Roughton v Weston Area Health Authority & Ors

This is an appeal against the decision of Mr Justice Owen in a judgment dated 17 November 2003 to dismiss a claim for damages by Adelaide Roughton (‘the Claimant’) against general medical practitioners and a health trust. In April 1998, when she was 35 years old, the Claimant suffered an acute and severe episode of cerebral vasculitis which caused extensive damage to the brain resulting in severe and permanent disability.

The issues at the hearing were narrowed because, shortly before its commencement, breach of duty was admitted on behalf of two of the general practitioners, Dr Graveson and Dr Anderson, who were the second and third defendants (“the defendants”). The concession and its effect were stated by the judge:

“…but for the admitted breach of duty, the Claimant would have been admitted to Weston General Hospital on 17 April and transferred to Frenchay Hospital within at most 48 hours, and that accordingly the sequence of examinations and treatment at Frenchay Hospital would have been advanced by about 48 hours so that treatment with intravenous steroids would have been started on 20 April as opposed to 22 April, and with cyclophosphamide on 24 April as opposed to 27 April.”

The claimant’s case is that the delay in treatment caused a major exacerbation of her brain damage. The issue, as correctly put by the judge, was: “Would earlier treatment have reduced the damage to the brain suffered by the claimant and if so to what degree ?”. It is common ground that the treatment regime at Frenchay Hospital was appropriate and reflected the conventional approach to the treatment of cerebral vasculitis and allegations against the first defendants (and fourth defendant) were not pursued.

Cerebral vasculitis is a very rare condition involving inflammation of the blood vessels within the brain. Its aetiology is not fully understood. It is generally viewed as a mal-adapted response of the body’s immune system to some insult. The judge cited Dr J W Schmidley (Vascular Diseases of the Central Nervous System, Chapter in Neurology in Clinical Practice, Bradley et al) who stated that it manifests itself in “progressive, cumulative and multi-focal neurological dysfunction”. The neurological dysfunction is a result of reduction in blood flow to the brain cells. If it drops to a level where cellular integrity fails, cell death, which is irreversible, occurs.

The judge carefully set out the sequence of events and made findings, which are not challenged in this court, as to when the brain damage occurred. An MRI scan was carried out at Frenchay Hospital on 22 April 1998. At 14:30 hours on 27 April, the claimant underwent cerebral angiography. A further MRI scan was carried out on 6 September 1999. It was important to establish the time at which damage occurred. The judge concluded:

“22.

The question is whether there is unequivocal evidence of permanent damage in those areas of the right side of the brain controlling motor function on the left side of the body in the period between the MRI scan on 22 April and the deterioration commencing at 1300 on 27 April, as opposed to fluctuations in motor control indicative of ischaemia. On this issue I prefer the evidence Dr Bamford that there is no such unequivocal evidence of infarction, and of Professor Warlow whose analysis of the medical records in his report to the court led him to the conclusion that she deteriorated on 27 April and to agree in cross-examination that her condition was fluctuating up to 26 April.”

The judge then considered the claimant’s left-handed visual deficit and concluded:

“It follows that in my judgment the permanent brain damage, additional to that revealed on the MRI scan of 22 April, is on the balance of probabilities to be attributed to the deterioration in the claimant’s condition on the 27 April.”

But for the damage on the 27 April, the claimant would have had significantly greater mobility and visual acuity.

The judge restated the issue on the basis of his findings:

“29.

Would earlier treatment have reduced the degree of permanent damage and hence the degree of disability ?

The issue is whether the commencement of treatment by intravenous steroids on 20 April rather than 22 April, and cyclophosphamide on 24 April rather than 27 April, would have made a difference to the outcome. Given my conclusions as to the timing of the brain damage, the issue can be further refined, namely whether earlier treatment by one or other or both of the drugs in question would have prevented the deterioration on 27 April.”

The court has been referred, as was the judge, to the neurological observation charts and the clinical history sheet for 27/28 April and the course of events is substantially agreed:

(a)

There was no significant deterioration in neurological condition between 22 April and 27 April.

(b)

The deterioration on 27 April, to which the judge referred, began at 13:00 hours.

(c)

At 14:00 hours, the claimant underwent an angiogram. That confirmed an “acute deterioration today”. At 16:00 hours, it was noted that the patient “has deteriorated over past couple of hours”.

(d)

In the clinical history sheet it was recorded at 17:00 hours, the entire note being underlined:

“P/C to husband

1.

