Guidance to Research Ethics Committees on Initial Facility Assessment

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EFGCPIECsiteassesdocFINAL4Dec2009 Page 1 of 11

Guidance to Research Ethics Committees on Initial Facility Assessment

Introduction

One of the roles of a Research Ethics Committee is to provide an opinion on a proposed study, based on the suitability of the facilities and the investigator concerned. In order to assist REC members in their assessment of a facility, the following checklist has been provided by EFGCP. It is intended as guidance only, and a negative response to any of the items should not be automatically construed as a reason to decline a proposed study. Of far greater importance than the completion of the checklist, is the determination of the relevance and importance of any of the individual items mentioned in the checklist to the study and facility in question.

It may be appropriate for a sub-committee to review the facility initially and subsequently periodically to determine compliance against the specific requirements of each protocol.

Ethics Committees in the European Union have a requirement for assessing the suitability of clinical research centres. Individual Member States may differ in their requirements for what Ethics Committees should include in their assessments. EFGCP does not seek to replace or contradict any Regional, National or Local regulations or guidelines, but to put forward some suggestions for “best practice” to Ethics Committees and their regulating authorities.

It is intended that this document should be completed by appropriate site staff as an aid to the Research Ethics Committee in fulfilling their duties in assessing site suitability prior to providing approval for a clinical trial to be conducted.

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EFGCPIECsiteassesdocFINAL4Dec2009 Page 2 of 11 European Regulatory Background.

2001/20/EC 2005/28/EC ICH GCP (E6)

EMEA Procedure Number INS/GCP/3 on Conducting GCP Inspections (Annex 5- Phase 1 units)

EU Commission Detailed Guidance on the Application Format and Documentation to be Submitted in an Application for an Ethics Committee Opinion on the Clinical Trials on Medicinal Products for Human Use ENTR/CT 2, Feb 2006 (*)

Ethics committees have obligations to assess qualifications of Investigators and supporting staff and quality of facilities for clinical trials (*)

4.7 Suitability of the Investigator and Quality of the Facilities

The qualification of the principal investigator should be described in a current curriculum vitae and/or other relevant documents. Any previous training in the principles of GCP or experience obtained from work with clinical trials and patient care should be described. Any conditions, such as economic interests, that might be suspected to influence the impartiality of the Investigator should be presented. The Ethics Committee should give an opinion on the quality of the facilities (including the availability of adequate resources, personnel and laboratory facilities). The evaluation of the quality of the facilities might be based on a written statement by the head of the clinic/institution at the trial site or by some other responsible person, according to the system in the Member State.

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What are the factors that need to be considered by the IEC when reviewing a research facility?

The following are a list of factors to be considered by an IEC. This list is not exhaustive but suggests areas to consider: Does the IEC perform qualification reviews on a per study basis?

Does this depend on the phase of study being considered? How often are reviews of research facilities being conducted?

Do procedures exist to outline documentation requirements, review cycles, etc? Are there procedures for actions following IEC reviews of a research facility?

Template Checklist to assist IECs in their review of research facilities

A checklist has been devised to assist IECs in their review of research facilities. This has been subdivided into areas that should be assessed, for example, the qualification of investigators and their supporting staff, the quality of the facilities etc. the IEC may also like to consider the requirement of other study approvals, for example approval from a bio-safety

committee. The checklist provides details on the types of questions that need to be raised as part of the process for

understanding the capabilities of the research facility. The document could be forwarded to the site for their completion prior to IEC review. If the IEC regularly works with a particular facility then this document would not need to be fully completed each time – only some sections may be applicable. The questions need to be carefully assessed and further follow up may be required. The level of due diligence performed by the IEC is entirely at their discretion.

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Template Checklist

Areas of Review

Yes

No

N/A

Comments

Qualifications of Investigators and

Supporting Staff:

How are identities known (per study)?

Are current CVs for all personnel involved in study available for review?

Are licences available?

What is the history of clinical research experience? Is there insurance coverage?

Does the PI have a locally recognised medical (or dentistry) qualification?

Are position descriptions available for all staff? Does the site have Policies for being informed of changes in study staff? For all- i.e., those listed on delegation log?

Is there a training program for all staff members- induction and continuous?

Are there training records available? Is GCP training included?

When were staff last trained in GCP?

Has training been conducted for handling of hazardous substances?

Where are these documents retained? Is there a policy for updating?

