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14 Mar 2003 : Column 598—continued
Mr. Dismore: Further to that point of order, Mr. Deputy Speaker.
Mr. Deputy Speaker: Order. I think that I can probably deal with this.
The hon. Member for Buckingham (Mr. Bercow) and the right hon. Member for Bromley and Chislehurst (Mr. Forth) will not expect me to have an encyclopaedic knowledge of every event that has occurred in the Chamber and in the Division Lobbies in past years, but I think that I can safely say that what has happened is not without precedent. With regard to what may happen outside the Chamber in terms of persuading right hon. and hon. Members whether and how to vote, there has been a multitude of precedents for such encouragement. We should now proceed.
Sex Discrimination in Private Clubs Bill
Order for Second Reading read.2.27 pm
Mr. Chris Mole (Ipswich) rose—
Mr. Deputy Speaker (Sir Alan Haselhurst): Does the hon. Gentleman have the permission of the hon. Member for Gloucester (Mr. Dhanda) to speak on his behalf?
Mr. Mole: I was about to say that, with the leave of the hon. Member for Gloucester (Mr. Dhanda), I beg to move that—
Mr. John Bercow (Buckingham): On a point of order, Mr. Deputy Speaker. I am sorry to trouble you, and I certainly do not want to test your legendary stoicism and patience, but is it proper practice for a Bill's promoter not only to be absent but to have arranged for another hon. Member to speak on his behalf, and to fail to apologise for, still less to explain, that absence? This is an extraordinary abuse of parliamentary procedure.
Mr. Eric Forth (Bromley and Chislehurst): Further to that point of order, Mr. Deputy Speaker. A moment ago, you referred to precedent and practice in the Chamber. I think that you will agree that I am a pretty assiduous attender on Fridays in particular, although I like to think that I am an assiduous attender on every sitting day of the House, but I cannot myself remember the last occasion on which an hon. Member with a Bill on the Order Paper on a day such as this, that Bill having been manoeuvred into place by that hon. Member's colleagues, apparently casually failed to be here and did the House the dishonour and disrespect of passing the buck to one of his colleagues who is here in his place. Is there nothing that can be done to defend standards in this House of Commons? What on earth is going on these days when hon. Members are apparently so casual in their attitude to their responsibilities?
Mr. Deputy Speaker: It is certainly not without precedent. Indeed, it could even be said to be quite a regular occurrence that an hon. Member asks another hon. Member to move a Bill on his behalf. That is not unknown. On this occasion, I understand that Mr. Speaker was notified in advance. As to any special circumstances applying on this particular day because of other procedures followed by hon. Members, I cannot say whether that adds to or subtracts from the occasion, but it is not unknown for one hon. Member to speak in place of another.
Mr. Bercow: Further to that point of order, Mr. Deputy Speaker. Further to your ruling, I am concerned about the propriety, in the widest sense, of the procedures of this House and the proper observation of etiquette. May I trouble you to advise the House whether, in terms of conformity with the usual courtesies, it is acceptable for a substitute Member to request a Second Reading for a Bill without any explanation of, let alone apology for, the absence of the promoter?
Mr. Deputy Speaker: I think that the hon. Gentleman did not give the hon. Member for Ipswich (Mr. Mole) the chance to make any such remarks, as he may have been disposed to do.
To be read a Second time on Friday 4 April.
Remaining Private Members' Bills
FOOD LABELLING BILL
Order read for resuming adjourned debate on Question [7 March], That the Bill be now read a Second time.
Debate to be resumed on Friday 11 July.
CROWN EMPLOYMENT (NATIONALITY) BILL
Order for Second Reading read.
To be read a Second time on Friday 21 March.
Ciproxin
Motion made, and Question proposed, That this House do now adjourn.—[Mr. Heppell.]