Told him of D of cerebral vasculitis

2.

Explained that we are very concerned about her condition and that she may not recover

3.

Explained that we are actively managing her and have added cyclophosphamide.

(e)

It was also noted that the patient had “severe cerebral vasculitis” and that “conscious level has deteriorated this afternoon”.

(f)

At 17:15 mannitol was given. That is a diuretic given to reduce brain oedema acutely and produced an improvement for probably a couple of hours.

(g)

At 18:00 hours, cyclophosphamide was given.

(h)

By midnight 27/28 April, the condition had stabilised.

(i)

The condition remained stable thereafter.

On the point remaining in issue, evidence was given on behalf of the Claimant by Dr J Bamford, Consultant in Neurology and Cerebrovascular Medicine, and by Professor C Warlow, Professor of Medical Neurology. On the question of causation, Professor Warlow described himself as a “committed don’t know”. (The court has not been supplied with a transcript of his oral evidence.)

Against that background and on the evidence, it was and is submitted by Mr Havers QC on behalf of the defendants:

(a)

The stability was most unlikely to have been achieved by the steroids. If they had not produced results since 22 April they are unlikely to have produced results on 27 April.

(b)

The stability could not have been achieved by the cyclophosphamide because it was administered only a matter of hours before stability was achieved.

(c)

There is no evidence that it was either of the drugs, or the drugs in combination, which produced stability. A spontaneous recovery is more likely.

(d)

There is no evidence that cyclophosphamide had beneficial effect after 27 April.

The judge stated his conclusions at paragraphs 42-48:

“ 42. As to steroids [Dr Bamford] said in the course of his evidence-in-chief that “… most neurologists would say you give intravenous steroids for 3 to 5 days to see if you get a response.” It was no doubt on the basis of that evidence, together with the fact that the administration of steroids for 5 days did not prevent the deterioration on 27 April, that led to his agreeing with Mr Havers QC that the administration of steroids two days earlier would be unlikely to have made any difference to the outcome.

43.

Secondly he accepted that the improvement that in fact took place from 2100 on 27 April could not be attributed to a dose of cyclophosphamide given at 1800 hours. He also accepted that the improvement at 18:30 was due to the mannitol given at 17:15, and that mannitol is a short acting drug used to reduce intercranial pressure in an emergency that would have been effective for two hours at the most. In those circumstances it must follow that the improvement on the 27 April was spontaneous.

44.

Thus I am bound to conclude, contrary to the argument developed by Dr Bamford in the course of his evidence that her condition was of such a nature that spontaneous recovery was unlikely, that the Claimant’s condition was capable of spontaneous improvement. Secondly there is no evidence to suggest that the administration of cyclophosphamide had a beneficial effect, given that her condition had stabilised by 24:00 hours on the 27 April. It follows the course that the disease ran does not provide support for the contention that there would have been a more favourable outcome, and in particular that the deterioration on the 27 April would have been avoided, had cyclophosphamide been administered on 24 April.

45.

Accordingly there remains only the assertion by Dr Bamford based upon his own clinical experience and that of others, that earlier administration of the drug regime would have made a difference. But as mentioned above his experience was limited to a single case in which as he put it, no doubt choosing his words with care,

“The recovery appeared (my emphasis) to be due to that combination of intravenous methylprednisolone, cyclophosphamide.”

And as he agreed in cross-examination –

“… no one actually knows for sure whether the cyclophosphamide improves the condition for sure.”

46.

His discussion with colleagues was with those who treat systemic vasculitis rather than the form isolated within the central nervous system. Finally, and as was submitted on behalf of the defendants, the literature is of very limited assistance given the very small numbers involved and the absence of therapeutic trials.

47.

What if any reliance can be placed upon the fact that the treatment used in this case is accepted by neurologists as the appropriate treatment for cases of cerebral vasculitis ? The position was succinctly summarised by Professor Warlow who explained that the combination of steroids followed by cyclophosphamide is the approach that he would use “In the absence of any thing else to do. And on the basis of fragmentary evidence.” Whilst it is obviously a rational approach based as it is upon the approach adopted by those treating systemic vasculitis, I do not consider that it provides a basis upon which to conclude that it would probably have been effective in the Claimant’s case.

48.

