The Death of Niall Rush - An Experiment in James Street

IT WAS COMING UP TO EIGHT O'CLOCK ON THE MORNING OF MONDAY MAY 28. AT 23 IONA ROAD, JOHN KENnedy was on the point of leaving for work, making van deliveries across the city and into the country. Shortly before he left the house he went into Niall Rush's bedroom to call him. Niall mumbled something to John, fell back to sleep. About two hours later, he was woken up by Shay O'Brien,· a friend of his who called to the house. Shay went down to boil the kettle, make some tea. Niall and Shay sat in the kitchen, had toast and tea, and discussed what they were going to do over the long weekend coming up. Shay was going to Kerry. Other people in the house were thinking about going to Donegal. Niall was undecided. He still had five days to make up his mind. The next five days he planned to spend in the Institute of Clinical Pharmacology in James Street.

Around 11.30, the two left the house to walk into town. Niall was expecting to meet some Spanish students in Bewleys. He talked about going out to Burton Hall in Stillorgan, meeting Joe Claffey in White Cross Clinic on the way back. He made an arrangement to meet Shay in Bowe's of Fleet Street at about 5 or 5.30.

At Burton Hall, Niall Rush received a deep intra-muscular injection of a slow-acting trannquiliser. The drug involved is intended as a slow release, and normally lasts two to four weeks.

He went once a month for this treatment.

On his way back from Burton Hall later that afternoon, he called into the Clinic to see Joe who was undergoing a drug test. From there, he went back into town by bus. He had borrowed £1 from a friend in lana Road that morning to cover the bus fare out to Burton Hall and back. He rejoined his Spanish friends in Bowe's, arriving there shortly before Shay at 5.10. All the usual people were not there on account of the time, and also because it was Monday. iall drank about three pints of Heineken with his friends and at 7 he left to get a bus to the ICP Clinic in the grounds of James Street Hospital. That day he was going in to complete the second phase of a two-part test.

It was three weeks earlier when Niall had gone in for the first phase. He had been in Bowe 5 with a large group and was due into ICP at 7. By that time, there was a bit of a buzz going with the crowd and he was reluctant to leave. He decided to call the Clinic and ell them he would be delayed. He talked for about five minutes on the phone, came ba La the bar and announced that he did not have to be in there until 8.30.

People present who had also been in there for tests made jokes about the place and about staggering in drunk. That had been the first phase. Now it was three weeks later and Niall was going in for the second time. There wasn't the same buzz in the place as there had been three weeks earlier. He lifted a bag over his shoulder containing clothes, books and writting materials, using his weight lifter type of act, exaggerating the weight of the bag. From the door of the bar he gave dramatic wave to the crowd left behind in the corner. He arrived at the Institute of Clinical Pharmacology at about 7.30pm.

Niall Rush spent that night in the Institute and some time between 8 and 10 on Tuesday morning, he was infused with Eproxindine 4/0089, a drug developed by a multiinational drugs company to regulate the rhythm of the heart, specially following heart attacks. By 10.15, Niall Rush was dead.

THE INSTITUTE OF OF CLINICAL PHARMACHOLOGY IN DUBLIN IS one of the top three centres of its kind in the world. The Institute exists as a profit making limited liability company and carries out phase one clinical drug trials for dozens of foreign pharmaceutical companies. Phase one trials are trials vhich are being conducted for the very first time on humans, having previously been tried only on animals.

Millions of people may be treated on the basis of results from clinical trials. Phase I clinical trials involve giving the irug to healthy volunteers. Phase IIA involves giving the drug to patients in a limited way. Phase lIB seeks to define the dose level. Phase III testing is full preregistration studies.

With the exception of Phase I testing, all the others are carried out in ordinary hospitals. All the teaching hospitals in Dublin carry out such tests. Between 20 and 25 hospitals in Ireland carry out such tests for drugs companies. Between 400 and 1,400 people may take part in all the various trials before the drug may be marketed in Ireland. In order to market a drug, it must come under the scrutiny of the National Drugs Advisory Board. However, even if a drug is refused for marketing, it may still be prescribed by a doctor and given to a patient.

Many different types of drugs have been tested in the Institute including anti-cancer drugs, anti-coagulants (to prevent blood clots), hormones, cardiac drugs, analgesics (painkillers) antibiotics, anti-depressants, diuretics (to alleeviate fluid retention) and most blood pressure drugs. The Institute was first set up in 1965 with the backing of the Swiss pharmaceutical company, Hoffman La Roche. Dr Austin Darragh was its director, and in 1979, Hoffman La Roche sold its interest. Dr Darragh now owns and runs . the Institute with managing director Dr Ian Brick and John Murphy, its financial controller.