2.31 pm
Sandra Gidley (Romsey): I welcome the chance to put before the Minister my concerns about a clinical trial that took place in 1993 and 1994 in Southampton general hospital and other hospitals throughout the country. While some may think that there is no advantage in raking up history, some serious questions about the trial remain unanswered. Those questions are not only about the actions of Southampton general hospital, but cover wider aspects of the nature of clinical trials and how the safety of the public is safeguarded.
I was first alerted to this issue by a constituent, Dr. Steven Karran, who was at one time a member of the ethics committee at Southampton general hospital. At that time, I did what most constituency MPs would have done and wrote a number of letters about the subject. What then concerned me was that my letters to Bayer, the drug company, were not satisfactorily answered. A similar situation arose with regard to my letters to the Medicines Control Agency. Finally, when I asked the medical director at Southampton general hospital for an appointment to discuss the issue, I was passed from pillar to post, and to this day, that discussion has not taken place.
I should like to stress that that is highly unusual. In all other matters, staff at the hospital have been unfailingly helpful and they are usually only too willing to discuss whatever concerns I may have. Needless to say, I smelt a rat. Hence, I requested today's debate in the hope that the Minister would be able to obtain satisfactory answers where I have so far failed and that he would not be fobbed off as I have been.
I need to set this story in context, as some of the events leading up to the clinical trial in question are of great significance. I shall use the term "Ciproxin" to describe the drug throughout this debate. That is the easier-to-say brand name of a drug called ciprofloxacin, which is an antibiotic with a wide variety of uses. The drug is made by a company called Bayer.
The story starts in 1987. At that time, the ethics committees in Wessex were informed by Bayer that the Medicines Control Agency had issued a licence commonly known as a CTX for a 300-patient study of antibiotic protection in patients undergoing gall bladder surgery. The drug used was Ciproxin. The trial took place because Bayer was aware of something called the Flowerdew studies on a related drug, which had indicated a much higher than expected number of post-operative infections. It had also been shown that the blood levels of the drug were lower than expected, and that was thought to be the case because the drug had been administered at the same time as other pre-meds—drugs that are given in advance of a surgical procedure involving anaesthetics.
The drug company wanted to find out what effects the pre-meds had, so the licence that was issued was conditional on Ciproxin being given 60 minutes before the administration of any of the other commonly administered drugs that are routinely given on that basis.
The interval of an hour was determined on the basis of studies of Ciproxin in the blood. The drug was administered and blood samples were taken to establish the length of time it took before the drug levels in the blood were high enough to take effect. Delaying the administration of the pre-med for an hour meant that the drug had a chance to reach a level at which it was clinically effective. That is not the case when the drugs are administered together. Giving various drugs at different times before an operation affects the demands made of staff on a busy surgical ward. If all the drugs cannot be administered at the same time, the work load doubles.
The clinical studies showed that, when given well in advance of any other pre-med, orally administered Ciproxin can provide good protection from serious post-operative infections. Bayer published those results in 1989, and staff at Southampton and Glasgow were well aware of the results.
Now we reach the interesting part. In 1992, Bayer submitted a detailed protocol to the MCA to study the use of orally administered Ciproxin to prevent serious post-operative infections caused by elective or planned large bowel surgery. The septic risk of such surgery is five times greater than that in the previous study.
Professor McArdle, who is based in Glasgow and had been involved in the earlier research, wrote and designed the study. Bayer was also involved. There is no evidence of new studies that show the earlier study to be flawed. No evidence shows that the pre-med problem was anything but real. Yet the new study, which Bayer largely funded and supervised, ignored the known pre-med problem.
If the MCA was doing its job properly, it should have known about the pre-med problem. I have written to the organisation and its letter to me is a masterpiece of obfuscation. It claims that it was not allowed to provide information because it was given in confidence. We are considering a matter of public safety and interest, but we cannot find the answers or have proof of the study's findings.
