Research is of vital importance in preventing and treating disease. Many of the marvellous therapeutic advances that we often take for granted would simply be inconceivable were it not for a massive research effort around the world.

When we are entrusted with the treatment of many patients suffering from a rare disease such as uveal melanoma, we are also expected to learn as much as possible from our unique experience, to improve our practice and to share our findings with the rest of the world.

Our remit is not only to treat the patients with uveal melanoma who come to Liverpool but also to help the patients who are being treated elsewhere. It is a give and take relationship in that we benefit from the teachings of others and reciprocate by sharing our own discoveries with others.

In general, research is conducted in the following way:

1. A vague impression is defined into a discrete idea or statement (ie, 'hypothesis').
2. Measurements and observations are meticulously performed and recorded, being very careful to accumulate an accurate and complete collection of information or data (ie, 'database'). Special precautions are taken to ensure that the data are a fair representation of reality and not distorted by any 'bias' caused by selectively including some bits of information and leaving out others.
3. The data are then analyzed statistically so as to determine whether any results are due to chance or whether they represent an association between one event and another, (for example a treatment and an outcome).
4. Whenever possible, the mathematical results are supported by photographic evidence, which also helps bring things to life so that any message is understood more easily.
5. Any important finding is broadcast to other interested workers by means of lectures at conferences and in other hospitals, publications in textbooks and scientific journals, and, increasingly, on computer programs and over the internet.

Clinical research
The clinical research that we tend to do at the Ocular Oncology Centre in Liverpool consists of (1) evaluation of different forms of treatment and (2) case reports.

There are three factors that give us a unique opportunity to perform clinical research:

• Large patient numbers;
• Wide treatment choice;
• Good database management.

Patient numbers
Our Centre is one of only half-a-dozen centres worldwide where more than 200 new patients with uveal melanoma are treated each year. The large patient numbers allow studies to be completed more quickly and make it possible to analyze data more precisely, enabling questions to be answered using statistical methods.

Treatment range
Other centres tend to offer one or perhaps two different kinds of conservative treatment whereas we are able to perform all established forms of treatment: plaque radiotherapy; proton beam radiotherapy; trans-scleral local resection; trans-retinal local resection, and phototherapy. Such a wide choice of treatments improves the chances of success, firstly, because we are better able to match the treatment to the patient, and, secondly, because we are able to combine different treatments so as to get the best results.

Database
Our database must contain one of the largest collections of information on uveal melanoma in the world, with data from more than 2000 patients extending back in time as far as 1970. It was first established in 1985 and has continued to develop since then, with the help of professional software consultants.

In 1992, the database was completely upgraded to a new system, which has continued to evolve.

Since 1987, this database has been maintained by a succession of data managers, who have also ensured that the database is as complete as possible by collecting information from referring hospitals, general practitioners, cancer registries, and the patients themselves.

In 1994, a terminal was installed in the outpatient clinic for clinical information to be saved just after each patient is seen thereby minimizing the chances of any errors so that the data are as accurate as possible. A key to the success of the database is the way in which it is in constant daily use so that any errors quickly come to light. The database is used by our secretary for writing letters, organizing clinics and theatre lists. It is also used by our nurse, when she needs to communicate with patients or when a new patient asks to speak to a previously treated patient. It has often proved invaluable in patient care, for example, if the case sheet is not available when a referring ophthalmologist phones 'out of the blue' with a clinical query about a patient or if the patient's case sheet is not available in the clinic, perhaps because the patient was originally treated in Glasgow.

Our clinical research has tended to report the results of our various forms of treatment, correlating outcomes such as survival, conservation of the eye, preservation of vision, and tumour control with pre-treatment characteristics (ie, 'variables') such as patient age, pre-treatment vision, tumour dimensions and so on. These studies have enabled us to inform other specialists about what can be achieved when a patient presents with a particular problem. It has also made it possible for us to advise patients on their own prospects for success, after a particular treatment, so that they have been able to select the best treatment for their own particular condition. Importantly, this research has demonstrated to us the major complications after each treatment and the circumstances likely to give rise to these complications so that we have been able to develop ways of avoiding such problems.

The second form of research is to prepare a 'case report' if a patient presents with a very unusual condition. Case reports are useful for drawing attention to the existence of unusual clinical findings, rare tumours and unexpected outcomes after treatment.

Basic science research
Basic science research is essential for understanding the cause and the behaviour of uveal melanoma. The availability of numerous tumour specimens from our patients treated by local resection or enucleation creates opportunities for making a contribution to current knowledge in this field.

Several years ago we decided that if patients had a voice and knew what to ask of us they would encourage us to do more to than just treat the eye to prevent metastatic disease. We collaborate closely with a scientist with special expertise in tumour genes (ie, 'cytogenetics'). She has been investigating abnormalities in chromosome 3, which have a profound influence on survival.

We have also been collaborating with scientists at The Institute of Cancer Research , who are investigating whether certain genetic abnormalities contribute to the formation of uveal melanoma.

The Ophthalmic Oncology Group
Collaboration between ocular oncologists from around the world creates opportunities for sharing clinical and laboratory data, making it possible to investigate rare situations, which cannot be adequately dealt with by any individual centre. In 1992, the European Organization for Research and Treatment of Cancer (EORTC) established the Ophthalmic Oncology Group so as to foster collaboration between centres. Our Centre has played an active role in this organization since its inception.

Precautions
Several precautions exist to safeguard the rights of patients. Before any research project can be started, it is necessary for us to complete a detailed questionnaire and to submit this to the hospital's Ethical Approval Committee for scrutiny. This independent committee ensures that the research is feasible, well planned and worthwhile. It also checks that the project is safe and that any risks are fully justifiable when considered in relation to the potential rewards. It also checks any patient consent forms to confirm that patients participating in the study are given every opportunity choose sensibly whether or not they should participate.

According to the Data Protection Act, every patient has the right to view any information held about him or her.

Strict guidelines exist to ensure that patient confidentiality is respected at all times and that any results are published with full patient anonymity. If it is necessary to publish a photograph of a face, then parts of that face are either blotted out to prevent the patient from being recognizable or, if this is not possible, the patient's signed consent is obtained.

There is an increasing tendency to obtain signed consent from all patients, whether or not they can be identified from the photographs. In addition, there is a trend towards obtaining signed consent for the use of tissue specimens and even clinical information for research purposes.

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