Among health professionals laboratory tests are called in vitro diagnostic (or IVD) tests because they were traditionally performed in a test tube (in vitro means literally "in glass") and because they are mostly used to help determine (or diagnose) what is wrong with a patient. In vitro is also used in contrast to in vivo, which means "in life" . Unlike many other medical diagnostic procedures which physically effect the patient, in vitro tests are performed on samples and do not come into contact with patients. For this reason in vitro diagnostics are generally considered to have a much smaller risk for patients than other medical devices.

Valuable information about the way the body is functioning and the state of health can be obtained by taking samples (for example blood, tissues or urine) from the body and performing IVDs on these samples in a medical laboratory. The tests performed include microscopic examination of cells and structures, measuring the concentrations of various chemical and biochemical components using automated analysers, counting cells, measuring physical properties and making biological cultures. Most medical laboratory tests are made in connection with an infection, an accident or to follow the treatment that is given.

One of the first steps after a medical examination is often to take a blood sample and to request the medical laboratory to carry out a number of physical and biochemical tests. The results of the tests are used in disease management to assist the doctor (in the hospital or in general practice) in making the best decisions about treatment. Laboratory tests are also widely used in prevention of disease, for example, to screen populations or groups for hidden disease or risk factors and are being used increasingly in health management to check personal health status. The results of these tests are a unique source of objective information about the person's state of health or disease.

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The industry produces analytical instruments and the reagents and accessories which are used to do in vitro diagnostic tests. Reagents are highly specific biological or chemical substances in special solutions that are able to combine with target substances in the samples and give a product that can be measured or seen. The analytical instruments are the various machines and equipment that are used to bring samples and reagents together or to measure other parameters in the samples.

The in vitro diagnostics industry also produces a number of accessory products like software programs to run the instruments, control solutions to check the performance of the systems in addition to supplying information and training for users. Together the reagents, the instruments and the accessories are referred to as in vitro diagnostic "systems".

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Most people are aware of pregnancy tests available in high-street pharmacists, and many are aware of the blood glucose monitors used by people with diabetes to help manage their therapy.

The IVD Industry is developing many more tests in designs specifically for home use, such as those used to monitor coagulation therapy, or to screen for various forms of cancer. Products to help pinpoint a woman's most fertile stage in her menstrual cycle, to screen for the biochemical markers associated with osteoporosis, and simple tests for urinary tract infection are amongst those arriving on the pharmacists' shelves.

Although all self-testing products have extensive information in the packaging explaining their use, the pharmacist will also be willing to discuss any questions about them that the consumer might have.

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The role of the In Vitro Diagnostics Industry

Traditional Values

In vitro diagnostic testing has traditionally been positioned in a clinical support role, as an aid to the physician's final diagnosis. While this utilisation is clearly appropriate, it also means that the ability of laboratories and IVD manufacturers to contribute optimally to the healthcare system depends to a very large degree on the physician's knowledge and behaviour. Often, however, clinicians have not kept up with the rapid pace of innovation and development in IVD technology which has led to a large repertoire of highly sensitive and specific tests. This fact has undermined the ability to maximise testing utility and the opportunity to reduce morbidity and downstream healthcare costs. Whilst the majority of healthcare professionals and management concentrate on the daily task of moving the ever expanding waiting list of patients requiring treatment through the limited resources available, there is growing interest in the use of diagnostics to predict or detect at an early stage many conditions which, if treated at their outset, can avoid the need for more costly interventions at a later date, and thus shorten the queue from the other end.

Study shows poor awareness of IVDs

The Clinicians' general lack of awareness of IVDs was recently confirmed in a study conducted in the United Kingdom by Watson Biomedical on behalf of a forum of professional and industry associations lead by the British In Vitro Diagnostics Association (BIVDA). BIVDA exists as a trade association for the industry dedicated to the development, manufacture and supply of IVDs in the UK, and in conjunction with the Department of Trade and Industry is carrying out a project designed to improve the competitiveness of the industry. In addition, BIVDA represents British interests in Europe in the area of legislation and market awareness. This latest study was aimed at hospital and general practitioners, the pathology professions and healthcare management. In response to a question regarding the factors that would increase their overall use of diagnostic testing, about half of the physicians surveyed cited needs for a wider range of tests, increased test accuracy, more definitive tests and more information regarding the availability of tests. This, however, was in the context of very limited awareness of the advances the diagnostic industry has achieved over the past decade.

