Quality Assurance In Clinical Trials Research Articles

Variation in mantle technique: implications for establishing priorities for quality assurance in clinical trials

74 European and American radiotherapists responded to a questionnaire investigating the treatment of a patient with stage IIA non-bulky Hodgkin's disease by mantle irradiation. A consensus was present for the dose aims to involved and uninvolved lymph nodes and the acceptable incidence of late normal tissue effects. There was less agreement as to the total dose and dose per fraction required to maintain normal tissue toxicity within the agreed acceptable incidence. Variation was found in the radiation technique employed, the amount of spinal cord shielding used, the prescription point, modifications if irradiation was given after chemotherapy, and the routine recording of dose and dose per fraction to the normal tissue at risk. This descriptive survey confirms the need for well designed quality assurance programmes and indicates the areas of particular uncertainty that currently exist.

Management of quality assurance in clinical trials

Good Clinical Practices (GCP) were first established by the FDA and are now actively implemented by different countries. This becomes necessary as multinational large clinical programs are more complex, involving a large diversity of personnel and locations, with different practices of medicine and local regulatory requirements. The responsibility of an independent Quality Assurance (QA) organization is to oversee the quality and integrity of research activities, and to assure compliance with company's regulatory requirements, and ethical considerations in order to facilitate worldwide registration of new compounds. The goal of a Clinical QA group is to provide continuous assistance to monitoring teams and investigators to ascertain authentic and reliable clinical trials. The Clinical QA programs must be flexible, calling for active communication and good understanding of quality requirements. Clinical auditing is one of the instruments of Clinical QA. Study audit activities begin with the protocol, encom...

Quality assurance for intraoperative electron radiotherapy clinical trials: Ionization chamber and mailable thermoluminescent dosimeter results

Ionization chamber and thermoluminescent dosimeter measurements were made to verify the dosimetry data provided to the Radiation Therapy Chart Review office of interinstitutional electron intraoperative radiotherapy clinical trials. The ionization measurements included intraoperative radiotherapy applicator output and depth dose measurements made at the stated 80% and 50% depths at 14 different radiotherapy facilities. Mailable thermoluminescent dosimeter measurements, including output and depth dose measurements were made at 16 institutions. The mailable thermoluminescent dosimeter results show similar inter-institutional agreement, both for output and depth dose comparison, with the corresponding ion chamber results for intraoperative radiotherapy applicators. These results are compared to similar measurements made for conventional electron applicators.

A Quality Assurance Program for Sponsored Clinical Trials

Clinical trial quality assurance audits are performed to ensure that studies were conducted in the manner prescribed by protocol (and described in the final study report); that proper attention was given to subject rights and medical research ethics; and that the data from those trials are accurate and properly documented. The auditing approach that we have found to be most successful consists of evaluating the systems for conducting and controlling clinical trials, and performing detailed audits of specific studies identified as critical to supporting claims of drug safety and efficacy. Study audits involve reviewing all in-house study documentation to identify and select those parameters that are best indicative of subject eligibility, proper adminis­ tration of the protocol medication, proper and timely execution of protocol required tests and measures, and accurate reporting of test results. Data for these parameters are then analyzed to detect questionable trends and patterns. Following this analysis, specific cases and data points are selected for verification against on-site source documents.This technique has proved very successful in identifying problems that could effect the interpretation and acceptability of sponsored clinical trials. We believe that these clinical study audits can, in addition, make a significant contribution to the support of well-conducte d trials, and potentially, to expediting regulatory approval of applications for research or marketing permits.

