Good Clinical Practice (GCP) procedures provide comprehensive moral, ethical and scientific quality rules on how to devise, conduct, assess, audit, record, analyze and report medical trials in an action research project. In addition, GCP ensures that the data and reports generated are accurate and reliable and that the integrity, rights and privacy of the subjects are not compromised (Khosla 1998, p. 24). Granted, there are GCP procedures developed both at national and international levels that stipulate the manner in which to carry out high quality clinical research. The aim of this paper is to examine the moral, ethical and methodological implication of the retrospective use of clinical audit data in clinical trials.
Audit comprises of assessing and monitoring current research practices and comparing performances against existing regulations. It is split into medical and clinical audit, both of which are associated with quality assurance. Clinical audit is carried out by physicians (medical audit) and several other healthcare experts-such as physiotherapists, nurses, speech therapists and occupational therapists. It entails a methodical critical examination of the quality of clinical care. It encompasses gathering data to assess diagnosis and the processes employed for diagnosis and clinical results concerning the treatment, resource use and patient outcome (Bowling 2002, p.8).
The process of audit can be done internally by medical experts who scientifically assess their work or that of external organizations. There are certain conditions that must be met in order to carry out an effective clinical audit. These include: efficient clinical management; basic structures and systems (such as business plan); strategic goal (such as vision, objectives, and tactics); audit personnel and support (e.g. staff recruitment, skilled staff, reward, right skill mix); organizational environment (such as structure and relationship); and training and education (Bowling 2002, p.9).
In addition, the process of clinical audit entails numerous methods. These include: searching and analyzing documents (e.g. studying complaint files, random or methodical selection of medical records for regular assessments); and analysis of clinical case reviews, routine information and presentation made during team gatherings. It also entails the gathering of data from patients in focus groups or via questionnaire where patients’ satisfactions and outcomes are assessed. Although qualitative research methodology is the best in clinical audit procedures, a lot can be gained by complementing it with qualitative methods, for example, observation such as visits to clinics and wards to evaluate quality by watching (National Ethics Advisory Committee 2003, p.3). According to Russell and Wilson, the design of clinical audits should reflect scientific rigor (Bowling 2002, p.9).
Sources of documents and data
All relevant data in original records and endorsed copies of original records of medical findings in a clinical experiment are vital for the reformation and assessment of the action research project (National Health and Medical Research Council 1999, p.3). Original data are found in original and official copies and can be assumed to be the first place where data is captured. On the other hand, original documents that are used in clinical trials include lab notes, hospital records, subjects’ diaries, pharmacy dispensing records, X-rays, magnetic media and other numerous records found in labs and medio-technical departments. The source documents constitute an integral part of the Essential Document that allows assessment of the clinical trials and the quality of the data. Moreover, it ensures that the researchers comply with the guidelines of GCP (Verma 1999, p.20).
Verification of source data
Source Data Verification (SDV) entails an assessment of the compliance of the data contained in case report forms (CRFs) with source data. During this procedure, the researcher’s information in the report is weigh against the original records to make sure that it is accurate, complete and authentic. The main objective of SDV is to make certain that the collected data are trustworthy and permit reconstruction and assessment of the action research project. This means that each element of the data contained in a CRF must be copied somewhere else to facilitate corroboration, audit and restoration. The chief aim of SDV is to verify that the data gathered during a clinical research is comprehensive, correct and legitimate in order to provide assurance to both the regulatory authorities and the sponsor company. In addition, SDV is obligated to offer assurance in any reported data, for instance, at scientific meetings and in published journals. In the absence of SDV all data and research findings of any clinical trials are rendered irrelevant (Khosla 2000, p.181).
One important aspect of clinical research is the privacy of the research subjects, including their classified personal identity and all other related medical data (Nuffield Council on Bioethics 2003, p.1). The appointed researcher and the clinical trial monitor must ensure that all confidential information related to the research subjects’ identities are kept in secret when reading through the source documents. According to the GCP guidelines, any persons (including auditors, monitors, sponsors and other people) with unrestricted access to clinical trial document are required to take necessary precautions within the confines of the relevant regulatory stipulations to ensure that the identities of the subjects and sponsors are not compromised. Informed consent of the patients or subjects must be acquired and documents before the study and a guarantee that privacy will be maintained (Khosla 2000, p.181).
