clinical trial conduct

Question 1

What is the goal of a clinical trial?

Answer 1

A clinical trial is conducted to acquire data to inform the public, regulators, researchers, patients, and healthcare professionals of the effects a drug/intervention may have. An aspect of this is the collection of data and correct management, processing and evaluation. As a result, there are various QC regulations ensuring this is effectively achieved.

Question 2

What is GCDMP?

Answer 2

These are guidelines outlining Good Clinical Data Management Practices. These should be followed to ensure correct database design and testing, data collection and tracking, and data validation and cleaning.

Question 3

What are examples of the guidelines of GCDMP?

Answer 3

1. Clinical data management professionals should be familiar with the data privacy laws which exist within the regions a clinical trial is taking place.
2. Should design all clinical data collection tools (e.g. case report forms, lab databases) so that minimal identifiable characteristics are included.
3. Every study should have a data management plan to promote high quality data and you must ensure that all stakeholders are familiar with and understand the data management plan.
4. The DMP must be properly signed for and approved before any data collection takes place.
5. CRFs should be designed based on the data specified by the protocol.
6. CRF design, development, approval should be documented.

Question 4

When does clinical trial data collection start?

Answer 4

Data collection begins with the participants giving written consent. This must be recorded and retained.

Question 5

What are source documents? Give examples.

Answer 5

Source documents are the original documents in which data was recorded, e.g. hospital charts, patient questionnaires, X-rays.

Question 6

What is a case report form?

Answer 6

A case report form is a document which comprises data of a subject from the study. It is essentially the required information needed to be reported to the sponsor for a particular study subject.

Question 7

What is electronic data capture?

Answer 7

This is a system that is used in clinical trials to collect clinical trial data in an electronic form, rather than paper form.

Question 8

What are the advantages of using EDC?

Answer 8

It promotes for efficient and faster access to data, e.g. edit checks can be programmed into the software to ensure any outlying data is picked up and queried. Also, it ensures that clinical trial personnel from various sites have immediate access to the data if needed, ensuring faster data analysis, etc. However, it is important to note that EDC is still an early system therefore optimisation is still required. You may find that some sponsors still use paper formats just incase. There must also be a security system in place to ensure no unauthorised access is gained.

Question 9

What is the role of the site monitor?

Answer 9

The site monitor acts on the sponsor’s behalf and may liaise with the study sites to ensure protocol compliance, competent regulations are followed, and ICH GCP is adopted at all. Any queries may be followed up by the Sponsor.
They also ensure that adverse events are reported correctly, CRF data is consistent with source documents, and errors and discrepancies are resolved.

Question 10

What are the 2 types of data management QC audits?

Answer 10

Critical and Non-critical

Question 11

What is a critical variable audit?

Answer 11

This is when 100% of the data is checked and errors are corrected. Focus is on the critical variables associated with looking at efficacy and safety. Assure data quality.

Question 12

What is a non-critical variable audit?

Answer 12

Data is checked at a lesser rate. The error rate is calculated and all errors are corrected.

Question 13

What is database locking?

Answer 13

This occurs at the end of a clinical trial when no more data is to be collected. The database is locked preventing the input of anymore data sets. This ensures a clean, uniform final document with no variation, for optimal analysis.

Question 14

Why do we have eligibility criteria?

Answer 14

Eligibility criteria allows us to define the target population but reduce the amount of variation in the study without threatening the scientific integrity of the trial.

Question 15

Why might patients get involved in trials?

Answer 15

1. Clinical trial may provide another option for patients, when the standard options have not been effective or exert intolerable side effects.
2. People may want to contribute to the advancement of medical knowledge.
3. Patients may believe that the treatment is the best available, therefore want to be involved in a trial where they could potentially get the treatment.
4. There may be a stipend involved.
5. Care givers want the best possible treatments to be available to them.

Question 16

How do patients find studies?

Answer 16

1. Internet resources
2. Doctor
3. Newspapers
4. TV
5. Pharmacist
6. Nurse
7. Someone else with same condition
8. Pharmaceutical companies (via brochures, etc.)
9. Support groups

Question 17

Why might volunteers not be accepted onto a trial?