Given the clear evidence that administration of steroids did not prevent the deterioration on 27 April, and secondly that the improvement following the deterioration cannot be attributed to cyclophosphamide and that there is no other evidence of cyclophosphamide having had an effect, I am driven to the conclusion that the Claimant has failed to prove that to have commenced treatment at an earlier stage would have affected either the course that the disease ran or its outcome. It follows that her claim must fail”.

The issue is as to what would have been the course of events if the drugs had been administered earlier than they were: two days in the case of steroids and three days in the case of cyclophosphamide. On a balance of probabilities, would the substantial deterioration in the claimant’s condition which occurred on 27 April have occurred ? Mr Havers emphasises the need to look at the facts of the particular case. The judge was correct to reach conclusions on those facts in paragraphs 43 and 44 of his judgment, he submits, before, as he did in paragraphs 45 to 47, considering the broader picture.

In my judgment, any consideration of the effects of taking a drug upon an illness or disease, and of when those effects are likely to occur, requires knowledge of the illness and of the drug. In many cases the characteristics of the illness, and of the drug, and of the effect of one upon the other, will be very well known and the effect of administering the drug, and when the drug will have that effect, can be predicted with near certainty or a high degree of probability. In this case, the drug is well known; it is used to treat cancer and also it is toxic and may have adverse side effects. What is far less well known is the disease or condition cerebral vasculitis which fortunately is very rare. Dr Bamford had only treated one case similar to this one and Professor Warlow none at all. The effect of cyclophosphamide on the condition, and when that effect will occur, cannot be predicted with certainty, as Dr Bamford acknowledged in evidence. The facts of the particular case can only be considered, however, in the context of medical knowledge and opinion on those matters, whether that knowledge and opinion are complete or only partial and provisional.

The issue was whether, on a balance of probabilities, the achievement and maintenance of stability in the claimant’s condition after the serious deterioration on 27 April was spontaneous or was caused by the steroids and cyclophosphamide, either alone or in combination. Professor Warlow was no doubt mindful of these considerations when he commenced his report of 7 August 2003 by stating that: “because isolated cerebral vasculitis is such a rare disorder, to prepare this report I have had to rely less on experience of a handful of cases in my professional lifetime and more on the original scientific literature”. It does not necessarily follow that the judge’s conclusion was wrong, but he was not in my judgment correct to relegate his consideration of general medical knowledge until after he had expressed the conclusion that the improvement, or stabilisation as it was more appropriately described by the judge at paragraph 44, was spontaneous.

The medical literature produced to the judge was remarkably consistent in its view of the disease and of the effect of steroids and cyclophosphamide. Dr Bamford referred to it on several occasions when giving his evidence and plainly had it in mind when expressing his opinions. Dr J W Schmidley, already mentioned, stated in the introduction to his chapter:

“Isolated vasculitis of the central nervous system (CNS) is rare, but not so rare that one or two cases are not encountered each year in large medical centres.”

Having considered the difficulties of diagnosis, Dr Schmidley added:

“The consequence of missing the diagnosis is the death of the patient, the consequence of delay in diagnosis is likely to be severe disability”.

Under the heading Therapy, Dr Schmidley stated:

“High dose prednisone plus cyclophosphamide is currently the treatment of choice (Calabreseet al. 1997). Some patients recover or stabilise on corticosteroid therapy alone, but more progress while only on corticosteroid therapy. The results of therapy are difficult to interpret because of the rarity of the disorder, so that even tertiary centres do not accumulate large numbers of patients; the difficulty of unequivocally establishing the diagnosis, other than by biopsy; and the inclusion of patients with the so-called benign form of CNS vasculitis, and of patients with diagnoses based only on angiography. Intravenous immunoglobulin has been administered with success a few times, but in poorly documented cases.”

In a chapter entitled “Neurology of the Inflammatory Connective Tissue Diseases” (from Major Problems in Neurology (Saunders 1999)), specifically mentioned by Professor Warlow in his report, Frans G I Jennekens and Louis Cater stated under the heading “Therapy and Outcome”:

“PACNS (Primary Angiitis of the Central Nervous System) is no longer considered as invariably fatal. Clinical experience suggests that it should be treated with high doses of corticosteroids or cyclophosphamide in combination with high-dose corticosteroids”…

The authors distinguished that condition from another, “a benign, monophasic form called benign angiopathy of the [central nervous system]”. They stated that “decisive for the distinction from PACNS is the clinical course, which is often sub-acute or acute in onset and monophasic (Calabreseet al. 1997). [PACNS on the other hand has a “fluctuating or progressive course”]. The neurological manifestations differ from those of PACNS in that non-focal changes such as cognitive deterioration, confusion and decreased consciousness are in the background or absent”.

