Reporting clinical research

Several U.S. researchers speculate that the authors of the French report mistakenly drew their conclusion from published studies analyzing naturally occurring creatine found in protein-rich animal products such as beef and pork. When these creatine-containing foods are heated and cooked, the creatine and amino acids interact to form compounds known as heterocyclic amines (HCAs), which have been shown to cause cancer in animal studies. The level of HCAs can vary with cooking method and other factors. Creatine monohydrate does not contain HCAs, and as of early 2002, no published or reported clinical research existed to demonstrate that creatine monohydrate taken in supplement form causes cancer. 

Few people come to the pharmaceutical industry from academia and health-related positions with the requisite knowledge and skills necessary to plan, conduct and report clinical research to regulatory authority standards. This knowledge and skill usually need to be provided by sponsors to all levels of new staff by the way of in-house training. 

The following is a description of the typical knowledge and competencies needed to plan, conduct and report clinical research in a regulated environment. Each competency is described along with the knowledge and skills a sponsor s representative would need to be successful in completing the task. 

Competencies associated with reporting clinical research... 

Competencies Associated with Reporting Clinical Research... 

The editor would like to thank the participants, all of whom provided timely and complete reports in their areas of expertise, and Dr. J. Michael Walsh (Division of Clinical Research) and Nicholas J. Kozel (Division of Epidemiology and Statistical. Analysis) who cochaired the Technical Review. Special thanks go to Dr. R. Stanley Burns, who made a major contribution by suggesting suitable clinical investigators. 

The data and information about an individual drug developed through Phase I, II, and III studies are extremely important to the medical community. For many drugs Phase I, II, and III data may be all, or nearly all, that is available about the clinical use of the drug at the time the product is marketed. During the time the product is in Phase I, Phase II, and Phase III, some of the compound s product and clinical data may be presented at professional meetings, published in preliminary reports, or otherwise made available to the scientific and business communities. However, it is not uncommon for a drug to be approved by FDA without the presence of its clinical research in the published biomedical literature. 

Bugeja G, Kumar A, Banerjee AK (1997) Exclusion of elderly people from clinical research a descriptive study of published reports. BMJ 315(7115) 1059... 

Clinical research coordinators (CRCs) are the research personnel who assist with pahent visits, and perform study-related procedures that do not require a physician (phlebotomy, vital signs, adverse event, and concomitant medicahon discussions, etc.). CRCs provide the PI or physician with data required for interpretation, medical decisions (inclusion/exclusion, dosage adjustment, patient withdrawal, adverse event causality, etc.), and trial oversight. In addition, CRCs are usually responsible for transcribing source documentation (medical records, clinic notes, laboratory reports, etc.) into case report forms (CRF) supplied by the study sponsor. 

Fred Sidell had done an heroie job during my absenee. Under his leadership, Clinical Research was publishing more researeh papers than any of the other three Medical Laboratory departments. Most reports were classified, but it was encouraging that some had been approved for open pubheation in mainstream... 

Researchers responded to this assignment promptly and vigorously, finishing their report in less than a year. Fred Sidell told me that a truck from Washington DC came empty and left loaded to the gunnels with multiple copies of everything in the Clinical Research Department document library, plus an unknown amount of material from other files. 

As soon as fraud is suspected, a series of steps needs to be followed which have been thought out and written down as an SOP before any clinical research commenced. Where possible, additional evidence should be obtained, usually by the use of a competent QA auditor. In the meantime, only the minimum key individuals should be made aware of the problem until sufficient evidence has been obtained to establish the truth. The appropriate authorities such as the national drug industry organisation and the regulatory authorities should be informed if fraud has taken place. Sometimes, other sponsors will have reported additional evidence that fraud is taking place at a particular site. The site will need to be closed if study subjects are still being recruited and a full explanation provided to the authorities. Any clinical data collected will need to be reviewed and a decision made as to whether any of the data can be included in an analysis. To a pharmaceutical physician, fraud is never an easy situation. It usually involves a professional colleague and there is always the worry that the established facts have been misinterpreted. However, a fraudulent individual cannot be tolerated in modern clinical research. 

This second assumption is equivalent to an assumption that there is no regression-to-the-mean. Regression-to-the-mean is a phenomenon originally reported in 1885 by Galton who showed that the children of tall parents tend to be shorter than their parents, and conversely children of shorter parents tend to be taller than their parents. This is of importance in the context of clinical research because patients are chosen to participate in a clinical trial because they have... 

Clearly, therefore, those involved in drug safety monitoring need to liase closely with both clinical research and medical information scientists. In addition, those responsible for clinical drug safety must undertake periodic safety update reports (PSURs) at predetermined intervals, in accordance with current International Conference on Harmonisation (ICH) guidelines. Such routine analyses can identify new safety signals as soon as they become detectable. 

Table 5-27 and Table 5-28 summarize the clinically relevant pharmacokinetic and pharmacodynamic properties of other novel antipsychotics ( 326). Drug interactions with these agents were not systematically evaluated because controlled clinical trials usually prohibit concurrent medications. There are also many special circumstances (e.g., patients with comorbid medical diseases, substance abuse, epilepsy, or atypical indications such as agitation associated with mental retardation or dementia) that are not usually addressed in clinical research trials. Thus, much remains to be learned about significant drug interactions in these patient groups. To our knowledge, however, no consistent, serious, clinically relevant interactions have been reported. 

In the quarter of a century since Kohler and Milstein s ground-breaking work, more than 100,000 MABs have been reported. Many researchers were quick to recognize the therapeutic potential of MABs and from the late 1970s academic and commercial laboratories rushed to produce MABs specific for a range of human diseases. This initial optimism was soon suppressed as clinical trials began to show that mouse... 

There have been numerous clinical studies examining the analgesic effects of TCAs in chronic pain, and the review of these is beyond the scope of this chapter. There are a number of reviews covering these studies (e.g. Onghena and van Houdenhove, 1992 McQuay et al., 1996 Feuerstein, 1997). In contrast, the effects of TCAs in acute pain have not received much attention in clinical research. There are only a few controlled studies with mixed results, reporting no effect of desipramine or amitryptiline on postoperative dental pain when given alone but enhanced... 

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