Clinical verification

In vitro or in vivo verification of Clinical verification of inteiindividual ... 

Many clinical laboratories find it necessary to develop methods to detect various infectious agents for which there are no commercially available methods or systems. Laboratory-developed tests (LDT), formerly known as home-brew assays or in-house developed assays, are those assays tliat have been fuUy developed and validated by the laboratory that offers the testing. Usually, these assays use a combination of reagents that are purchased separately from various manufacturers. The analytical and clinical verification of the LDT is the responsibility of each laboratory, and this verification procedure is more complex than verification of an FDA-cleared or FDA-approved test. 

Verification of a test is a complex process that can be divided in two phases analytical and clinical verification. Analytical verification provides critical information about the performance of the test, while chnical verification establishes the clinical indications for the test. Determination of the clini-... 

The proposed indications for use of the test should be defined before starting the clinical verification. As for any tests (see Chapter 13) the indication for use of an assay could involve the making of a diagnosis, the ruling out of a diagnosis, the provision of prognostic information, or the monitoring of disease—especially, in infectious diseases. 

According to the provisions for an NDA, clinical studies on a new medicinal product in China are classified into two categories clinical trials and clinical verification. 

Clinical trials on new medicinal products in class 1, 2 or 3 are required to be approved by the central Bureau (see Table 52.2). Clinical verifications, mainly for products in classes 4 and 5, may be approved by a local Health Bureau. 

Since the introduction of Tc-l,l-EC as a tubular radiotracer (Verbruggen et al. 1992), clinical verification of the pharmacokinetic parameters has been obtained in normal controls (Van Nerom et al. 1993) and in patients (Gupta et al. 1995 Kabasakal et al. 1995), using standard procedures and also by comparison with the reference compounds orilio-iodohippurate (OlH) labeled with iodine-125 and with " Tc-mercapto-acetyltriglycine (MAG3) (Kabasakal et al. 1995 Ozker et al. 1994 Stoffel et al. 1996). Tc-EG complex showed high similarity with OIH with respect to plasma clearance and elimination half-times (Ozker et al. 1994 Van Nerom et al. 1993). " Tc-EC was... 

The successful clinical use of titanium and cobalt-chromium alloy combinations has been reported Lucas etal. also investigated this combination using electrochemical studies based on mixed potential and protection potential theories. Verification of these studies was made by direct coupling experiments. The electrochemical studies predicted coupled corrosion potentials of -0.22 V and low coupled corrosion rates of 0.02 ft A/cm. Direct coupling experiments verified these results. The cobalt-titanium interfaces on the implants were macroscopically examined and no instances of extensive corrosion were found. Overall, the in-vitro corrosion studies and the examination of retrieved prostheses predicted no exaggerated in-vivo corrosion due to the coupling of these cobalt and titanium alloys. 

All clinical trial information should be recorded, handled, and stored in a way that allows its accurate reporting, interpretation and verification... 

There are hidden gold mines under our noses—in house data becomes the new lamps for old on the tons of old clinical data from 50 years of R D— but of course, none of it is electronically accessible. It is called a library Many organizations have undertaken huge OCR (optical character recognition) projects to scan laboratory notebooks—some data even exists on microfilm and microfiche. As it is a legal requirement for a drug submission to provide provenance of scanned notebooks [38], paper, and microfilm, many businesses concentrate solely on the capture and verification of this data, rather than considering it a valuable resource to be remined. 

Approximately one-third of patients with MDD do not respond satisfactorily to their first antidepressant medication.37 In such cases, the clinician must evaluate the adequacy of antidepressant therapy, including dosage, duration, and patient compliance.17 Treatment reappraisal also should include verification of the patient s diagnosis and reconsideration of clinical factors that could be impeding successful therapy, such as concurrent medical conditions (e.g., thyroid disorder), comorbid psychiatric conditions (e.g., alcohol abuse), and psychosocial issues (e.g., marital stress).16... 

AU the medical records of the subject should be available for comparison with the data recorded in the case report form (CRF). In the past, physicians have not allowed medical records to be available for the so-called source verification by non-physicians since they felt that this broke the strict confidentiality of the study subject s medical records. However, frequent mistakes in transferring important clinical data to the CRF, the recruitment of subjects who do not meet the inclusion and exclusion criteria and the occasional blatant fraud has led to an insistence by sponsors and regulatory agencies for sponsor s review of study documentation. Indeed, verification of source data cannot take place without access to the medical records of the study subject by the sponsor s staff. 

Inspectors will visit the investigator site and may possibly wish to visit the sponsor s office. They will review the documentation of the study file (see Box 7.1). Approval documents of the lEC will be compared with any amendments made to the protocol or to the subject s information sheet/ICR Consent forms for the study subjects will be inspected to establish who actually gave consent and whether this was before entry into the clinical study. A thorough source data verification of the CRF with the source documents, including the medical records, will be undertaken. Documentation relating to drug accormtability wiU be matched with each subject s CRF The facilities wiU be reviewed and the site staff interviewed. Further information can be obtained from... 

The primary consideration of a clinical investigation of a device is assessment verification of the manufacturer s claims for the technical performance of the device. Safety considerations are, nevertheless, relevant in that the clinical investigation should determine and assess any undesirable adverse effects, but the main thrust of the clinical evaluation, and in particular of the conformity assessment by a notified body or the manufacturer to permit marketing, is on technical performance rather than a complete evaluation of safety. It is an essential requirement for marketed devices that [A]ny undesirable side-effect must constitute an acceptable risk when weighed against the performances intended. ... 

Monitor means one or more persons appointed by the Sponsor to monitor compliance of the Clinical Trial with ICH GCP and to conduct source data verification. 

The verification of compliance with the standards of good clinical practice and the need to subject data, information and documents to inspection in order to confirm that they have been properly generated, recorded and reported are essential in order to justify the involvement of human subjects in clinical trials. 

Verification of compliance of investigational medicinal products with good clinical and manufacturing practice... 

One of the main requirements is the verification of the biocompatibility and a risk management, which have to consider the results of a clinical study and post-marketing (vigilance) studies [17]. 

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