Therapeutic Innovation & Regulatory Science

Great progress has been made in clinical data processing technology since computers were first used in the late 1950s. Substantial progress has been made in collection, processing, display and analysis. Making an historical record of this rapid progress would be an important contribution to our understanding the nature of technological progress. Despite the great technical advances in clinical data processing, these advances have not resulted in a significant shortening of the drug development process. The major challenges of the coming decade are in efficient remote data entry, implementation of the worldwide marketing authorization application, direct transmission of data to agencies, and the extension of clinical investigation of data processing technology to post-marketing surveillance.

Prompted by a host of pressures challenging the timeliness of the FDA's process for reviewing pharmaceutical products for marketing approval, the Center for Drugs and Biologics, in cooperation with volunteering pharmaceutical firms and industry support organizations, is investigating the feasibility of several different activities aimed at finding optimizations for its review methodology. This article will describe several of these different activities, discussing methodologies proposed and various preliminary expectations. For those pilot activities already in progress, some experiences already gained will be shared. For activities not yet begun, some comments regarding structure and expectations will be stated. Other ideas for future efforts, where there may be potential benefits for both the government and for industry, will be provided.

We undertook a comprehensive retrospective analysis of already-approved drugs to assess the likely impact of the Drug Price Competition and Patent Term Restoration Act on market exclusivity of future new drugs. We analyzed data for new drugs approved between 1962 and 1984 and applied the new law's exclusivity and patent restoration formulas to each drug. Our simulation suggests that new drugs approved in the first years following enactment will gain 2 to 3 years of additional product protection, while those approved later will gain 3 to 4 years of product protection. In either case, the effective patent life will be considerably less than the 17-year statutory patent period. The full impact of the law will not be known for at least a decade, but study and analysis should begin now.

A validation plan is developed to show beyond any doubt that a computer program, software system, or hardware configuration will consistently perform as intended within pre-established operational limits. This concept, while stating fact, is defensible with the implementation of a comprehensive, well-documented validation plan. It has been widely stated and published by P. J. Motise¹ of the Food and Drug Administration that there are five main areas of system validation:

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Defining the task to be performed and matching the task to a computer system.

This paper will identify an approach the author has implemented at Revlon Health Care R&D to satisfy FDA validation requirements.

At Hässle, we have created a computing environment that is unusual in two major aspects: (a) It is extremely distributed, yet does not rely on personal computers; and (b) it has a very high degree of user interaction and acceptance. The tools to create this environment in the forms of machines, software, and organization are discussed.

A graphics storage and retrieval system for chemical structures has recently been implemented on an IBM 3083 under an MVS/XA TSO operating system. This article describes the past history of the Schering-Plough Technical Documentation Information Center as it relates to storage and retrieval of chemical structures, the reason for and the selection of a graphics display system, its implementation and interface with Schering's Biological Database System, and the future direction of this new project.

Objectives of the Burroughs Wellcome Company's Product Information Section include locating, organizing, processing, storing, retrieving, and disseminating published information on the company's investigational and marketed products. Literature is collected from a wide range of international resources and integrated into a computerized INQUIRE^® database called PRODBIB. PRODBIB contains bibliographic information and detailed subject indexing for over 58,000 papers. The file is utilized for answering inquiries and for generating bibliographies in support of Investigational New Drug (IND), New Drug Application (NDA), and other submissions to the FDA. In January 1982 a joint project was undertaken with the Product Surveillance and Epidemiology Department to add meaningful data from the literature to the “Adverse Reaction Reporting System,” which is a separate INQUIRE database originally designed for unpublished reports. The integration of published adverse drug experiences into this system has provided us with a unique foundation for post-marketing surveillance and systems for monitoring adverse reactions are of special interest in light of the NDA rewrite.

Medline is a computerized indexing and abstracting service for biomedical literature and is one of the most commonly used methods of literature retrieval. An alternative manual technique is fan searching. Fan searching involves scanning bibliographies of relevant articles from online Medline searches of the most current literature. We compared the amount of relevant literature retrieval between these two methods. We conducted 14 searches, which were randomly selected from typical drug information questions answered in our center. Overall only 20% of the references from computerized offsearches were identified by manual fan searching. In only one instance did fan searching identify greater than 50% of the same citations listed in the offsearch. We conclude that fan searching is not a comprehensive method of literature retrieval.

