Conduct of study

Eactors ki the design and conduct of studies have been pubUshed (72—74). 

The conduct of studies of medical devices in the US that have not been cleared/ approved by the FDA is regulated via Investigational Device Exemption (IDE) regulations set out in 21 CFR Part 812. Considering the type of device and the level of associated risk involved, investigations maybe conducted as IDE-exempted studies. Abbreviated requirement studies, or studies subject to full IDE requirements. 

It should be kept in mind that there are a number of common mistakes (in both the design and conduct of studies and in how information from studies is used) that have led to unfortunate results, ranging from losses in time and money and the discarding of perfectly good potential products to serious threats to people s health. Such outcomes are indeed the great disasters in product safety assessment, especially since many of them are avoidable if attention is paid to a few basic principles. 

The actual requirements of the November 8, 2000 ICH guidelines are broadly outlined. They call for the conduct of studies in a core battery to assess effects on the cardiovascular (Table 19.1), respiratory (Table 19.2), central nervous system (Table 19.3) and secondary organ system (Table 19.4) effects. Follow-up studies for the care battery are also required on a case-by-case basis for the three main organ systems. 

Provision of adequate competent medical staff is essential for the safe and ethical conduct of studies in humans. Decisions about whether a volunteer fulfils the entry criteria for a healthy subject or should be withdrawn from a study, how to respond to an unexpected adverse event and when to discontinue a study can prove challenging to the most experienced physician. Similarly, research nurses need many organisational and other skills over and above those that they acquired during their basic clinical training. Scientific staff must be competent in the techniques that will provide the essential data. All must be properly briefed about what will be required of them during the course of a study, and must be fully familiar with local standard operating procedures (SOPs) in compliance with good clinical practice (GCP). 

One approach would have been to continue the program of for-cause inspections, but they would be triggered only by perceived deficiencies in the data after submission to the agency, and thus would not have provided systematic assurance that all studies were valid or guidance to laboratories on standards for conduct of studies. 

The proposed regulations went beyond these basic requirements for a valid study by requiring each study to have a study director who would have ultimate responsibility for implementation of the protocol and conduct of the study [ 3e/31(a)], and each testing facility to have a quality assurance unit to monitor conduct of studies. The concept of a quality assurance unit to monitor study conduct was a new one to most laboratories but a familiar one in manufacturing facilities operating under various GMP regulations. 

If a testing facility is too small to handle the volume of work it has set out to do, there may be an inclination to mix incompatible functions. Examples might include the simultaneous conduct of studies with incompatible species (e.g., old world primates and new world primates) in the same room, setting up a small office in the corner of an animal housing area, housing an excessive number of animals in a room, or storing article/carrier mixtures in an animal room. 

Kauffman RE, Banner W Jr, Berlin CM Jr, et al. Guidelines for the ethical conduct of studies to evaluate drugs in pediatric populations. Pediatrics 1995 95 169-177. 

As previously indicated, these GLP regulations and international guidelines were written to address the issue of the conduct of studies and assuring their quality. In order to address these issues, each of the regulations and the international guidelines calls for the establishment of a Quality Assurance Unit or "quality assurance function" within each laboratory. They also specify that certain tasks be carried out by this unit or function. These requirements have resulted in the creation of a new scientific, managerial professional - the quality assurance unit... 

Each testing facility shall be of suitable size and construction to facilitate the proper conduct of studies. Testing facilities which are not located within an indoor controlled environment shall be of suitable location to facilitate the proper conduct of studies. Testing facilities shall be designed so that there is a degree of separation that will prevent any function or activity from having an adverse effect on the study. 

The programs for assuring GLP compliance have already been described above in Sections 36.4 and 36.5. In summary, the European Union guided by OECD requires registration of all facilities claiming conduct of studies under GLP in a program for GLP compliance.The identified laboratories are inspected... 

OECD (1997). Guidance Document for the Conduct of Studies of Occupational Exposure to Pesticides During Agricultural Application, OECD Environmental Health and Safety Publications, Series on Testing and Assessment No. 9, OECD/GD(97)148, Organization for Economic Co-operation and Development, Paris, France. 

Selecting qualified persons to monitor the conduct of studies. 

Guidance Document for the Conduct of Studies of Occupational Exposure to Pesticides during Agricultural Application (1996). 

The Study Director who must have appropriate training and experience, has overall responsibility for conduction of study, assures that protocols are followed, and is solely responsible for authorizing changes in protocols. 

In addition, the ICH issued the Ell Pediatric guideline on Federal Register 2000. This outlines conduct of studies in children and is utilized by many countries. This guideline also addresses availability of formulations and labeling for children. 

At the time of writing, the conduct of studies in non-patient volunteers in the UK is not regulated by the Medicines Act (1968). Similarly, studies in non-patient volunteers in the Netherlands, Belgium and some other European countries do not require regulatory approval. This situation is about to change, as the EU Directive issued in 2001 will require to be implemented in all European countries by 2004. All healthy volunteer studies will then require regulatory approval in addition to that of an ethics committee. The Directive, with which all member states must comply, makes no distinction between healthy volunteer studies and clinical trials in patients who may benefit from treatment. However, the precise details of documentation required for authorisation of healthy volunteer studies may vary from country to country it is possible that the application in the UK will be somewhat less detailed than the current Clinical Trials Exemption. 

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