Short term financial pressures

In addition to the limitations in physicians' knowledge concerning the optimal use of IVD tests, physician behaviour is increasingly being shaped by financial pressures, whether exerted by hospital administrators or by managed care organisations. While in years past, physicians might have felt remiss in their treatment of a patient if they failed to order vast profiles made up of the IVD tests available at the time that might assist them in arriving at a differential diagnosis or in possibly unearthing a hidden condition, current thinking encourages a more discriminating approach to IVD testing, but unhappily in a climate of limited awareness of the tools available.

Another recently published survey reveals the possible consequences of increased efficiency in the use of clinical laboratory services. Over a period of seven years (1985 to 1991), the IVD test-ordering practices of eighty-five general practitioners in the town of Maastricht (Netherlands) were monitored by the laboratories receiving the requests. The laboratories were asked to provide constructive feedback to each physician regarding his or her ordering patterns and the appropriateness of each request. The effect on testing volume was considerable. Over the seven-year period of the study, the number of tests requested (which were tracked for each of four clinical disciplines), declined by up to sixty percent. This period also marked a change in technology in analytical instrumentation, the multichannel profiling machines delivering up to twenty-three simple tests giving way to selective analysers and the growth in availability of immunoassays for thyroid, fertility and other hormones, cancer markers, cardiac markers, infectious diseases, specific proteins, and therapeutic drugs. Financial pressures and the rationalisation of testing procedures coincided with an increasing availability of more and more highly specific diagnostic assays.

The argument for reversing the trend

Because it was easy to measure and therefore easy to cut, the pathology laboratory workload has become a favourite target for budgetary reductions. There is now, however, a growing recognition in the healthcare community that IVD testing now accounts for only a small fraction (about one percent) of total health care expenditures, and that further cuts in this area might result in a net increase in overall health care costs due to missed diagnoses and over or under medication due to inadequate monitoring of therapeutic drugs. Indeed this is a new paradigm that may provide the IVD industry with the opportunity to assume its rightful place as an equal partner with the therapeutic side of health care delivery. The new model recognises that relatively small IVD expenditures can lead to significant net savings for the health care system.
It is a major part of BIVDA's remit to explore the evidence to support this position. Whether it is testing for infections such as Helicobacter pylori, responsible for hundreds of thousands of cases of chronic dyspepsia, or the utilisation of tests for the cardiac specific Troponin assays in the differentiation of the causes of acute chest pain, to cite just two examples, the use of IVDs can deliver significant downstream savings in the health care budget and in the quality of life of the individuals concerned. It has been argued that the use of IVDs to detect the early stages of late-onset (type 2) diabetes as an alternative to allowing the onset of the serious sequelae of the condition to bring the situation to the attention of the practitioner would help reduce the overall costs of the disease, some five percent of the total healthcare budget. This in addition, of course, to the benefits brought to the sufferer in terms of quality of life and personal performance at work and at leisure. It is estimated that, in the UK alone, some one million individuals are diabetic, but undiagnosed, all of which will in time succumb to the expensive and unpleasant complications of uncontrolled glycosylation, and further swell the waiting lists.

One important component of health management

The in vitro test is, of course, only one component of the total clinical investigative procedure. Physicians retain ultimate discretion in assigning a disease state to each patient based upon a mix of clinical and laboratory findings. In many instances, however, the balance of that mix leans strongly towards laboratory findings. Moreover, the IVD test has a number of roles within the overall patient management programme, including screening, diagnosis, therapeutic monitoring, compatibility testing and post-surgical monitoring. The leading diagnostic company in the world invests one million dollars a day in research and development, in parallel hundreds of small biotech companies, many working in conjunction with universities, carry out research projects related specifically to diagnostic tools and new technologies. The challenge is to provide information concerning the fruits of this work to the medical practitioner faced with a deluge of material detailing advances across the whole spectrum of medicine and pharmaceuticals. In addition, the positive financial outcomes of the use of these new tools need to be brought to the attention of doctors, health administrators and politicians alike.