Although the Institute is situated in the grounds of St James Hospital, there are no links between the two places. Dr Darragh intends opening a new Institute some distance from the present site with the aid of a £1.1 million IDA approved grant. The Institute employs just over one hunndred people and its operations extend into the White Cross Clinic at Stillorgan which carries out similar testing. The Elan Corporation based in Athlone, is another company which carries out tests on healthy volunteers. At one time or another, the following multi-national pharmaceutical companies have had clinical trials carried out for them in Ireland: Pfizer, Hoffman La Roche, Kali Chemie,Beechams, Janssen, Bayer, Squibb, Astra, Warner Lambert, Bristol Myers, Schering Plough, Revlon, Wellcome, G.D. Searle, Paarmuka, Boehringer, Ingelheim, Organon, Chemibiotic, Hoechst. The routine for a test for a company might go something like this:

A case arrives from the drug company. Contained inside, is the complete range of doses for each volunteer for the entire trial. Each individual would be marked out from start to finish, and the doses would have been made up by the drug companies in many cases. The protocol would also come with the drugs.

The protocol sets out the rationale for the test, why it is being done at all, and a description of the drug. It sets out how the subjects should be selected and what sort of people should be excluded by virtue of age or sex. The design of the study is also indicated - whether it is single or double-blind. (A single blind test is where the volunteer does not know what he is being given but the doctor does; a double-blind is where neither of them know what is being administered.)

The protocol also deals with the assessments to be made, how adverse effects are to be dealt with, and whether the samples taken will be anaalysed by the clinic or the company. At the end of the protocol, there is the "name and telephone number (day and night) of a doctor, usuallly in the country of origin of the drug, to be contacted in case anything goes wrong. Sometimes, in the case of double-blind tests, there is a sealed code accom panying the drugs in case of an emergency.

The Institute of Clinical Pharmachology in Dublin has about 1,000 volunteers a year, most of whom are male. Even though Irish women have the highest incidence of cardio vascular disease in Europe, these drugs are not tested on females. Volunteers are paid a standard £20 a day for their services. This works out at about 83p an hour. Grants to the ICP of up to 50% are available from the IDA if the drug under test is to be manufactured here.

In the 1970s, the Institute was known as a place where students could go if they wanted some handy money. Predominantly, volunteers were students taking time out to collect money for fees or rent or whatever. Towards the end of the decade, things began to change. The prevailing economic conditions left more and more 'people without work. without money. Unemployed Dubliners took advannrage of the £20 a day on offer from the Institute. A single employed person gets about £30 a week on the dole.

The prospect of £20 a day for, say, a 26-day straight test :tetal £520) must amount to an inducement. (It would take four months to get the same money from the dole.)

However, the main specification in paying volunteers for drug trials is that the inducement should not be too much. Even if the payment were less than £20 a day, it is likely that people would still put themselves forward as volunteers. The rate had not changed in the last five or six years, the value of the amount has decreased considerably, and there is no shortage of volunteers.

Joe Claffey and Niall Rush went to the fCP Limited in May this year to put themselves down to be tested for a drug to control Parkinson's Disease. On the consent form it is identified simply by the code MJ 13805. It was to be the first time the drug had been given toa human. The test was being carried out for the company Bristol Myers and was a tolerance study. (The doses given are increased with each administration.) One of the purposes of a tolerance study is to find out at what point the patient will exxperience adverse effects. A total of 18 people were to be taken in for 17 days. Each participant would receive £340. Clause 5 of the Consent Form states:

The health of an individual volunteer 'fill not be immproved by participation in any drug trial of this nature. On the contrary, some element, however small, of health and life endangering risk must always be involved in any study.

It will be the responsibility of the Institute and its clinical staff, to ensure by all possible means, that the health of the participants is safeguarded.

This is the standard clause on all consent forms. Accorrding to Joe Claffey, Niall Rush was turned down for the test due to the condition of his veins. The test involved taking a large number of blood tests over the period. So it was important that the volunnteers veins be in good order. Others, besides Niall Rush, were turned down as well.

The sam e day, however, Niall Rush was accepted to undergo the Eproxindine 4/ 0089, a different test.

Joe Claffey underwent his pre-medical on May 8, and was admitted on May 16. Claffey describes the effects of the drug as being like an electric shock to the system. The drug made you feel as if you'd slowed down. even when you walked. He had the impression that he was never going to arrive at the point he was walking to. Mentally, there were no noticeable side effects, they were all physical.

The test also involved doing cycometric tests. These are tests which attempt to measure motor responses to drugs. They are considered an indicator of how a person who had been prescribed the drug might act driving a car. These tests were taken three times a day every day. One test involved reacting when a light was switched on or off. Another test involved watching a circular tray of lights, knocking each one off as it was switched on. After taking the drug, the time taken to com plete these tests increased dramatically.