I want to ask the Minister some crucial questions. Did the MCA grant a licence to Bayer in 1992 to undertake extensive clinical trials in elective large bowel surgery, using orally administered Ciproxin tablets to prevent post-operative infection? Did Bayer declare in its licence application the problem caused by the simultaneous application of other pre-med drugs? Bayer identified that problem in 1986, and it led the company to conduct a trial in which the antibiotic was administered before other pre-med drugs. Will the Minister undertake to let me see the application so that any shred of doubt about the trial can be laid to rest?
I am not sure who constitutes the villain of the piece. Is it Bayer through acting fraudulently? Is it the MCA, which made a mistake by letting the trial go ahead? Was somebody not on top of the job, and unaware of an earlier trial? I am not sure who is covering up for whom. Despite all the known doubts, the MCA issued a CTX to Bayer, granting it permission to undertake clinical research in 850 patients. That means that 850 patients will be put at greatly increased risk of contracting a severe post-operative infection.
There is some dispute. I have a sworn statement from Dr. Karran, who says that he has seen evidence that 46 per cent. of the 60 Southampton patients in the trial were adversely affected and contracted post-operative infections. However, in a letter to me, Bayer claimed:
- "The results of the study as a whole also indicate that the rates of post-operative infections were similar between patients receiving ciprofloxacin . . . and those receiving the other, commonly used antibiotic combination. The rate of early post-operative wound infection, the primary goal of this treatment, were low and equivalent in both treatment groups."
Before I became a Member of Parliament, I was a pharmacist. I was regularly inundated with drug representatives' glossy literature, which selectively quoted bits and pieces of the latest research that showed their product in a marginally better light than its competitors. This job can make one cynical, but I suspect that if the results of the trial had shown Ciproxin to good advantage, the research would have been published.
That raises another fundamental question that has a significant impact on public safety. Should the onus not be on drug companies to publish the results of any clinical trial, so that the information is in the public domain and can inform the wider debate? The answer that is always given is "commercial sensitivity". I understand the need for that in the short term, but the argument does not stand up in regard to the longer term. What price do we actually put on patients' safety?
Dr. Karran was on the ethics committee at Southampton hospital when the 1992 proposal was presented to the hospital in October 1993. He had been involved in the previous trial, and was therefore well acquainted with the potential problems of the proposed trial. Once aware of those problems, the ethics committee rejected the original protocol.
In an attempt to be helpful, Dr. Karran said he would be happy to support the trial if the Ciproxin was given separately from the other drugs. The professor in charge of the trial told the committee that the Southampton amendment would be followed by him and his research team. The study was therefore approved on the amended basis only. Bayer failed to act until June 1994. At that stage it admitted the existence of a potential problem, and informed all ethics committees of hospitals taking part in the trial except the one at Southampton. Why did it wait so long?
It may be asked why there was a problem if the protocol had been rejected. Unfortunately, in November 1994 Dr. Karran realised that the trial was going ahead under the rejected protocol of 1992 rather than the revised protocol of 1994. That was particularly serious because at the time most patients at Southampton received at least one of the pre-med drugs known to cause problems. A leaflet issued to patients undergoing the trial told them that they would be well protected against all post-operative infection—not just the wound infection that Bayer mentioned. Bayer denied that, but I have seen a copy of the letter given to patients. It says
- "Either way you will receive medication with an active substance so that you are well protected against any post-operative infections".
This is where it all starts to get a bit murky. Dr. Woodcock, who was secretary of the ethics committee at the time, wrote to the professor in charge of the trial at Southampton saying that the trial could go ahead subject to the necessary amendments. The professor wrote a letter in reply, parts of which were read out at an ethics committee meeting. Dr. Karran was under the clear impression that Bayer was happy to go along with the amendment. No one saw anything in writing at the time, but the decision was minuted.
It is alleged that Bayer contacted the professor in charge of the trial saying that it did not want to change the protocol, and could not proceed until the objections were released. Indeed, it is said that Bayer refused to supply the drugs until that was done. There is obviously a financial aspect, but I will be honest and say that it is not my major concern and I do not know what payments have been made and to whom. Anyway, the unamended trial went ahead somehow. Dr. Karran found out about it by chance in November 1994. The patients involved in the trial had all been informed in writing that the protocol had been approved by the Southampton ethics committee, which clearly was not true: the protocol used was the one that had been rejected.