An action research project may entail gathering and preserving personal data related to a person or group. If such information is divulged to third parties, it can cause distress or even harm. Researchers must make plans to protect the privacy of such data by, for instance, excluding data that might result in the identification of the clinical trial subjects or restricting access to the data. With regard to studies that entail collection of data on unlawful activities, such as, use of banned substances, potential subjects must be informed whether the researcher can or cannot protect their identities. When personal identifiers are recorded during the study, the researcher must give a compelling reason as to why this is necessary and provide assurance that such information will be kept in utmost secret. If these data is due for an audit by the relevant regulatory authority, then it should be done by persons who are a professional oath to preserve the subjects’ confidentiality (Moore 2006, p.19).
The researcher must rationalize to an ethics committee if his study entails linkage between records in which subjects are potentially identifiable or are identified. The researcher may be justified to use personal data to facilitate record linkage without consent if: the identity of subjects is not divulged except for the intentions of the record linkage and is immediately destroyed the moment record linkage is completed; if personal data is used with satisfactory security; and the findings from the research will benefit the public. The use of record linkages without precise or supplementary consent is ethically justified especially if audits and other related activities are conducted to ensure delivery of efficient health care services to the public (Moore 2006, p.19)
Custody and archiving
It is the duty of the monitor to make sure that the source data are preserved at the clinical trial site to facilitate corroboration of information contained in CRF. The institution or researcher should preserve the study documents as stipulated in the essential documents. The same should be done in accordance with the pertinent regulatory requirements. The institution or researcher must take precaution to avert premature or accidental obliteration of these documents (Bruckheimer 1993, p.215). The essential documents should be preserved for a period of at least 24 months after the final approval of a promotional application in a region where the ICH Harmonized Tripartite guidelines for GCP apply. However, the essential documents must be kept for an extended period if the sponsor agrees or if obligated by the relevant regulatory statute. The sponsor is required to notify the researcher when to destroy these documents (Khosla 2000, p.181).
Methodology of SDV
There are two main methods of Source Data Verification (SDV). These are: back to back method; and direct method. In the first method, the researcher grasps all the source documents and responds to explicit questions posed by the monitor concerning the data without allowing the monitor to glance at the documents. On the other hand, the direct method permits the monitor to look at these documents. According to the ICH GCP rules, the sponsor has the responsibility to specify the method to be used. He must state clear in either the protocol or documented agreement that the researcher/institution will allow trial-related audits, monitoring, regulatory assessments and facilitating unrestricted access to source data and documents (Khosla 2000, p.184). According to ICH GCP, direct access is defined as consent to inspect, evaluate, verify and make copies of any reports and records that are relevant to the assessment of a clinical trial. The FDA has also noted the relevance of reevaluating the real source of data. It has spotted problems during its reevaluations of copies of data, for example, it discovered cases where names of patients on EKGs and X-rays were deleted and altered to match study subjects. According to the FDA regulations, a researcher is not obligated to disclose the identities of the subjects unless there is need for a comprehensive study of the records related to a particular subject (Bruckheimer 1993, p.217).
Consequences for not performing SDV
The consequences for not carrying out SDV can be very grave. For instance, the researcher is at risk of gathering spurious and erroneous data from which false conclusion are developed. With respect to clinical trials, a moderately small amount of data is collected from a limited number of subjects that can consequently lead to substantial patient exposure if the drug is marketed (Lowrance 2002, p.21). In addition, the dismissal of clinical data by the regulatory authorities if they have doubts on the reliability of the data can result in a denial to award a marketing license. Consequently, this will amount to enormous loss of resources and time to the sponsor company (Khosla 2000, p.184).
Bowling, A. (2002) Research Methods in Health: Investigating health and health services. Philadelphia, Open University Press.
Bruckheimer, M. (1993) FDA’s Inspections of Clinical Investigators. Journal of Drug Information, 27, 213-6.
Khosla, R. (1998) GCP guidelines: differences between the ICH and WHO guidelines. Good Clin Pract J, 3, 24-30.
Khosla, R and Verma, D. (2000) Efficient Source Data Verification. Indian Journal of Pharmacology, 32, 180-186.
Lowrance, W. (2002) Learning from Experience: Privacy and the Secondary Use of Data in Health Research. London, The Nuffield Trust.
Moore, A. (2006) Ethical Guidelines for Observational Studies: Observational research, audits and related activities. Wellington, Ministry of Health.
National Ethics Advisory Committee. (2003) Ethical Review of Observational Research, Audit and Related Activities. Discussion document. Wellington, National Ethics Advisory Committee.
National Health and Medical Research Council. (1999) National Statement on Ethical Conduct in Research Involving Humans. Canberra, National Health and Medical Research Council.
Nuffield Council on Bioethics. (2003) Pharmacogenetics: Ethical Issues. A guide to the report. London: Nuffield Council on Bioethics.
Verma, D. (1999) GCP Guidelines: FDA Vs WHO. Journal of Good Clinical Practices, 6, 18-22.