When Claffey was doing this test, he was given four carrdiographs a day, one cardiograph being done while lying down, one standing and one sitting, and three minutes between each reading.

There are many different tests performed at the Instiitute. They range from a once-off test lasting a few days. up to those lasting a month. Some of the trials are split with intervals of perhaps weeks between each session. Conditions for individual volunteers inside rhe Institute vary according to what drug they are on. Some volunteers might have to give, say, three blood and urine samples a day. For the rest of the time they could watch TV, play cards, read or whatever. Others might have to give more samples some might have a permanent needle into their arm. There is also a recreation room.

Meals are regular, breakfast, lunch, tea, supper. Some volunteers might have to fast in the morning with certain drugs. Volunteers on less exacting tests might sit around playing cards or chatting during the day. The Institute aas always had a reputation among some of the people who went in there. There were descriptions of cannabis smoking sessions. A few years ago, the Institute began doing THC rests, which would show up cannabis residue in the blooddstream. Anyone found to have a positive test would be deemed unsuitable to continue their test.

Other people had also undertaken the Eproxindine -4/0089 test. It was a split test. There was a gap of three weeks between two sessions. One of the others had been in three weeks before Niall Rush.

On the first session, he says, they were taken in at night, some days after their pre-medical. The following morning, they were given the drug. About one hour later, he experienced numbness of mouth and lips, taste distortion, loss of balance. Another volunteer suffered an acute attack of nausea.

NALL RUSH'S FATHER WAS AN AMBASSADOR; AND THE FAMILY SPENT TIME IN the United States, Nigeria and Portugal. He was born in 1953. Later on, he was sent to Gormanstown College. Sometime in the mid-seventies, he was diagnosed a schizoophrenic and was still under treatment at the time of his death. Over the last six or seven years he worked at a variety of odd jobs, including one as porter in a hotel. He lived in diITerent parts of Dublin, moving out to England and the Continent to stay with friends from time to time. Occaasionally, he did clinical drug trials in James Street, as did ztaay of his friends. He was not the healthiest of indivii;:uals, smoking up to 50grms of Duma roll-your-own a day.

Under the Coroners Act, when somebody dies and a medical certificate is not forthcoming, there is an investigation by the gardai,as agents of the Coroner. Following the death of Niall Rush, there was a port-mortem, performed by John Harbison the State Pathologist. Detective Inspector Connolly of Kevin Street Garda Station and Garda Joe McGarrity from Kilrnainham were put onto the case.

On the Saturday when Niall Rush was buried, Garret Fitzgerald broke off from Ronald Reagan's visit in Galway to attend the funeral. Barry Desmond, Minister for Health, and the man ultimately responsible for clinical drugs trials was also there. Hundreds turned up to the small church in Dalkey.

DAY BEFORE THE FUNERAL JOE CLAFFEY WAS DISScharged from the White Cross unit at Stillorgan. Claffey, a friend of Niall Rush's, had become clearly upset when he heard of the death on the previous Tuesday. A week later he went to the Institute of Clinical Pharmachology in James Street to collect his paycheque and undergo a post medical examination. There, he was told that Dr Brick would like to speak with him. He waited around for about half an hour. There did not seem to be much happening. There was no sign of Brick appearing. It was suggested that he might come back the followwing morning.

Later on that night, he met some friends, told them about Brick wanting to see him. They thought that the fact that he was a close friend of Niall's might have someething to do with Brick wantting to see him. It was decided, for a variety of reasons, to tape the interview. Sometime around ten the following morning, he went into the ICP.

Joe Claffey was wearing a combat jacket. In the left breast pocket was an old legal dictaphone. He was alone in the room with Dr Brick for a while and shortly after that Dr Darragh and Dr Walker came in. As he had come through the door of the building, he had pushed the button. Now there was a friendly conversation, how he felt about Niall's death and about how they knew he was upset and how shocked they were as well. At some point, they were asking him about whether or not he was aware that Niall used any other substance. They told him they had done a full specctrum test on Niall which had not revealed any suspicious substances. Niall's heavy smoking was discussed. After about twenty minutes the discussion came to an end. As he stepped outside the door, he turned the machine off.

There were three friends waiting in a car outside. They rewound the tape. There was nothing but static. He had pushed the button the wrong way. He psyched himself up once again, went back in. Dr Brick and Dr Darragh weren't around. Dr Walker was. Under questioning, Dr Walker addmitted that there were some good points being made. He said that he would take up the issue of examination of patients who were returning for the second part of a test with the people in the ICP. Dr Walker expressed a worry that volunteers might be having treatment from another doctor, which they would not disclose for fear of being refused for a course. He went on for a while about the difficulty of getting the truth out of would-be patients about their medical history and so forth ..

