Question17: What are some of the important points that should be considered during study Initiation?

1)      Professionalism

Prefessionalism is the first thing that is expected from a CRA in relation to study monitoring.It is very important for CRA to look and act professional.CRAs can get off to a bad start because of the way they work and dress. The CRA should wear appropriate business attire and should always arrive at the site on time or a little early. The CRA must remember that he or she is an official representative of the sponsor and should always behave in an appropriate business-like manner.

Monitoring requires a lot of unsupervised time “on the road .There are many temptations when traveling that can distract a CRA from work – shopping, museums, television or the latest bestseller but CRA should act in a professional manner and should not let hum self get distracted.

2) Excellent Communication Skills:

A CRA must determine how to integrate telephone, email, fax and regular mail communications into a monitoring strategy. This will differ for different programs and sites. It will depend on the technologies available, sponsor and site Standard Operating Procedures (SOPs) and personal preference, both at the site and at the sponsor company. In monitoring, like any business, many problems can be traced back to a lack of communication, inappropriate communication and/or unclear communication. A good communication strategy should have a high priority in CRA monitoring plan.

3) Good Observation Skills:

There are a number of general things the CRA will want to be aware of when monitoring a site, including interpersonal relationships, the stability of the staff, organization, how site personnel manage their time, and an overall impression and feeling about the site. The reason for this is that the atmosphere at a site affects the study. The better it is, and the smoother things run, the better the study will go.

It is important for a CRA to be observant. Do people get long well with each other? Do they work together? Are there obvious antagonisms, one-upmanship, etc? If one person is very busy, do others help out? If there are problems, the CRA may need to work around them in order to achieve the monitoring objectives.

4) Problem Solving Ability:

Another CRA responsibility is problem solving. Things rarely go exactly as planned, and clinical trials are no exception. The CRA must be prepared far a variety of potential problems such as enrollment difficulties, personnel turnover, waning interest in the study by site personnel, poor conduct of the study and protocol violations. Experience, knowledge and good common sense are CRA best tools for problem solving. If there are problems with site management, the CRA may have to monitor more often to ensure that the study is run properly and that things get done in timely manner.

5)Time Management:

A CRA will need to develop an overall “hands on” monitoring strategy for site visits. In general, it is best to start with the most important activities, or at least the ones that must be done at each visit. This will ensure that is time runs short and everything cannot be completed, at least the most important things will have been reviewed.

It is expected from a CRA to make monitoring plan consistsing of the following activities, done in the order listed:

• Serious adverse event review
• Informed consent review
• Checking protocol adherence
• Case report form review and source document review
• Queries and error correction
• Investigational product review and accountability
• Review of laboratory samples
• Study document file review

  Serious Adverse Event Review

One of the first things a CRA should do at each monitoring visit is ask the investigator and coordinator if there have been any serious adverse events since the last visit, and if there have been, if they were reported to the sponsor. e CRA should examine the information available about the events, including a review of the patient chart and any supporting documentations. If additional information is available that has not gone to the sponsor, the CRA can gather it and ensure that it is submitted to the appropriate person at the sponsor in a timely manner.

  informed Consent Review 

At each visit, the CRA should check the informed consents for each new subject enrolled since the last visit. Informed consent forms should be signed and dated by the last visit.

  Checking Protocol Adherence

Checking protocol adherence it something the CRA should check when monitoring each subject’s dataTo ensure adherence, the CRA will want to check the following items:

Subject eligibility. Did the subject meet all the inclusion and exclusion criteria?

Randomization. Was the subject randomized to the correct subject number and did he or she receive the appropriate packages for investigational drug?

Protocol activities. Were the correct activities done for or by the subject at each visit?

Visit schedule and windows. The visit window is the number of days around the actual projected visit date when the subject can be seen. The window is usually the date plus and minus a number of days.

         Case report form review

When review the case report form for a subject, the first thing to do is check each single page. The CRA should check for completeness, ensuring that each item has been completed and each blank is filled in. Are the forms legible?

The CRA should think about what appears in the forms, and whether or not it makes sense, given the subject condition and the study activities. If something does not make sense, the CRA should discuss it with the study coordinator and/or investigator

         Source document review

Source document review, sometimes called source document verification, involves checking the data recorded in the case report forms against data found in available source documents, including the patient chart, laboratory reports and other supporting documents.. A source document is any document where the data are first recorded.

The purpose of source documentation is twofold: first, to verify that the subject exist and, second, to verify that data in the CRF are consistent with the information found in the source documents, which verifies the integrity of the data.

         Errors, queries and corrections

Perhaps the most important errors a CRA might find are those that result in protocol violations. These include such things as a subject not meeting the inclusion/exclusion criteria, a wrong diagnosis, a subject taking disallowed medications, problems with visit windows and others.

The CRA should note them in the corrections/questions log and discuss them with the study coordinator. When they are resolved, the coordinator should make the necessary corrections to the case report forms; CRAs do not make the corrections. Corrections are made by drawing a line through the incorrect entry, making the correct entry and dating and initialing it

6) Confidentiality

During all monitoring activities, the CRA must be attentive to confidentiality. No study record, other than the consent form should identify the subject. The CRA has an obligation to help protect the confidentiality of all study subjects. The study documents are also confidential. During site visits, sometimes CRAs have seen competitor’s protocols lying around unprotected. All one needs to see is the protocol cover page to know the name of the drug and phase of development. The CRA should periodically remind the investigator and coordinator of the confidentiality of these documents, and ensure that they are kept in a secure location.

It is also the responsibility of a CRA to make monitoring visit report at the end of each visit. The purpose of the monitoring visit report is to document the findings from the monitoring visit. The CRA should use this from to summarize what was done at the investigative site, including CRFs gathers for shipment to the sponsor. This is also where problems must be documented, including what was done to solve them, or to make recommendations of action items for the next visit.