The challenge

Diagnostics clearly have the potential to evolve into a wholly integrated component of the health care mix. More self-administered diagnostics will follow the pregnancy test onto the shelves of the pharmacist and the supermarket. Rapid technological advancement in such areas as vascular disease markers, tumour markers, DNA probes for infectious diseases, genetic testing and pharmacogenetic screening strongly suggests that IVDs will assume an increasingly important role in detecting and managing an even broader range of diseases. They offer the prize of reducing the waiting lists from the opposite end to that generally processed by the healthcare system, and offer a real opportunity to reduce the overall costs of healthcare in a variety of scenarios. The challenge is one of information exchange, in an area of human endeavour already overloaded with news of advances and innovation. It is a challenge taken up by the British In Vitro Diagnostics Association, attracting significant encouragement from professional and administrative organisations as the evidence to support its position grows.

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In vitro diagnostic products and systems are used in medical practice for a variety of applications. As the name implies they are mainly used to determine (or diagnose) what is wrong with a patient. In addition, they have many other uses in the management of disease.

For example, to make sure that the treatment given is having the right effect, to ensure a proper match in blood transfusion and organ transplantation, to control that the levels of medicine given are providing the right amount in the circulation. They are used to detect infection and the presence of micro-organisms (bacteria, viruses and fungal diseases). They are used to screen populations at risk for hidden diseases that do not give symptoms. Similar products can also be used in health management. Pregnancy tests fall into this category.

However, there are many other tests that could be used more widely to check individual health status. Many of these are discussed in the press and for example in women's journals (often it is the women of the family who are most health conscious). Many similar or identical products are also used for applications other than the management of individual health and disease. For example similar tests are used for the detection of viruses in pooled blood for plasma protein production in the medicinal industry, as a part of the production process.

The tests are used in veterinary medicine, for pet animals, for farm animals. They are used widely in forensic medicine Non medical applications include environmental control (for example the control of water quality), for detection of contamination of food and raw materials (for example for traces of penicillin in milk), for detection of micro-organisms in the production of food and medicine.

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As new frameworks for patient care emerge, In Vitro Diagnostics hold the key to implementation and the opportunity to provide a cost effective health service to the nation.

In Vitro Diagnostics (IVDs) are the tests that protect our blood supply, monitor the levels of drugs we are given and provide information to assist diagnosis and treatment of our ailments. Government needs to be aware of the full facts concerning the difference diagnostics can make to success of the health service in clinical and financial terms. These tests, generally run in the pathology laboratories of our hospitals, can in some instances be carried out in doctors' surgeries, high street Pharmacists, and some even by patients themselves.

As more money becomes available to provide doctors, nurses, and new hospitals, the role of diagnostics becomes even more critical in providing accurate diagnosis to prevent waste of new, precious resources. Increasing the rate at which Cancer is diagnosed and treated will gain little unless the tests carried out in the laboratory to monitor treatment are properly funded. The management and reduction of the burden of Cardiovascular Disease, so well recognised in the new National Service Framework, requires the appropriate funding of IVDs to realise its goals.

Sickness is expensive to individuals and the health service. Early diagnosis of disease, achieved by testing those most at risk, can identify and allow treatment to begin avoiding later pain and suffering as well as saving healthcare resources. The risks of particular diseases themselves in an individual can also be estimated, and IVDs are again implicated in this important process.

Cardiovascular disease

Diabetes is a condition that is life threatening and consequently expensive when undiagnosed or untreated. One of the complications of this condition which remains undiagnosed in over one million citizens is heart failure. Clearly the use of diagnostics to find the missing million will also impact the incidence of cardiovascular disease. Other factors which influence the likelihood of cardiovascular disease include Cholesterol levels, Homocysteine levels, and genetic markers for predisposition to this condition. Changes in lifestyle, diet, and treatment can reduce these risks, IVDs allow objective measurements to support the individual and his/her medical advisors.

The use of IVDs for rapid differentiation of the causes of acute chest discomfort avoids the costs and distress of inappropriate hospitalisation, or the results of failing to diagnose life-threatening episodes. During intensive care, IVDs continually provide the medical staff with information upon which to treat and support the critically ill patient.