Quality Assurance of Clinical Trials and Good Clinical Practices in France

Several years ago, US companies with subsidiaries in France initiated the implementation of Good Clinical Practices (GCPs). In late September 1987, the French Medicines Division of the Health Ministry published the “Bonnes Pratiques Cliniques” (BPCs). These official recommendations, the first to be issued in a European country, define the objectives for all parties involved in a clinical trial. The French BPCs are a series of measures that define the responsibilities of sponsors and investigators “to ensure the quality and authenticity of scientific data.” The development of standardized procedures will facilitate the application of BPCs. These guidelines suggest a regular quality verification performed by the sponsor with maintainance of the corresponding reports. This could be confirmed through audits to verify the conduct of studies and also evaluate the authenticity and reliability of the data before submission for registration. Inspectors from the Ministry of Health will control the conformity of BPC...

Evaluation of pathology review of malignant lymphomas and Hodgkin's disease in cooperative clinical trials. The Eastern Cooperative Oncology Group experience.

Although central expert pathology review for quality assurance in cooperative clinical trials involving malignant lymphomas and Hodgkin's disease was put in place by the NCI two decades ago, its impact upon patient eligibility for given treatment protocols has never been assessed. We reviewed diagnoses from contributing pathologists, the Eastern Cooperative Oncology Group (ECOG) review pathologists and the Pathology Panel for Lymphoma Clinical Studies in 2019 cases from 14 ECOG protocols. Although we found high rates of disagreements in diagnoses, the vast majority of these represented differences which did not impact on protocol eligibility. A total of 221 cases (10.9%) were excluded from protocols, representing a range of 2.8 to 36.7% of cases per protocol. Eighty-six percent of the exclusions resulted from the initial review by the ECOG hematopathologists. Our data indicate that while central pathology review is mandatory for quality assurance in malignant lymphoma (ML) and Hodgkin's disease (HD) protocols, a two-tier review mechanism is not necessary for adequate quality control.

Statistical and empirical evaluation of histopathologic reviews for quality assurance in the Eastern Cooperative Oncology Group.

Central pathology review for quality assurance in cooperative clinical cancer trials has been an accepted practice for over a decade. However, the actual value of such pathology review has never been statistically evaluated or the need defined in a comprehensive manner. Pathology exclusions in 35 completed and ongoing Eastern Cooperative Oncology Group (ECOG) trials were analyzed. Ineligibility rates ranged from 0% to 16.9%. The lowest ineligibility rates occurred in breast cancer, small cell and non-small cell lung cancer, squamous cell carcinoma of head and neck, and gastrointestinal carcinoma protocols. The highest rates occurred in rare cancers such as malignant thymoma, endocrine carcinomas, and in the sarcoma-mesothelioma area. Simulated prototypical trials involving an aggressive and an indolent cancer were examined to evaluate the precision with which treatment differences would be measured when pathologically ineligible cases were included. Analysis of these models indicated that in trials in which the pathology exclusion rate is greater than 10%, slide review is prudent. When the exclusion rate is 5% to 10%, the necessity for pathology confirmation depends on the scientific objective of the trial. If less than 5% pathology exclusions characterize a clinical trial, routine pathology review is not justified. Routine histopathologic review for quality assurance in cooperative groups is not always necessary and may be eliminated in studies of the more common cancers. The practical value of reallocating limited pathology resources for investigative studies in cooperative groups is significant.

Symposium on methodology and quality assurance in cancer clinical trials: Cancer treatment reports, number 10, 1039–1233

Statistics in MedicineVolume 6, Issue 2 p. 213-213 Book Review Symposium on methodology and quality assurance in cancer clinical trials: Cancer treatment reports, number 10, 1039–1233 J. Houghton, J. Houghton CRC Clinical Trials Centre King's College School of Medicine and Dentistry, London U.K.Search for more papers by this authorR. A'Hern, R. A'Hern CRC Clinical Trials Centre King's College School of Medicine and Dentistry, London U.K.Search for more papers by this author J. Houghton, J. Houghton CRC Clinical Trials Centre King's College School of Medicine and Dentistry, London U.K.Search for more papers by this authorR. A'Hern, R. A'Hern CRC Clinical Trials Centre King's College School of Medicine and Dentistry, London U.K.Search for more papers by this author First published: March 1987 https://doi.org/10.1002/sim.4780060216AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume6, Issue2March 1987Pages 213-213 RelatedInformation

