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All information these cookies collect is aggregated and therefore anonymized. Cookies are used to deliver many types of targeted digital marketing. It is a good practice to have these items but it is more ideal to have hand-written notes explaining the consent process. Ultimately however, it is the PIs responsibility to ensure that proper consenting takes place. In an audit situation, they would have to defend their SOP so remind them of that. I hope that addressed your question.
Here is another post you might enjoy: link to Sponsor Furnished Source Docs. Could you please tell me what is your opinion about creating source documents for clinical trials and keeping it separate from the usual practice medical records. What do you think about this?
Is it mandatory to have the same type of source documents for patients in clinical trial as medical records in standard practice? I am presently interning with a Clinical Research Training Institute online, and this is a very resourceful tool. Thank you so much! So happy I found this blog! One question, as a CRA, would you be concerned if source data was being recorded in a word document on a desktop computer by the Study Coordinator, then later printed out for PI signature.
Hi thanks for a great question that I adapted into a new post. Is there any legislation which confirms this audit finding? Thank you. You must be logged in to post a comment. In this open platform clinical researchers exchange ideas, publish and share information, and benefit from these collective resources.
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L-legible, can I read this? C-contemporaneous, was this recorded at the time of trial conduct or later? O-original, is this unaltered or copied? Telephone contact log.
Generic SOP template. Meeting Minutes Template. Concept protocol — template. Protocol feasibility checklist. Protocol feasibility assessment SOP. Risk assessment template. Clinical study report template. Budget Monitoring tool. Budget Monitoring tool with example data. Essential documents checklist.
Trial Master File Contents List. Archival of essential documents SOP. Archiving trial data SOP. Enrolment log. Screening SOP. Subject identification log template. Recruiting study participants SOP. Subject screening log template. Follow up visits SOP. Subject visit log vaccine trial. Pre and post admission study team meetings SOP. Subject visit log any trial. Blood Sampling SOP.
Subject withdrawal and termination log. Pre-screening eligibility check template. Transfer of patients SOP. Screening procedures. Interviewer recruitment log. Participant communication log. Interviewer follow up form. Informed consent template - generic. Audiovisual recording of informed consent SOP. Informed consent template for clinical trials. Reviewing and obtaining informed consent SOP.
Informed consent template for observational in-patient clinical trials. Informed consent template for interviewing research studies. Informed consent template sampling only.
Monitoring informed consent checklist. Subject informed consent log template. AudioViual recording informed consent checklist. Opinion leader inputs - meeting records. Informed Consent Sample only in household community. Concomitant medication log. It is the expectation of the GCP Inspectors' Working Group that investigators are aware about the location of the source data and consistent in recording them.
The intended location should be clearly defined prior to subject recruitment. One way of achieving this is to generate a source data location list. This list should be prepared by the site and should be signed and dated by the principal investigator or by a person whom the principal investigator has assigned this task. The list should be filed in the investigator's trial master file. As the location of source data could vary from one investigator site to another, it could be appropriate to make the list site specific.
In order to facilitate location of data, the list of source data should be sufficiently detailed. It is often not enough to write 'medical record', as the medical record is often a collective name covering different document types and locations. This may make it necessary to write: 'patient record — dispensing and administration chart', 'medical record — continuation', 'medical record — nurses notes', etc. It is frequently seen during GCP inspections that the CRF is designed to only include an overall statement regarding a subject's eligibility in the trial.
The text in the CRF could for instance say: 'Did the subject satisfy all study entry criteria? The statement is typically intended to be answered with 'yes' or 'no'.
The expectation of the GCP Inspectors' Working Group is that adherence to all individual inclusion and exclusion criteria are documented in the source data. Adherence to the criteria of the protocol can originate from different sources like blood samples, physical examination, medical history, information from the subject etc. When designing the protocol and the related CRF, the sponsor should carefully consider where each source data originate from, with reference to a specific visit. This is important since some data originate from screening visits, others from the randomisation visit and some data could be historical.
It should be agreed with the investigator of a site how adherence to the individual criteria is documented. It is the expectation that a qualified physician who is an investigator or a sub-investigator for the trial has assessed each individual eligibility criteria and has taken the final decision to include the subject in the trial ICH GCP 4.