Cancer

Whilst the initiatives to improve the NHS performance in absolute and comparative terms in the area of Cancer management are welcome, the hospital laboratories need to be provided with the diagnostic tools to keep up with the increase in demand the implementation of these initiatives will cause. IVDs are used to monitor treatment, whether it be by testing the levels of biochemical cancer 'markers' in the blood, or by analysing the blood-cells themselves.

IVDs are also used to diagnose cancer, and can do so in the early stages of many tumours. For example, utilising a test for Human Papilloma Virus in conjunction with current cervical smear cytology would significantly improve the performance of the Cervical Cancer screening service, both in its accuracy and in the downstream savings in lives and costs. Another example is the use of blood tests that indicate the presence of prostate cancer, long before physical examination can do so, and before symptoms are reported by the patient.

Central to the successful implementation of the new National Service Frameworks, the role of In Vitro Diagnostics needs to be recognised and adequately funded. So doing will pave the way for the potential benefits of these new initiatives to be fully realised, in both clinical and financial terms.

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EVIDENCE BASED MEDICINE can be defined as the process of rigorously evaluating the effectiveness of health care intervention, disseminating the results and using these findings to influence clinical practice

The drivers for EBM are:

• A wide variation between clinical outcomes and costs
• A substantial amount of medical treatment is not supported by evidence of its utility
• Healthcare purchasers are now likely to buy on outcomes not on activity
• Governments wish to build health care around cost effective services based on robust evidence

The Clinical Laboratory in the UK is commonly costed as an overhead, not allowing for the potential cost utility of the services it offers to be realised. Much evidence already exists as to the down-stream benefits to the healthcare budget and the health of the individual of the use of laboratory medicine and IVDs. True measurement of healthcare outcomes will advance the understanding and implementation of this evidence.

Definitions of Cost in the Laboratory

Cost equalisation: replacement test to be costed at equivalent to the existing test, within the laboratory context. This reduces the ability to upgrade tests, but helps reduce the 'overhead' of the laboratory

Cost effectiveness: takes into account only the direct cost of the test, in respect to the effectiveness of the department. Allows the laboratory to trade staff costs for improved technology, but may lead to deskilling and reduction of staff

Cost benefit: considers downstream savings within the hospital context. A first step in recognising the benefits of the laboratory service, in reducing costs or improving efficiency elsewhere in the hospital

Cost utility: considers all costs and benefits, direct and indirect. The ultimate goal, where the overall benefits of laboratory medicine and the use of In Vitro Diagnostics are recognised

Measures of Outcomes The true value of IVDs can only be measured when healthcare outcomes are recorded and understood. Some examples of the way these may be measured:

Resource utilisation

• length of stay / diagnosis
• hospital days / 1000 population
• length of stay in ICU or CCU

Intermediate outcomes

• rate of screening/1000 population
• rate of incidence of targeted conditions

Long term outcomes

• patient satisfaction
• functional status of the patient
• quality of life
• return to work

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There is nothing new about genetic testing itself, but the technologies now available will allow a more reliable estimation of the risks of disease that individuals have because of their genetic make up. The ethical debate centers on whether we should use the tests and under what circumstances. There are numerous examples of use of genetic information that is accepted and supported widely.

Insurance companies have always had an interest in the family history and other simple indicators (for example weight in relation to height and blood pressure) in order to estimate the risk of invalidity or premature death that a new applicant for insurance may have. For example, it is common in Southern Europe for families to be tested for sickle cell anemia as part of genetic counselling before marriage.

BIVDA is an active member of a UK Forum which includes government bodies and the professions, brought together to discuss the impact on the NHS of implementing genetic services and the benefits of legislation in this area.

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Anyone who has visited a medical laboratory will know that it is a "high tech" world, with automated machines testing hundreds of samples a day. Many hundreds of sample components can be measured, but usually between two and ten are measured for each sample. Some tests (for example biological cultures) take time, but others can be carried out rapidly if there is an emergency.

The results are sent to the doctor in the form of a laboratory report for each sample that gives the results in comparison with normal values. In many cases the doctor will discuss the results with and request additional information from specialists in the medical laboratory.

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