requirements.
2 Before starting a trial, the foreseeable risks, inconveniences, and expected benefits to individual trial subjects and society should be weighed. A clinical trial should be initiated and continued only when the expected benefits outweigh the risks.
3 The rights, safety, and health of the trial subjects are the most important considerations and should prevail over the interests of science and society.
4 The non-clinical and clinical information available on the medicinal product being tested should be sufficient to support the proposed clinical trial.
5 Clinical trials should have a strong scientific basis and a clear, well-described trial protocol.
6 The clinical trial should be conducted in accordance with a trial protocol that has been approved/endorsed in advance by an Institutional Review Board (IRB)/Independent Ethics Committee (ICE).
7 The duty of a qualified doctor or qualified dentist is always to give medical care to the subject and to make medical decisions on behalf of the subject.
8 Each person involved in the conduct of a clinical trial should be qualified by education, training and experience to perform his or her intended task.
9 Free and informed consent should be obtained from each subject prior to participation in a clinical trial.
10 All clinical trial data should be recorded, processed, and stored in a manner that permits accurate reporting, interpretation, and verification of the data.
11 The confidentiality of potentially identifiable subject records should be protected, respecting privacy and confidentiality in accordance with applicable regulatory requirements.
12 The test drug shall be manufactured, handled, and stored in accordance with applicable Good Manufacturing Practice (GMP). The test drug should be used in accordance with the approved protocol.
13 A system of procedures should be in place to ensure quality in all aspects of the trial
4 ) What measures are taken when patients are slow to enroll?
Regarding progress, there are two problems: slow progress; and progress is uneven across centers. (Fast progress naturally does not become a problem)
1. Slow progress
The solution to slow progress depends on the reasons that lead to slow progress, some people think that slow progress is that there are fewer patients, and there is nothing that the monitor can do about it. In fact, we can analyze the various reasons for slow progress and some of the ways that may be conducive to solving it:
< strong> 1.1 No patients.
No patients is a phrase often used by researchers. For us monitors, it is important to note that this statement can be true or false. In the case of a false statement, which we will discuss below, let's look at the case of a true statement first. Even if it is true, it is important to note that it is not necessarily true. The reason for this is that just because the researcher who said this has fewer patients does not mean that the center has fewer patients. Perhaps the researcher you are looking for is participating in your study on a personal basis, i.e., he is the only one who collects cases, and it is possible that he may not be enrolling patients every day or most of the time, but may be attending surgeries, or maybe he sees patients two half-days a week in an outpatient clinic (which is what we have encountered). At this time you have to investigate the situation, so go to the monitoring can not say just go to the director, looking for ordinary doctors who do not participate in the trial, and even look for nurses will help you understand the necessary information, for example, you can know whether there is no patients, patients at what time, which season is more patients, patients and what kind of main such as local, or foreign? Naturally, it is not easy to enroll foreigners in the group. After understanding, if you think there is a possibility to promote the progress, you need to mobilize the whole department, and even the enthusiasm of the nurses (this is actually very easy), the work is done y, to this point, the progress will come up.
Another reason is that the investigator's ability to persuade is poor, or he or she does not recognize the drug or the study, such as thinking that the study is a test with patients. The real situation is: it is not that there are no patients, but the patients are not willing to enroll. This time you need to do a lot of persuasive work, do clinical trials less centers pay attention to training in advance is essential, must reflect the characteristics of the drugs used in the study (each drug has its own characteristics), if you can't do this, you can only impress the researchers in other ways. At the same time, as an investigator, he or she must agree with the study and be justified in doing so. In fact, many of our domestic clinical studies are on drugs that have already been marketed in foreign countries, and in many cases, they are geographical and ethnographic validation studies. Another approach is to offer compensation to patients in order to promote enrollment. We should be careful about this approach. It is not to say that money should be given. If a group of mainly students is given money and it is thought that it may promote enrollment, then it may be worth a try, but in other cases, caution should be exercised. This is because Chinese people can reason with each other without giving money, but if you do, the patient will think you are cheating him, and will have the Chinese suspicion that "there must be nothing good in it". But it's not to say that you can't give, you can consider some small gifts, or even some printed materials about the disease, such as diet, life should pay attention to all aspects (this is sometimes a good method, you may want to try it).
Let's consider the real situation: there are really no patients, and the center (the department, not just the researchers) just has few patients. There are deeper reasons, such as the center is not strong academically, the number of beds in the wards is not enough, the volume of outpatient visits is small; and it is past the season of high incidence. Many diseases are seasonal, and although they are not typical, they actually have a great impact on research. For example, in antibiotic clinics, respiratory tract infections are better enrolled in the fall and winter. Another example is seasonal allergic rhinitis. This should be taken into account before the implementation of the project, and arrangements should be made in advance, so as not to be in no hurry in the preparatory stage, and then rush desperately later on, which is a waste of energy. Even holidays should be taken into account, such as the traditional Chinese festival: the Spring Festival, as a project executive, you have to spare at least a month's time. If your data entry is done by a student or you hire a statistician to do it, then you should factor in the two summer and winter vacations, if the budget coincides with the completion of the case observations and the need to do the entry work at that time. Of course, in addition to the above, there are other factors that affect the absence of patients, such as a hospital move (don't think it's rare, it may have happened to someone), or refurbishment of a ward. All of these factors, unless they can be anticipated and prepared for in advance, have to be dealt with in other ways. Adding a center is an option, but it requires a new filing and an ethics clearance (depending on the rules of the lead hospital, sometimes only a filing is required, as adding a center is not a major factor in the ethics review).