In 1990, Dr Graeme J Hankey wrote an article entitled “Isolated Angiitis/Angiopathy of the Central Nervous System” (Cerebrovascular Disease, 1991, Volume 1). In the Abstract he stated:

“Until the last decade, the prognosis of isolated angiitis of the CNS was extremely poor. Most patients now survive and return to active lives. The major influence on outcome appears to have been the use of combination corticosteroid and cyclophosphamide therapy, although no randomized control trials have been undertaken”.

Under the heading “Natural History” Dr Hankey stated:

“Until the last decade, treatment was ineffective and the outcome was uniformly fatal. Hence, the natural history was accurately documented. The clinical course may be (1) acute, with rapid progression to stupor or coma, with a fatal outcome within 3 days to 6 weeks …: (2) it may wax and wane with spontaneous resolution of symptoms followed by stepwise progress …: (3) it may stabilize for prolonged time periods, or (4) it may progress insidiously over many months for up to 4 years… . Although early spontaneous improvement is not infrequent, 88% (37/42) of untreated patients died in the first year and no patients survived beyond 4 years (mean survival time 6 months, median 6 weeks, range 3 days to 45 months).”

Under the heading “Why do some patients die and others survive ?” Dr Hankey continued:

“The clinical course appears to have been influenced chiefly by the introduction of combination corticosteroid and cyclophosphamide treatment which was associated with considerable improvement or, at least, a stabilization of neurological signs over a variable period of follow-up in nearly all treated patients. However, selection bias is present as many of the early cases were described by pathologists and based on autopsy material.

Careful interpretation and cautious optimism are required therefore, as these reports involve very small sample sizes, non-randomized treatment and temporally inadequate follow-up of patients with a condition that may fluctuate clinically as part of its natural history”.

Dr Hankey also stated, under the heading “Treatment”:

“No controlled, randomized therapeutic trials exist because isolated angiitis of the CNS is rare and difficult to diagnose. A number of therapeutic agents have been tried, including aspirin, antibiotics, corticosteroids and cytototxic drugs. Only the latter two have been successful”.

Medical opinion is thus consistent in the view that, in its serious form, the illness is fatal without the intervention of drugs, that steroids and cyclophosphamide are the appropriate method of treatment and that they often achieve success. That this was a serious form of the disease was, on the evidence as it emerged, in my judgment the likely conclusion, had the judge addressed the question. It was the clear opinion of Dr Bamford, stated more than once in his evidence. It is confirmed by the seriousness with which those treating the claimant regarded the situation at 17:00 hrs on 27 April. Mr Havers accepted that the judge had to treat the case as a very serious example of the disease. It would be difficult to argue otherwise having regard to the medical literature and the disability, by stages, sustained.

Against this background, the judge should not have dismissed the literature in the summary way he did. In considering whether the achievement of stability was spontaneous or was caused by the drug therapy, the medical opinions emerging from the literature submitted to the judge require serious consideration. In the context of an illness which has fatal consequences in the absence of the administration of drugs, the maintenance of stability after the combination of steroids and cyclophosphamide has been administered cannot be ignored.

I turn to the judge’s reasoning at paragraphs 42 to 44. For the claimant, Mr Grace QC submits that the judge has in important respects misconstrued the evidence of Dr Bamford. Indeed, that is the main strand of his submission. Without considering the alleged misconstruction, however, the reasoning in those paragraphs cannot in my judgment stand. The “improvement” on 27 April mentioned by the judge is, on the evidence, better described as a stabilisation, a word used by the judge in paragraph 44. A serious deterioration in the claimant’s condition occurred on 27 April but, as the judge stated, “her condition had stabilised by 24:00 hours”. It does not, with respect, “follow” from the stabilisation achieved by that time that “the course the disease ran does not provide support for the contention that there would have been a more favourable outcome, and in particular the deterioration on 27 April would have been avoided, had cyclophosphamide been administered on 24 April”. That ignores the achievement, in the case of a normally fatal illness, of the maintenance of life and of stability once cyclophosphamide in combination with steroids had been administered. The judge has not mentioned, or it appears, taken into account the views consistently expressed in the medical literature, that, without treatment, the serious form of cerebral vasculitis is normally fatal in its consequences.