The objective of this study was to examine the role of the community pharmacist in providing medication and health information. The number and types of questions received, the references used in answering clinical questions, and the appropriateness of those responses were determined. A total of 1,133 questions was recorded. From observational data, it was determined that 78% of the questions were administrative and 22% were clinical. Product recommendation questions were the most common clinical questions followed by dosage, indication, and interaction questions. Although references were not used frequently, manufacturer's information was the most common type used. Pharmacists' responses to clinical questions were evaluated by an expert panel on three components of appropriateness with mean scores of 2.7 for accuracy, 2.5 for completeness, and 2.7 for utility (3 = maximum score). Possible reasons for underutilization of the pharmacist as an information source to patients and health professionals are discussed along with recommendations for improvements.

Drug information resources were observed in 50 community pharmacies in a large midwestern metropolitan city. References found in chain and independently owned pharmacies were compared. A complete set of current required references, as defined by state law, was found in 32% (8/25) of the chain pharmacies and 64% (16) of the independent pharmacies, (p = 0.0475). Of the required sources observed in this study, drug interaction texts were found most frequently and poisoning/toxicology references were cited the least. The independent pharmacies maintained a wider variety of references compared to the chain stores (18 v 14). The majority of journals observed in the community setting were management oriented and only three independent pharmacies maintained major biomedical journals. Pharmacists in both chain and independent settings should further develop their libraries in order to maximize their role as drug information providers.

A distributed data processing system was developed and implemented in the Systolic Hypertension in the Elderly Program (SHEP) pilot study, a multicenter randomized double-blind clinical trial. The SHEP system was based on minicomputer hardware and database management software that was extensively customized for our application. The system provided on-site data entry, editing, and retrieval at each of five clinical sites, and permitted local randomization of the study participants upon confirming eligibility. The system included protocol guidance and monitoring functions to assist clinicians in administering the complex, stepped-care treatment protocol. Finally, the system provided a communication network for messages and documents, as well as data, which has many advantages in a study involving multiple centers in various locations. Dispersing much of the data processing to the clinics in SHEP increased the access to and responsibility for the data at the clinic level, while simultaneously facilitating coordinating center monitoring and control of protocol administration. Distributed systems pose some special technical challenges, but have many advantages for use in collaborative studies.

In the last two to three decades, Saudi Arabia has experienced rapid and radical changes in all fields, including the health field. This rapid change is due to an increase in oil revenue. This article concentrates on drug regulation and serves as a vehicle to provide information on drug distribution, utilization, and the regulations for importing and ensuring the safety and efficacy of drugs in Saudi Arabia. The organizations that provide health services free of charge are also listed. These changes have and will provide a better future for the citizens of Saudi Arabia by bringing about improved health care and access to therapeutics accounts.

The publication of the results of clinical trials is important to the health care community, to investigators conducting research, and to companies that manufacture pharmaceutical products. At Norwich Eaton Pharmaceuticals, Inc, technical writers help to prepare manuscripts reporting the results of clinical trials. The writers identify the journal most suitable for the paper and evaluate the focus, style, and editorial requirements for that journal. They then tailor internal reports or preliminary drafts prepared by the clinical investigator into manuscripts suitable for submission to the target journal. They determine what information is missing, superfluous, or inappropriate and coordinate the necessary additions, deletions, and revisions. Writers seek advice from experts in the areas of information science, statistics, medicine, marketing, sales, and law during manuscript preparation. This paper describes the nature of the information sought from individuals in other disciplines and illustrates how each manuscript is the result of a team approach.

There has been intense activity during the past 2 years in exploring the applications of personal or microcomputers (PCs) as a means of capturing data emanating from clinical investigations. A number of pharmaceutical companies, including Ives Laboratories, have explored this method. Conceptually, this idea is very appealing. Properly posed to management or the medical monitor, the presenter can argue that this method of capturing data is the most effective (both in cost and time) and superior to other currently available procedures. However, detailed examination of this technology reveals that before this method of data collection can be accepted as viable and effective, especially on a large scale, a number of issues must be resolved. The purpose of this paper is to examine these issues, especially in the context of clinical research as sponsored by the pharmaceutical industry. An alternative approach to remote data entry, utilizing the currently available facsimile transceiver technology, is discussed.

The storage, retrieval, and dissemination of information constitutes a major function of any drug information service (DIS). We developed a computerized system for the storage and retrieval of data from drug information requests (DIR) using a MUMPS-based information system. In the past, DIR forms were stored in looseleaf binders and filed chronologically. Due to the success and increased use of our DIS, this manual filing system became inadequate and awkward to use. Our solution was to develop a computer system where data could be entered from DIR forms and retrieved rapidly and easily. Each DIR was reviewed and key data elements were selected for input. The DIS files may now be searched online rapidly and efficiently. The MUMPS-based information system has provided open access for all staff pharmacists, 24 hours a day. The benefits have been an increase in both the quantity and quality of drug information provided.