That constitutes a major violation of the declaration of Helsinki—the European code of good practice. The first basic principle states
- "Biomedical research involving human subjects must conform to generally accepted scientific principles and should be based on adequately performed laboratory and animal experimentation and on a thorough knowledge of the scientific literature."
- "Every biomedical research project involving human subjects should be preceded by careful assessment of predictable risks in comparison with foreseeable benefits to the subject or to others. Concern for the interests of the subject must always prevail over the interests of science and society."
Bayer withheld critical safety information. It successfully deceived all other ethics committees in the UK and the Netherlands, as well as a number of physicians, nurses and pharmacists. Why did it all happen? It is often useful to consider motivation when trying to get to the bottom of a problem. Bayer's motivation is clear. Antibiotic cover for surgery was usually given by injection, which was costly and time-consuming. If the injection could be replaced by a tablet that was easy to administer, there would be a comparatively simple and cheap alternative—and the Minister knows as well as anyone the financial pressures on the NHS and our hospitals. There was huge sales potential if a licence could be obtained for oral use of the drug for routine prophylaxis. Hence the trial.
Unfortunately, the drug's potential was spoilt because it could not be given at the same time as other pre-med drugs, and the inconvenience to staff presented a major hurdle. There was, therefore, a huge incentive to try to establish a trial during which the administration of the drugs was not separated. Unfortunately, commerce appeared to win over ethics, with a drive to operate the trial in the manner that Bayer wanted rather than in the manner that the Southampton ethics committee had recommended.
The motivation of the senior medical personnel at the hospital at that time is less than clear. Medical trials are usually expensive and bring a certain amount of kudos, although, as I have said, I have not looked at that aspect of the case in depth. The motivation of my constituent, Dr. Karran, is clear. I have now known him for nearly three years, and his story has not wavered in a single detail. Quite simply, he wants the record put straight. The motivation of the senior management of the hospital is also unclear, but this appears to be one of those occasions on which serious doubts were raised by Dr. Karran, but not properly investigated. There has been an internal inquiry, but no one has really come forward. It is unclear whether the problems were financial, or whether there was a closing of ranks among a group of high-level staff.
So far as my motivation is concerned, I was originally helping a constituent, but, as time went on, I became intrigued by the lack of co-operation from some agencies and the lack of information coming from the Medicines Control Agency; there was an almost complete wall of silence. I then realised that the case could have wider implications, and that lessons could be learned that would be applicable to the many other clinical trials taking place at the moment. The MCA's behaviour in this matter does not inspire consumer confidence. The agency should protect the public from fraudulent and potentially misleading information, but it has clearly failed to do so in this case. Whether that was through incompetence or by deliberate intent is unclear. The public audit trail is non-existent, so it is almost impossible to get to the bottom of this matter. Do not the public deserve better?
I am also concerned about the actions of Bayer. As I said earlier, I believe that, in the interests of public safety, details of all clinical trials should be in the public domain. The current position is that the MCA has investigated its files but has repeatedly refused to disclose the relevant information, citing confidentiality and the code, although it has intimated in writing that the information provided by Bayer and McArdle in 1992 for the colorectal CTX was incomplete. We know that a licence was issued by the MCA, but one critical question remains unanswered. When making that application, did Bayer declare the problem caused by the simultaneous administration of other drugs used for the pre-operative preparation of patients? Does the Minister agree that, if Bayer did not declare the problem, its action was fraudulent and that some sanction should be taken against the company? If the problem was declared, will the Minister undertake to provide me with a satisfactory explanation as to why the MCA allowed the trial to go ahead, knowing the risk to the public? Who made that decision, and how could that person justify putting the lives of up to 800 patients at risk?2.47 pm
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