On the basis of the medical evidence and literature, it is entirely possible, to put it no higher, that the stability was achieved by the administration of cyclophosphamide with or without steroids. The fact that the drug could not have taken effect before midnight on 27 April does not mean that it could not have been effective after that in preventing further deterioration. It follows that the possibility that its administration on 24 April would have prevented the serious deterioration on 27 April cannot be ignored. The underlying neurological condition had been stable, as found by the judge, from 22 April until the serious deterioration on 27 April, and the presence of stability, even if without cyclophosphamide, at midnight on 27 April, does not complete the picture. The judge appears to have assumed that the stability achieved by that time was permanent. That cannot be assumed and the subsequent course of events must be taken into consideration when deciding whether the drugs had a beneficial effect and would have had a beneficial effect if administered earlier.

Dr Bamford expressed his opinion on the central point at issue in answer to the question: “If she had not received either steroids or cyclophosphamide, what do you think the outcome would have been ?” Dr Bamford stated: “I believe she would have continued to accrue neurological deficit and probably died, as happened in the pre-treatment era”. (Page 177).

When cross-examined as to what in his opinion had halted the disease process, Dr Bamford stated: “It’s the use of cyclophosphamide after the steroids. The treatment process is the combination”. He had stated earlier (p175) that the acute anti-inflammatory action was going to come from the steroids and that cyclophosphamide was much more about the suppression of the underlying disease. Asked whether there was evidence which pointed to the administration of cyclophosphamide as having been effective, Dr Bamford stated (p188):

“I think what points towards it is the subsequent stability of her course; the loss of the fluctuation; the loss of the accrual of new deficit. The reason I say that is because in the more aggressive ones, whilst I would expect steroids to have an anti-inflammatory response, they would be less likely to influence the underlying disease process – something which is more likely to be influenced by a drug like cyclophosphamide. This is why I was wanting to distinguish between an acute effect and a longer term sustained effect.”

When it was put to him that “no one actually knows for sure whether the cyclophosphamide improves the condition for sure”, Dr Bamford agreed. I have to say that I find it unsurprising that, in the context of medical knowledge, and a question which twice used the expression “for sure”, he was prepared to agree.

Dr Bamford was asked in detail about the comparable case he had treated. He stated (page 192):

“I have had one other patient who was not as ill but who was accruing multiple deficits where the same treatment stopped further deficits accruing within 48 hours.

Q. Right

A. Most of my other experience, as I think I said this morning, is based on more chronic cases”.

When, in re-examination, he was asked when the “favourable response” to the therapy commenced he stated: “I believe it commenced around late on 27 or early 28 as I said following which there was both stability and lack of accrual of further deficit”. Asked whether the improvement was because of the therapy or spontaneous, Dr Bamford stated (page 219):

“Step one is deterioration and the accrual of multiple focal deficits but particularly the fluctuation of conscious level, cognitive function and the things that have been highlighted in the references as the things that were poor prognostic factors and argued for a primary angiitis and not a benign angiopathy, and from the multi-focal nature of the damage”.

Dr Bamford later confirmed his view that this was not a benign case.

In that evidence, Dr Bamford appears to me to have been expressing an opinion which was relevant, coherent and cogent.

As to the time when the drugs are to likely to have taken effect after their administration, Dr Bamford put it, in the case of steroids as 3 to 5 days, and this was not challenged in cross-examination. As to the cyclophosphamide, he stated in his report, paragraph 7.6.1:

“Whilst there is a general acceptance in the medical literature that cyclophosphamide is the treatment of choice for aggressive cerebral vasculitis that has not responded to high dose steroids, I recognise that I am unable to find any significant body of literature which describes how rapidly one might expect the drug to bring an aggressive cerebral vasculitis under control. However, in my personal experience, some patients respond within a few hours and most patients seem to respond in less than 48 hours. This is consistent with Mrs Roughton’s case where there is no convincing evidence of any further neurological deterioration after she received the first dose of cyclophosphamide.”

In his evidence, Dr Bamford referred to the other patient he had “treated personally with this degree of aggressive presumed vasculitis”. He said that “the treatment appeared to have worked within 48 hours” but added “which bit of the treatment [steroids or cyclophosphamide], I don’t know”. He repeated (page 217) that it was “the treatment as a whole” which had to be considered. He agreed that the response on 27 April was not likely to have been due to cyclophosphamide.