Dr. Walkker: But how do we get the truth, you know? We're not policemen. We're not here to beat people up. We re not ....

Joe Claffey: That's right, yeah.

Dr Walker: And I try to be as sympathetic as possible to anybody who comes in here because I know that ... that the money end of it ... and that's why I keep away from the money end of it, that I don't get involved at all. If a fellow's fit at all I would recommend him for admission. But if somebody has a past history of illness of any sort, or a psychiatric admission to hospital, how the hell am I going to get that out of them if they deny it.

When Dr Walker was pushed on the issue of testing for specific drugs that present in the bloodstream of a patient. he replied that the usual drugs had been looked for. the ones that could be bought on the street, cocaine. heroine. morphine. However, in coming in for the second pan: of a test, he admitted that the patients "could be on anything". He also expressed the belief that there should be some way of checking up on people who were outside the ICP and due back in for another administration of a drug.

Dr Walker wished Joe all the best, told him that he's been a satisfactory volunteer, that they'd never had any reason to complain about his performance. Joe said he might come backifthe money was more. 83p an hour is not great for the sort of work involved. He turned the machine off when he got back to the car. This time, he'd pushed the button the right way.

FOR THE THE PAST TWENTY YEARS, CLINICAL TRIALS HAVE BEEN TAKING place in Ireland. Responsibility for this area comes under the am bit of the Minister and Department of Health. Speciifically in relation to clinical trials, the National Drugs Adviisory Board acts on behalf of the Department and the Minisster. However, the NDAB does not necessarily approve each trial that takes place. It is not necessary for the ICP to supply details of tests to the NDAB for approval. In the Guidelines for the NDAB, set down in 1979, it states in relation to clinical trials:

"The two main objects of the Board's concern are:

(1) that no drug be made available for use until the Board is satisfied that it has passed reasonable tests for safety; and

(2) that no drug continues in use if there is reasonable doubt of its safety. .

In carrying out its tasks the Board is concerned to avoid providing a hindrance to the development, clinical trial and marketing of new drugs of acceptable toxicity."

It is thus clear that the NDAB cannot force the pharmaeutical industry, or the individual testing centres, to subbit their proposed trials for scrutiny. The NDAB estimates that 20% of all trials take place without their being informed. Since the death of Niall Rush, there has been an increase in submissions from testing centres to the NDAB.

One of the constraints on the Institute is the Ethics Committee. This is the Committee that decides whether or not it is ethically correct to go ahead with a test in a prooposed way. The Committee meets about once a month. sometimes twice, and pass about two to four protocols each time. Sometimes they turn back a test for alteration or modification. Invariably, the drug company will agree to the modifications. If they don't, the Institute just would not do the job for them. The reasons why a protocol might be sent back vary. The Committee might feel that too many blood samples were being taken, too many injections, the size of the dosage might be considered too large, or too frequent, they might recommend that subjects be kept for an extra day after their last dosage. The Ethics Committee is chaired by Professor Patrick Moore, Professor of Bio-chemistry at St James Hospital. Also on the Committee are Dr Jack O'Riordan, director of the National Blood Transsfusion Service, Rev Edward Kelehan SJ, Dean of Residence in Hatch Hall, Mr Arthur Lavery (Secretary), solicitor, Mr J,1. Nolan, recently retired director of the hospital care programme of the Eastern Health Board, Mrs Elizabeth Doyle-Kelly, Dr Michael Buckkley, consultant physician to St James Hospital and Mrs Carmel Hennelly, Matron of the Institute of Clinical Pharrmacology. Professor Alan Browne, professor of obstettrics and gynaechology at the Rotunda is still a nominal member of the Committee but is not attending due to other commitments. All of the members of the Ethics Committee were invited on at the request of Dr Darragh.

In general, all drug trials take place under an informal agreement between the drugs industry and the Department of Health. There is no legal basis for this agreement. Just over a year ago, the Department said that there was legislaation pending to cover the area of clinical drug trials. At that point, it was not stated what shape the legislation would take - whether or not it would follow the legislation in Germany or the United States. (Following amendments to the Food and Drug Act in the US,.many pharmaceutical companies took their testing overseas due to the controls that were placed on them.)

Shortly after the death of Niall Rush it was envisaged that the proposed Bill would include some sort of licensing system. On June 25, Barry Desmond stated that "no trials should commence unless they had been notified to the National Drugs Advisory Board .... "

The Department says that the draft legislation is now at an advanced stage. However, following extensive discussions and consultations with various interested groups such as the NDAB, the bigger hospitals in the Dublin area, and the pharmaceutical industry, it has been decided to change the direction of the proposed Bill. It is now intended to have "a statutory clearance scheme" instead of licensing, according to the Department. The Department refused to say what this means. •