Forms control and error detection procedures used at the coordinating center of the Multiple Risk Factor Intervention Trial (MRFIT)

Although methods used for data collection and quality assurance for large-scale clinical trials are important to critical reading of trial results and have been published, such reporting is the exception rather than the rule. In the MRFIT, systematic methods for processing large volumes of data over a long period of time were developed. The methods were designed to detect and control a variety of errors and to leave a complete audit trial of the processing of forms and corrections to forms. Many of these methods evolved and were refined during the course of the study as a result of trial and error. If one were to start over, the methods described herein would be modified. The field of data processing is evolving, and it is important for statistical and data processing staff of coordinating centers to recognize this and continually evaluate and update their methods. For example, the simultaneous entry and computer editing of forms is becoming more feasible with time. Also, more sophisticated intelligent data entry equipment is available for central use. Near the end of MRFIT, some data received at the Coordinating Center were entered and edited on a minicomputer. The parameter-driven edits described previously were performed at the time of data entry. Additional modifications to the content of the data dictionary for future studies are also being considered. The incorporation into the data dictionary of consistency checks (both deterministic and probabilistic) between fields on different forms would facilitate the specification of complex edit checks and would provide better documentation of the edit checks actually performed. Incorporating definitions of the numeric codes for each field would improve the documentation and facilitate reporting using statistical packages. Dedicated computer hardware should also be a major consideration of coordinating centers in future clinical trials. For MRFIT, a dedicated system was used from 1978 to the end of the trial. With the continued decline in hardware costs, dedicated systems can and should be considered, even for trials much smaller than MRFIT. We believe the system developed for processing data in the MRFIT has several advantages. It satisfies the requirements identified by Karrison or a system of data editing and control, it is largely self-documenting as a result of the data dictionary approach taken, and it is easily adaptable to other clinical studies.

Symposium on Methodology and Quality Assurance in Cancer Clinical Trials

Symposium on Methodology and Quality Assurance in Cancer Clinical Trials

Radiotherapy quality assurance in clinical trials

The goal of radiation therapy is to yield the greatest possible uncomplicated local and regional tumor control. An acceptable quality of life with few severe complications, anatomical defects or psychological disturbances should be an integral objective of excellent radiation therapy. Inasmuch as higher doses of irradiation and adequacy of treatment portals (volume irradiated) appear to correlate with greater probability of tumor control and major complications, there is a critical need to optimize treatment planning and quality assurance in radiation therapy. Along with this, techniques must be developed for reliable patient reposition and immobilization so that the optimized treatment plan can be translated into precise delivery of the irradiation. It is obvious that in clinical trials the basic parameters of therapy need to be optimally observed, in order to make comparison of experimental arms more reliable. It is easier to achieve uniformity of technical factors in a study at a single institution than in multi-institutional cooperative groups. Thus, stringent criteria must be incorporated into the protocol describing the requirements and techniques for planning and delivery of the radiation therapy. Furthermore, the dosimetry checks carried out by the Radiological Physics Center should be an integral part of this program. In some studies it is necessary to do an initial review of dosimetry factors and portal films. This alerts the radiation oncologist to variations from the protocol and, with prompt feedback and correction of the potential error, will ensure the complete evaluability of the case. Since an increasing number of reports point out that the doses of irradiation delivered and the volume treated may affect therapeutic results, a completed case review should always be carried out. Some cooperative group studies strongly suggest a correlation between the compliance with the protocol and the results of the trial. Costs of these programs in clinical trials should be justified since, for a small investment, the evaluability rate in a protocol can be increased by 10%. The increase of patient evaluability significantly decreases the cost per evaluable patient. Furthermore, the reliability of the data of the trial will be greatly enhanced by a strong quality assurance program.

Clinical trial management, quality assurance and sufficiency of data.

Clinical trial management, quality assurance and sufficiency of data.