Mr Havers relied (as did the judge) on a passage in cross-examination (pages 184-186):

“Q. Then we see that at 2100 hours – in fact, beginning, in truth, at 2000 hours and becoming apparent at 2100 hours – we have the first signs of improvement. For the transcript you nodded –

A.

I am sorry. I beg your pardon.

Q. And by 2400 hours we find that Mrs Roughton had improved to a Glasgow coma scale reading of, I think eleven. Is that right ?”

A (Pause) Yes. Eleven.

Q. If we go over the page to 298, [a reference to the neurological observations charts], we see that that is where she remained thereafter.

A. Until 30^th .

Q. Until 30 ---

A. Somewhere around there.

Q. Somewhere between 30^th and 1^st when she went up another notch.

A. I agree.

Q. So, within three hours then of the cyclophosphamide having been given at 1800 hours, there was the beginnings of improvement, and within six hours she had improved to the position at which she thereafter stabilised for several days.

A. That’s right, yes.

Q. Now, that is not a response within one to two days which you were talking about in your answer to Question 10? It is a response within a few hours.

A. It is.

Q. That being the case, it is exceedingly unlikely, is it not, that that response was due to the cyclophosphamide ?

A. I think, on balance, that response --- that response is not likely to be due to the cyclophosphamide..

Q. (Pause) Well, now, where do you say, if at all, we should assume that at some later stage the cyclophosphamide was having any effect?

A. When you give cyclophosphamide and steroids for vasculitis, there are two components to that treatment. One is the dampening down of inflammation, and the second, if you like, on the underlying disease process – to stop it recurring. (Pause) The observation that I have made in my report is that from that point where you have just gone through, a number of things stopped happening. Fluctuation, which had been prominent --- a prominent part of the illness, stopped, and there was no further accrual of neurological deficit after that time. Therefore, I concluded that the disease process had been brought under control. Because I can’t tell exactly when cyclophosphamide, if you like, kicked in, I don’t that. What I have observed is that that combination --- from that point onwards the combination of the treatments that she was given led to a stability in her condition, and no further --- lack of fluctuation and no further accrual of deficits.

Q. But you do not know that, do you?

A. I don’t know --- Sorry?

Q. You do not know that to have been the case.

A. What? Sorry. I don’t know what? Sorry.

Q. That there came a point when the cyclophosphamide kicked in.

A. No, what I said was that from that point the disease process, as I understand it, appeared to have been brought under control. (Pause) Now, at what point cyclophosphamide kicked in, and at what point the steroids were working, no, I ---

MR JUSTICE OWEN: Or whether the cyclophosphamide kicked in.

A.

I suppose, or whether --- or whether it did. I don’t know. (Pause) I can only observe what treatment she was given, and the apparent response to it. I don’t think there is anything there that allows me to disentangle the two.

MR HAVERS: Because if, as you have accepted, it was not --- I think you have accepted her improvement and stabilisation as from midnight on 27 was not due to the cyclophosphamide, then it must have been a spontaneous recovery and stabilisation, must it not?

A.

No. I’m sorry. I disagree with that. I mean, she’d been given five days of … (indistinguishable)… prednisolone by that point.

Q.

I see.

A.

What I’m saying – and I think you must just disentangle improvements on the evening of 27^th from stabilisation, because they’re two different things.

Q.

If we look over the page to 298, we know, because we can see from the chart on 298 that as from 2400 hours on 27^th her condition indeed stabilised.

A.

(Pause) Yes, I agree with that, that the stabilisation began around that time – in the sense that there is no further fluctuation and no accrual of further deficit.

Q.

And she remained stabilised thereafter.

A.

And she remained stabilised thereafter.

Q.

(Pause) In fact, a patient’s condition when a patient has cerebral vasculitis, can improve spontaneously without any treatment at all, can it not?

A.

If you are talking about cerebral vasculitis in toto, yes.”

[Dr Bamford had referred in his written report (7.3.1) to the distinction between “non-focal symptoms” and the “final cerebral damage”.]

Mr Havers relies in particular on two answers. First, it is claimed that when Dr Bamford stated that he did not think there was anything there that allowed him to disentangle “the two”, he was distinguishing between the treatment given and the apparent response to it. The second, when asked about spontaneous improvement, his answer, the last in the passage quoted, was: “If you are talking about cerebral vasculitis in toto, yes”.