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Areas of Review

Yes

No

N/A

Comments

Qualifications of Investigators and

Supporting Staff (cont.):

Has the investigator (and staff) been the subject of an investigation by a regulatory authority?

Are there any conflicts of interest which can be professional or personal (i.e. investment or proprietarily rights in the study sponsor)?

Per study- has it been assessed if the PI will provide adequate oversight and backup including appropriate delegation of responsibilities and training?

Has time availability been assessed (e.g.,

participation in competing and noncompeting trials)? Does the site have adequate resources?

Can the required number of subjects be recruited within the time frame specified by the Protocol? How is 24/7 coverage maintained?

Who can the subject contact outside of business hours?

Quality of Facilities

:

Is the phase and nature of a study considered- e.g., Phase 1, inpatient, outpatient?

Are study specific requirements considered such as access to radiology equipment, remote data capture, access to pharmacy and laboratory facilities,

freezer/equipment requirements etc? Where are subjects being assessed?

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Are satellite sites being used?

Areas of Review

Yes

No

N/A

Comments

Quality of Facilities (cont.)

:

Pharmacy

Is there a clinical research pharmacist? What is the procedure for receiving study medication?

Is study medication ever relabelled? If so, is there a Quality Control process?

How about dispensing or manipulation in case a manufacturing license is required?

Where is study medication stored? Is access controlled?

If refrigeration or freezer required- what are the temperature monitoring and calibration/maintenance procedures?

Are there alarm procedures-e.g., central, out of hours?

Are there procedures for reconstitution and dispensing of study medication?

What are procedures for destruction of study medication?

Are records maintained? Is there an archival policy?

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Areas of Review

Yes

No

N/A

Comments

Quality of Facilities (cont.)

:

Clinical Equipment

Are there calibration and maintenance records for all equipment- e.g., centrifuges, IV pumps, ECGs, EEGs, scales, clocks?

Are there CPR trolleys?

How/where is resuscitation equipment stored? How often are the contents reviewed for expiration dates?

Where is the equipment retained and for what time period?

What other maintenance/validation checks performed?

Laboratory

How are staff trained on protocols?

What type of equipment is used for analyses? What processing of samples occurs?

Raw data- reporting of results, computer systems used- types of systems, validation, security (physical and electronic), access descriptions – please define. What are the procedures for disaster recovery (back up procedures)?

Is the laboratory involved in QC procedures- e.g., accreditation and QA/QC schemes?

Are there any alternative procedures (e.g., malfunctions)?

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Areas of Review

Yes

No

N/A

Comments

Quality of Facilities (cont.)

:

Other facilities

What other facilities are being used i.e. imaging?

Subject recruitment and obtaining informed

consent:

Are the IECs being informed of recruitment procedure- e.g., advertising, databases? What safeguards are there for participation in

multiple research studies- regardless of phase? E.g. maximum of studies per year, limits on blood

withdrawals, informing GPs if applicable? What reviews are conducted of obtaining compensation?

What methods are used in obtaining consent? What is the role of the legal representative? Who has been defined in this role?

What is the process to involve this person should the need arise?

Source Documents & Medical Records:

If paper based source documents, are there policies for ensuring that all are accurate, legible,

contemporaneous, original, attributable, complete, consistent, enduring and available when required? Are there policies for archival, access, retrieval and retention?

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Areas of Review

Yes

No

N/A

Comments

Source Documents & Medical Records

(cont.):

If computer based records are relied upon as source documents, what are the types of systems,

validation, access descriptions, procedures for disaster recovery (and back up procedures) and security (physical and electronic)?

Privacy and Confidentiality

Policies- do any exist for paper copies and computerized systems?

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What additional factors need to be considered for Phase I facility assessments?

When assessing Phase I facilities it is important to consider EMEA inspection procedures INS/GCP/3 Annex 5. Additional to the „Template Checklist‟ provided, the following points also need to be considered:

Basic and advanced life support training (permanent and contract temporary employees)

Availability and maintenance of emergency procedures and equipment

Procedures in case of an emergency and agreements with local hospitals for any services provided

Volunteer Care

- Procedures for testing for use of illegal drugs - Measuring protocol compliance

- Subject monitoring

- Facilities for meals and preparations - Leisure facilities for overnight stays - Subject identification during stays

- Provision of emergency contact numbers Recruitment and Consent

- Recruitment strategies

- Volunteer database (including if facility staff can participate) - Collection and verification of volunteer histories and identities - Monitoring of “over-volunteering”

- Contacts with GPs (family doctors) - Routine screening procedures

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