Answer 17

They may not meet the eligibility criteria, or the number of participants needed may have already been met.

Question 18

What are the challenges for recruiting patients to a study?

Answer 18

1. Often investigators may feel pressured to recruit participants in as short amount of time as possible, as the cost of delayed enrolment is huge.
2. There are multiple clinical trials going on at all times therefore there can be huge competition.
3. Patients have access to a lot of information on the web which may be incorrect and fear them into not participating, especially due to previous scandals.

Question 19

What are the ICH rules and regulations for recruiting subjects?

Answer 19

1. The investigator should be able to demonstrate potential for meeting the required number of subjects
2. They required EC approval of subject recruitment procedures, e.g. advertising used to ensure no coercion.
3. They required that site monitors must track and report the subject recruitment rate.

Question 20

What are the ICH guidelines for patient compensation?

Answer 20

Any amount or method of payment to subjects must be reviewed by the ethics committee to ensure there is no coercion or influence on subjects. They also ensure that payments are prorated.

Question 21

What roles do the ethics committee play in recruitment?

Answer 21

The ethics committee has a huge role in patient recruitment - they must review and approve the recruitment strategy. They must determine whether it is coercive, whether vulnerable populations are targeted, and if so they must be protected at all costs. They then must ensure that the advertisement of the trial is appropriate and states the benefits and risks without over/understating.

Question 22

What are the recruitment methods which are allowed?

Answer 22

1. A healthcare provider may talk to a patient about a study and collect information in preparation for research trial, however patient must know this.
2. Healthcare records may be reviewed by study staff, however this should be included in part of the sites privacy agreement, and information should not be taken outside of this site.
3. Patient may contact a researcher (through internet, etc.)
4. Advertising (as long as budget allows it)

Question 23

Who is involved in recruitment?

Answer 23

This may vary between trials.

1. Study coordinator
2. Investigator
3. Recruitment coordinator
4. Research Assistant

Question 24

What is central advertising in clinical trials?

Answer 24

Central advertising is a system to aid the ease of participant recruitment. After advertising campaigns are released, there must be a site governed by staff which is available to receive calls/emails, etc. from patients wishing to participate in a study. Leads can be sent online to the different trial centres involved.

Question 25

What is the best way to achieve successful recruitment?

Answer 25

Protocol design must include patients of the relevant study population. EC require documentation to prove the protocol design prior to approval and authorisation. It also benefits the clinical trial personnel as it allows you to gain an understanding of the relevant patient population, e.g. what is the best way to recruit these patients, where, how many?

Question 26

What should be the recruitment plan?

Answer 26

1. The potential number of subjects that a site might enrol to the study
2. The best methods for recruitment
3. A realistic budget
4. Advertising materials and approval
5. Must implement the recruitment plan after it is approved
6. Must continually evaluate the recruitment performance (site monitor can do this)
7. Limit the protocol complexity

Question 27

How can you estimate the number of subjects you might enrol in a particular site?

Answer 27

You can review what is known about a patient population, e.g. use the inclusion/exclusion criteria to determine how many patients within the A&E unit of Newcastle RVI would be eligible to take part in the study per month, etc. Can also speak to physicians and how many staff you have that are available.

Question 28

Where can you register clinical trials in the UK?

Answer 28

In the UK we have the ‘UK-based International Standard Randomised Controlled Trial Number (ISRCTN) Register. This registration is required for all MRC-funded trials. The UK Clinical Research Collaboration (UKCRC) was also established to promote the awareness and wealth of clinical research. You can register clinical trials with the UKCRC.

Question 29

What are good ways to ensure subject retention?

Answer 29

1. You must ensure that you build a good relationship with the study subject. You must encourage feedback and create the impression that the subject is important in this trial.
2. Have short waiting times
3. Have more interesting waiting rooms, is there things there they can read, snacks, drink, watch TV etc.
4. Reimburse travel, provide food vouchers, etc.
5. Can find ways to show appreciation, e.g. research newsletters to keep them updated, holiday cards, etc.

Remember if a subject is satisfied they will stay in the study, and may even ask about future ones.