As to the first point, I see great force in the submission of Mr Grace, that by his reference to “disentangling the two”, Dr Bamford was referring to the two drugs, the steroids and cyclophosphamide. His earlier long answer had referred to the combination of treatments, a point made elsewhere in his evidence, and referred to not being able to tell exactly when cyclophosphamide “kicked in”. Just before the statement relied upon, he had again referred, in an answer which was interrupted, that he did not know at what point cyclophosphamide kicked in. The reference to “treatment” and “response” appears to me to have been in effect in parenthesis and it was his difficulty in disentangling between the effect of the two drugs that Dr Bamford was repeating. I would have understood the answer in that way. Dr Bamford was not asked further questions to clarify the point.

As to the second point, Dr Bamford’s use of the expression “in toto” in my view deprives the answer of the sting relied on. Not surprisingly, he had been asked about the two forms the disease may take and it was not in issue that the benign form can improve spontaneously.

Of less importance, given the central issue, is the judge’s reliance on Dr Bamford’s answer to the question whether the steroids would have prevented the deterioration had they been given two days earlier that “it is unlikely because you are simply extrapolating from what happened”. The sequence of questioning was:

“Q. In that event, Dr Bamford, it is unlikely, is it not, that if steroids had been given intravenously in this case two days earlier than they were, they would have prevented the deterioration on 27^th April. That is unlikely, is it not.

A. If they had been given on their own ----

Q. It is unlikely?

A. It is unlikely because you are simply extrapolating from what happened.”

April 27^th was still within the bracket of 3 to 5 days when, on the evidence, steroids may take effect (22 April/27 April). Dr Bamford’s attempted answer was interrupted. While the matter is not free from doubt, what it appears to me the witness was conceding is that on the assumption that you can extrapolate from the period when there was no effect, there was no effect on the fifth day. It was unlikely to have been a concession that the steroids could not have had effect on the fifth day. No opportunity was given to the witness to clarify his answer. I add that Dr Bamford’s choice of the word “appeared”, when expressing his opinion on the comparable case should not in the circumstances of this case detract from his opinion. He had not claimed that certainty was possible.

Following a meeting between the neurological experts Dr Bamford and Professor Warlow on 1 October 2003, a series of answers had been recorded, incorporating, where there was disagreement, the opinion of Dr Bamford.

“Q6. Following the angiogram performed on 27 April 1998 when is it probable that the claimant’s clinical condition neurologically speaking (1) plateaued and (2) began to improve?

A.

In response to part 2, the experts agree that she began to improve within 24 hours. In response to part one, they also agree within 24 hours.

Q7. If the claimant establishes that it is probable that the claimant would have commenced on intravenous methylprednisolone on 20 April 1998 as opposed to 22 April 1998 and treated with cyclophosphamide on 24 April 1998 as opposed to 27 April 1998, is it probable that the claimant would have had a better outcome than she has had? Please give reasons for your answer.

A.

Dr Bamford is of the opinion that if treatment of methylprednisolone was started on 20 April 1998 and cyclophosphamide on 24 April 1998 then on the balance of probability the deterioration on the 27 April 1998 would not have occurred. The additional neurological damage accruing on 27 April 1998 would have been prevented and she would therefore have had a better outcome. The reason for his answer is that a review of the charts from the 27 April 1998 onwards shows that, following treatment, Mrs Roughton did not accrue any further focal neurological deficits and that her condition appears to have stabilised within 24 hours of the treatment with cyclophosphamide. He believes it was therefore probable that the same pattern would have occurred if that treatment (ie with methylprednisalone and cyclophosphamide) had been given as set out in the question.

[I have not included Professor Warlow’s answer because, subsequently, he became a committed ‘don’t know’.]

Q10. How soon after the commencement of treatment with cyclophosphamide would you expect to see an improvement in a patient’s condition?

A.

Both experts have discussed this with their colleagues. Professor Warlow’s opinion is that he would expect to see an improvement in a patient’s condition within a week or probably more. Dr Bamford’s opinion is that, he would say the speed of response to cyclophosphamide is variable. He agrees that in sub-acute or chronic cases the response maybe over days or longer but his opinion, based on small personal experience and discussion with colleagues who deal with systemic vasculitis, is that in very aggressive cases a response may be seen within 1 to 2 days.”