Recruitment advertising. Recruitment advertising can be divided into two types: in-hospital and out-of-hospital (I named it myself, lol). In fact, outside the hospital refers to the media, generally more cost-effective is the print media, such as newspapers. Yard on the name, but we can expand it. As for how to expand the I'm here to sell a secret, leaving you a space to think about it.
1.2 Robbing the patient (no patient falsehoods)
Robbing the patient is the most common situation in reality, but also the most headache situation. First of all, there are a number of drugs for the same indication at the same time in a center. For example, antibiotics, which have been developed more in the past few years, include cephalosporins, quinolones, and aminoglycopeptides, all of which are aimed at the same patient group: respiratory tract infections and urinary tract infections. If one is a tablet and the other is an injection, it's okay. This is because tablets tend to enroll patients with mild infections. If several of them are injections, then it is a big problem. There are also several manufacturers of the same drug in the same center to do. Although this situation is not allowed by the state, but still in. This is because there are just too many manufacturers that are approved, such as parzufloxacin. If this situation is detected in the preparatory phase of a project, it needs to be considered: do we need to change the site? Can the clinical department control it? How should it be controlled? Is the source of patients mainly inpatient or outpatient? Are there enough beds? To paraphrase: "early detection, early prevention, early treatment", huh (not much can be done!). . If it is found in the project stage, it should be clear that CRA is essentially a service. Monitoring is the purpose, but not the method. The same variety, to put pressure on the clinic, because this is not allowed by the relevant regulations. For different varieties but for the same indication, there cannot be more than three. Whether you can change it or not, you have to take it seriously and do a good job of getting the investigators to recognize your work, and there are not many ways to do that, but that's the heart of it.
2. Uneven progress. That is, some centers are fast, some are slow.
Transfer cases. This situation occurs in the center of the regional group randomized design, large center randomized design will not appear (that is, the centers do not have a fixed number of cases of random, but by telephone and other means to arrange the random number with the drug, at present, this kind of random to do less). Transferring cases raises several questions:
How many cases are transferred?
How many cases are guaranteed to be statistically significant in slow-moving centers?
How to transfer?
Generally it is block randomized, so the number of cases transferred is also transferred between centers in block numbers. The purpose is to ensure that the ratio of trial to control in each center after transfer is 1:1, and there is no fixed number of cases that should be transferred. However, the number of cases in each center should not be too small, and if it is too small, the significance of multi-center clinic will be lost. Note: The significance of a multicenter clinic is to ensure the diversity of sample sources. What is the minimum number of valid cases in a sub-center to be statistically significant? Note: There is no requirement that every center be statistically significant. There is no longer a requirement to write a sub-center summary report (but a sub-center statistical report is required). Centers with a small number of cases can be statistically described only. However, it is not possible to have 40+ cases in one center and only 4 cases in another.
It is also important to note that statistical significance is not the same as clinical significance. The absence of statistical significance is not the same as the absence of clinical significance, but it depends on how it is interpreted and how the program is designed and the characteristics of the type of disease being treated.
Remember: the purpose of multicenter is to ensure the diversity of sample sources. You can't transfer cases to a multicenter clinic to lose the significance of multicenter.
5 ) What are the documentation requirements for starting a clinical trial?
Documentation requirements for initiating a clinical trial (I think this question can be used to answer the question "What are the main documents of a clinical trial"):
1) Approvals (SFDA approvals, IEC approvals)
2) Trial documents (trial protocol, ICF and recruitment, advertising and procedural protocols, etc., CRP) Advertisement and procedure protocol, etc., CRF, IB, and all relevant revisions and additions that have passed the ethical)
3) Signed contract (investigator's contract, financial regulations)
4) Medication List (list of drugs received for the trial and distribution record sheet, etc.)
5) Laboratory documents (normal value ranges, quality control certificates, etc.)
6) Investigator CVs, registration forms and related documents
7) Your own company's forms and practices (monitoring reports, monitoring registration forms, etc.)
6 ) Difference between Adverse Reactions and Adverse Events?
The key difference between the two is whether or not they are related to the drug being tested. Adverse Event (AE): An unforeseen medical event that occurs in a subject during a clinical trial, but is not necessarily causally related to the drug used. Events can be symptoms, signs, laboratory abnormalities, and a temporary illness that may be related to the drug used in the trial. Adverse Drug Reaction (ADR): a harmful reaction unrelated to the purpose of the medication or unintended that occurs under normal usage and dosage of a qualified drug. When an adverse event is evaluated and determined to be related to the drug being tested, it is called an adverse drug reaction.