This decision should be documented prior to the subject receiving the first dose of the IMP. GCP inspections have revealed a substantial amount of cases where the overall eligibility statement in the CRF confirms subject eligibility but where source data shows that the subject did not fulfil all eligibility criteria.
It therefore seems that a system with an overall statement in the CRF regarding a subject's eligibility in itself does not ensure the safety of the subjects, the quality of the data and sponsor oversight. The requirement for investigators to keep a copy of the CRF has been in existence for 20 years. This requirement is valid irrespective of the media used; however, the introduction of electronic CRFs in clinical trials presents an additional challenge in achieving this requirement - especially if data are being submitted directly via a web based application.
Requirement 10 of the above reflection paper states the following: "The sponsor should not have exclusive control of a source document. The 12 requirements in the reflection paper originate from the CDISC standard and are therefore quoted directly in the reflection paper.
However, although the CDISC requirements specifically relate to source data, the requirements is considered by the EU inspectors to be also applicable to transcribed data - as stated in the reflection paper section 6.
Therefore, the requirement of a contemporaneous and independent copy of the CRF is valid irrespective of whether the CRF contains source data or only transcribed data.
The EU GCP inspectors do not consider the requirement above to be met if data are captured in an electronic system and the data are stored on a central server under the sole control of the sponsor. This is because the investigator does not hold a contemporaneous and independent copy of the data.
It is the responsibility of the sponsor and the investigator to institute a process by which a contemporaneous and independent copy of the CRF is available at the investigator site.
If the blinding is prematurely broken, it is the responsibility of the investigator to promptly document and explain any unblinding to the sponsor ICH GCP 4. The medical care of the trial subjects includes medical decisions such as whether to start or stop treatment or institute alternative treatment if required.
Consequently, in order to do so, the investigator must have unrestricted and immediate access to break the treatment code. Some sponsors have recently introduced a code breaking system that requires the investigator to contact a sponsor representative and only after discussion with the representative, the investigator receives information that unblinds the treatment.
Some sponsors have even added a requirement that the investigator submits a written form after the phone call before receiving the information that unblinds the treatment. Consequently the sponsor can't require or insist on being involved in the decision to unblind, stall or delay in any way the unblinding of trial subject treatment in emergency situations. The groups also strongly recommend that any sponsor who has introduced or is applying such a system should immediately revise it in order to be compliant with international guidelines.
Breaking the treatment code is usually conducted via code envelopes or electronic systems such as telephone or web based systems such as IVRS and IWRS. When using these kinds of systems the investigator must have direct access in order to break the blind without the interference of the sponsor in any way.
In support of electronic systems, a backup system enabling unblinding of treatment must be provided. The CTFG and the GCP IWG acknowledge that such backup systems are operated by the sponsor in a manual way and that the investigator or other treating physician can contact the sponsor staff to unblind the treatment.
Still, the sponsor is not entitled to stall or reject unblinding. Code breaking instructions should be specified clearly in the clinical trial protocol. Prior to such GCP inspections, the European Medicines Agency EMA sends an announcement letter to the applicant in which — among others — a list of documents to be provided to the inspection team is presented. The data are used by inspectors for review in order to select patients and data to inspect.
Among the requested documents are the individual patient data listings for the patients recruited at the sites to be inspected. Based on past experience, this request for data listings poses a significant number of problems and subsequently costs a lot of time for companies and inspectors, quite often resulting in listings of suboptimal quality. It is important to emphasise that the following guidance is the expected standard for most inspections; however, for some trials different, specific requests may be warranted.
Consequently, no data should be provided until contact has been established with the reporting inspector and the requirements for data listings have been discussed. Unless otherwise agreed with the inspection team, the data should be collected in the groups defined below — each to be presented in a different Excel spreadsheet. If in doubt, please ask the lead inspector:. Sponsors contract out an increasing number of tasks in clinical trials.
This applies in particular to the safety of the subjects and the reliability and robustness of the data generated in the clinical trial. Therefore, very often, sponsors delegate related tasks to third parties. In these cases, sponsors remain responsible to conduct the trial in compliance with the protocol and with principles of good clinical practice Clinical Trials Regulation Art 47, ICH E6 R2 section 5. During good clinical practice GCP inspections of commercial as well as academic trials, an increasing amount of deviations from GCP standards have been identified by the inspectors in view of sub-standard contractual arrangements and related procedures.