The word “improve” used in questions 6 and 10 is a misnomer in the sense that the court was concerned with the achievement of stability and the absence of further neurological deterioration. It is the claimed response to the drug therapy which is the important factor. Dr Bamford’s repeated use of word “response” in answer to question 10 is consistent with his oral evidence, though he did accept the word “improvement” in reply to a question which included that word, during re-examination (p217). The judge correctly used the word “stabilised” in paragraph 44 of his judgment and the expression “the course that the disease ran or its outcome” in paragraph 48.

Analysis of Dr Bamford’s evidence in my judgment reinforces the view that, with respect, it does not “follow” from the course the disease ran that there would not have been a more favourable outcome had cyclophosphamide been administered on 24 April. The evidence did not drive the judge to reach, as he thought it did, the conclusion he reached. The judge has not had regard to the achievement, after 27 April, of stability in a case of cerebral vasculitis where, on the evidence at it emerged at the trial, the outcome is normally fatal.

The judge did not make a clear finding as to whether this was a case of primary as distinct from benign vasculitis. The evidence that it was the more aggressive form appears to me, for reasons given earlier, to have been very strong. A conclusion that, because there was no deterioration after 27 April, necessarily, the therapy did not, and would not earlier, have worked, is not in my judgment tenable on the evidence. It could not be assumed that the stability achieved at midnight on 27 April was permanent. The stability between 22 April and early on 27 April did not prove permanent.

The question is whether, on the balance of probabilities, the earlier drug therapy postulated would have prevented the deterioration on 27 April. Whether the permanent stability achieved was spontaneous is obviously relevant to that question, it being agreed that stability as a result of drug therapy or stability achieved spontaneously are the only possibilities. The first question for this court is, however, whether it is able to decide that issue or whether it is necessary to remit the issue of causation for re-trial. Mr Grace submits that the court is an as good a position to assess the evidence as was the trial judge.

I have reluctantly come to the conclusion that remission is necessary:

a)

The judge has failed to focus on or to make a finding as to whether the primary or the benign form of the disease, as considered in the evidence and the literature, was present.

b)

The judge has failed to consider the significance of the maintenance of stability after 27 April and has wrongly confined his focus to the events of the last few hours of that day.

c)

The evidence of Dr Bamford is an important part of the claimant’s case and its assessment in the context of a trial, and with the correct issues in mind, is necessary.

Notwithstanding the detailed reference, and the sustained comment, I have thought it necessary to make upon the evidence and the judge’s approach to it, I am not able to hold that it is appropriate that this court should take upon itself the task of resolving the issue of causation. On that issue, and that issue alone, a reassessment of the evidence as a whole is required. The judge’s findings on other issues, which have not been the subject of challenge, will stand.

Evidence may be called. I am conscious that this gives the defendants a second opportunity to put forward a positive case which they could have, but did not, put forward at the trial on the issue the judge had identified. This could work hardship for the claimant but that possibility does not overcome the need for reassessment by a fact-finding tribunal.

To the extent indicated, I would allow this appeal

I agree that the issue of causation must be remitted for retrial, for the reasons which Pill LJ has given. I also agree with the observations of Hooper LJ (whose judgment I have had the benefit of reading in draft).

I agree with Pill LJ that the issue of causation should be remitted for a further hearing. The question which the judge had to resolve was whether the claimant had shown on the balance of probabilities that the substantial deterioration in the claimant’s condition which occurred on 27 April would not have occurred if the drugs had been administered earlier than they were: two days in the case of steroids and three days in the case of the cyclophosphamide. To resolve that issue, the judge had to decide whether, on the balance of probabilities, the drugs are generally effective to “treat” the form of vasculitis from which the claimant was suffering and if so in what period of time.

In deciding this issue the events of 27 April and thereafter were relevant (although not necessarily decisive). If the undisputed absence of any further deterioration after that date was due to the administration of cyclophosphamide on that day (alone or coupled with the administration of steroids), then that showed the effectiveness of the drugs. If the vasculitis was, on the balance of probabilities, of the kind which would cause death in the absence of the administration of the drugs, as Dr Bamford opined, then the absence of any further deterioration would have been caused by the drugs and would probably have been caused, so he thought, within less than 48 hours. Unfortunately the judge concentrated, as Pill LJ has explained, on the improvement by about midnight and not on the absence of any further deterioration. The improvement by midnight led the judge to conclude that the claimant’s condition was capable of spontaneous improvement and that the administration of cyclophosphamide on that day was not therefore shown to have had a beneficial effect. If he had concentrated on the absence of any further deterioration, his conclusions may well have been different.