7) How can CRAs assist investigators in retaining subjects?
This has a lot to do with doctors and the government. In the study I am monitoring now, there is a big difference between different sub-centers in the same region, and in the same city, where the culture and the values of medicine are the same, there is a big difference between two adherence rates. In one case, adherence was even less than 20%, while in the other there was not a single case of dropout or loss of visits. The reason for this lies with the doctors. First, whether the hospital has established a better follow-up system, some hospitals will require patients to return to the outpatient clinic for follow-up on a regular basis or from time to time, while some do not care whether the patients come back at all. Second, is the hospital doctor's own medical quality, its medical level is not high people simply will not return. Third, is the doctor's level of communication and the degree of relationship with patients, this on the one hand depends on the doctor's medical ethics, on the other hand, to see its ability to communicate, there are doctors can basically do to patients and pleasant, at least the patients will not resist; can be some of the whole day gloomy face, it seems that everyone owes him money, look at it is not happy, the patient will not be hanging him after discharge. Fourth, the patient's awareness of regular outpatient clinics or doctors to do, which is the popularization of basic medical awareness, doctors are duty-bound. Fifth, the government (real health insurance and real people's hospitals). Sixth, the government (so that the people have money and real purchasing power).
8 ) What are the responsibilities of the researcher, and the monitor?
What are the duties of the researcher?
1) Familiarize themselves with the protocol, implement the clinical trial in strict accordance with the protocol, and participate in revisions to the protocol if necessary;
2) Familiarize themselves with the characteristics and usage of the trial drug;
3) Assist the sponsor in obtaining IEC approval;
4) Be responsible for obtaining informed consent signed by subjects;
5) Ensure that the trial site is in good condition, including adequate personnel and appropriate facilities;
6) Have a sufficient number of patients to complete subject enrollment on time;
7) Have sufficient events to complete the clinical trial in a quality and timely manner and to submit a qualified and accurate report of the clinical trial (for multicenter trials, the principal investigator is responsible for the completion of the report) Of course, the investigator must (For multicenter trials, the principal investigator is responsible for the completion of the reports.
What are the responsibilities of the monitor:
I. Trial preparation to confirm that the site is ready to conduct the trial:
Staffing and training, adequate equipment, adequate patient care, and familiarity of the investigator with the trial medications, clinical protocols, and related documents
II.
1) Formulation of the visit plan
2) Confirmation of the signing of the ICF by the subjects, to understand the current status of the enrollment and the progress of the trial,
3) SDV: to confirm that the trial data and the CRF filled in the true, complete and accurate, the preservation of the original documents
4) Confirmation of the AE and SAE records and compliance with the requirements of the report
(5) verification of test drugs: whether the storage, distribution and recovery in accordance with the provisions, and detailed records
Third, the end of the trial recovery of drugs, preservation of test data, to assist in reporting the trial data and results of the purpose of supervision:
1) to ensure that the trial in accordance with the clinical protocols, GCP and the relevant regulatory requirements
2) to protect the The rights and safety of the subjects
3) The data recorded and reported in the trial are true, complete, accurate and consistent with the original information
9 ) How are the trial drugs managed in the trial? When is the trial drug allowed to be sent to the hospital?
1) Strict management: to ensure that it is for the use of the subject only, and to ensure subject compliance through drug counts.
2) Dedicated staff: Designated personnel by the principal investigator to manage and keep detailed records of the receipt, distribution, storage, recall and destruction of the drugs (including positive controls and placebo). Drugs should be kept in a place where safety box storage conditions are met. In double-blind trials, it should be ensured that the drugs are issued in randomized numbered order.
3) Effective counting: at the end of the trial, subjects were asked to return the remaining drugs and boxes of used drugs for counting. Only after obtaining SFDA approval and IEC approval can the trial drug be sent to the hospital.
10) How is the protocol designed? What are the components of a protocol?
A clinical trial protocol consists of: a protocol is a document that describes the purpose of the trial, the design, the methods, the statistics, the implementation, and usually also gives the background and theoretical basis of the trial. In short, a protocol describes in detail how to conduct a clinical trial, including the purpose and design of the trial, enrollment and exclusion of patients, safety and efficacy evaluation criteria, how to take the drug, how to analyze the data, and how to deal with adverse reactions.
11 ) Difference between serious adverse event and severe adverse event ? How is it reported?
A Serious Adverse Event is a medical event that is difficult to manage at any dose, whether or not it is related to treatment.
Includes:
1) Death;
2) Life-threatening;
3) Resulting in hospitalization of the patient or prolonged hospitalization;
4) Resulting in permanent or severe disability/functional impairment;
5) Resulting in congenital anomalies/teratomies, affecting the ability to work or, resulting in congenital malformations;
6) Other.
Reporting of SAE: In addition to taking immediate emergency treatment measures for the subject, the investigator must report immediately to Sponser, IEC, and within 24 hours to the SFDA Division of Safety and Security, which is usually required by the SFDA Division of Registration.