Special consideration should be given on relevant training and quality systems. Experience suggests that vendors accepting tasks regarding electronic systems are frequently knowledgeable about IT systems and sometimes data protection legislation, but not necessarily on ICH E6 R2 requirements, quality systems, etc. The examples of deviations are described as bullet points under the following headings: status of contracts, distribution of delegated tasks, standards to be followed, audits and inspections, serious breaches, compliance with the protocol, output and exemptions.
The following contract-related issues have been identified by GCP inspectors in the context of clinical trial inspections:. Due diligence should be exercised from the sponsor to ensure that the distribution of tasks is clearly documented and agreed by the vendor, and that each party has the control and access to the data and information that their legal responsibilities require. The following issues have been observed by GCP inspectors regarding certain standards to be adhered to by the vendor.
When the vendor fails to formally agree to comply with the applicable national and EU legislation related to the conduct of clinical trials , as well as with ICH E6 R2 requirements, the sponsor should consider whether the use of the vendor is appropriate for the clinical trial.
It is sometimes not stated that the sponsor should have access to conduct audits at the vendor site and that the vendor site could be subject to inspections by national and international authorities and shall accept these. In addition, it needs to be specified that vendors shall provide necessary documentation e.
It is frequently not specified in the contract that the vendor should report potential serious breaches to the sponsor for assessment and onward reporting and reporting timescales for such reports are missing.
Some contracts reviewed had inconsistencies between the protocol and the wording of the contract. Examples have also been seen where contracts referred to the version of the protocol applicable when the contract was signed, however there was no contractual requirement to cover the vendor obtaining any subsequent changes.
There is a risk that the vendor could implement changes to the electronic system based on protocol amendments sent by the sponsor that have not been approved by the CA and REC. The contract or the vendor procedures should address how this would be prevented. In terms of output generated from the clinical trial , the following observations have been made by GCP inspectors:.
It is important to be aware of any exemptions in the contract regarding specific functionalities of the data collection system. For example, contracts stating, that a data collection system cannot be used in the handling of e.
On the basis of recent GCP inspection findings, inspectors would like to reiterate that sponsors should contractually ensure:. The system in question may be a system validated by the supplier, but installed at the sponsor, or a system provided as software-as-a-service SaaS or cloud solution. Today, in clinical trial settings, the use of electronic systems, e. A considerable number of electronic Case Report Forms and applications for e.
Furthermore, it is specified that the approach to validation should be based on a risk assessment that takes into consideration the intended use of the system and the potential of the system to affect human subject protection and reliability of trial results. This risk-based approach should be informed by the following guidance given. The risk assessment should be justified by the sponsor and documented. The sponsor is ultimately responsible for the validation of the clinical trial processes, which is supported by electronic systems and for providing sufficiently documented evidence to GCP inspectors on the validation process and the qualification of the electronic systems.
The sponsor may rely on qualification documentation provided by the vendor if the qualification activities performed by the vendor have been assessed as adequate. Documentation regarding the validation of processes and qualification of systems is considered essential by GCP inspectors and it is likely to be requested during inspections.
In case a sponsor has relied fully or partly on vendor qualification efforts and documentation for any system function, the sponsor should make sure that such documentation is readily available for inspection if requested. Failure to provide access to the documentation is likely to result in critical findings that will impact the acceptability of the clinical trial data. A sponsor should amend any contract with vendors to ensure availability of qualification documentation.
If a vendor is not willing to amend the contract, the sponsor is responsible to demonstrate that the system concerned is in a validated and qualified state. In case the trial is ongoing, this should be done without delay; if the trial is completed, this should be undertaken prior to the submission of the MAA.
The required migration of previously captured clinical trial data should be validated. Findings that are the responsibility of the sponsor are still likely to be issued for the lack of documentation and inadequate vendor assessment prior to trial initiation.
The GCP-IWG is of the opinion that the ICH -GCP guideline and applicable EU laws do not prohibit such practice, but it should be clear who has the responsibility for all aspects of subject protection and data reliability and robustness and the procedures in place should ensure that the rights, safety, dignity and well-being of subjects are being protected and the data generated are credible and accurate.
The sponsor of a clinical trial may, in particular cases, consider necessary to provide the investigational site with personnel to be involved directly in the conduct of the clinical trial.
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