Meiklejohn v St George's Healthcare NHS Trust

Originally two Defendants were named in this action. Proceedings against the second named Defendant were compromised some time ago. Thus I shall refer to the remaining first Defendant simply as the Defendant.

By this action the Claimant claims that he is the victim of clinical negligence in the diagnosis and treatment of a rare genetic disorder.

Mr Richard Booth, for the Claimant, in his extremely helpful opening skeleton argument, wrote:

“This is an unusual and medically complex case.”

Mr Alexander Hutton QC, for the Defendant, (whose appointment to the rank of Queen’s Counsel was made during the course of this case) in his equally helpful opening skeleton argument wrote:

“… the medicine in this case is relatively obscure and difficult …”

Having heard this case over the course of 8 days (excluding closing submissions) I wholeheartedly agree with both statements. I should pay tribute on behalf of all concerned to the glossary of medical terms prepared by Mr Hutton. I have used it to define certain terms in the course of this judgment

The Claimant was born on 20 January 1972. In 1993, at the age of 21, he was diagnosed with thrombocytopenia, macrocytic anaemia and hypocellular bone marrow. An overall diagnosis of aplastic anaemia (“AA”) was made. This case concerns decisions relating to diagnosis and treatment between March and May 2003

AA is a rare, potentially life-threatening failure of haemopoiesis (formation of blood cellular components). It is characterised by pancytopenia (reduction in the number of red and white blood cells and of platelets) and a hypocellular bone marrow. In the UK about 150 new cases are seen each year.

Most cases of AA are acquired. The mode of acquisition can be related to environmental triggers such as drug ingestion and exposure to viruses and toxins, but most cases are idiopathic.

In 2003, which is the year with which this case is concerned, some cases of AA were thought to be inherited and were known as inherited bone marrow failure syndromes. One such form is Fanconi’s anaemia. This case is concerned with another form, known as Dyskeratosis Congenita (“DC”). Patients have very short germline telomeres (a section of DNA). Short telomeres are associated with premature aging syndromes.

Telomerase is a ribonucleoprotein. It is an enzyme which adds DNA sequence repeats to one end of the DNA strands in the telomere regions.

Human telomerase consists of six molecules comprising two each of telomerase reverse transcriptase, (TERT) telomerase RNA (TERC) and dyskerin (DKC1). The “RNA” in telomerase RNA stands for ribonucleic acid.

This case is concerned with germline mutations in the gene encoding the RNA component of telomerase. This gene is referred to in the literature variously as hTR and TERC. It was discovered in about 2001.

This TERC mutation, in its inherited form, is an autosomal dominant trait, meaning that a single copy, inherited from either parent, is enough to cause this trait to appear. It is to be contrasted with autosomal recessive traits, where two copies of the mutation, one from each parent, are required.

Mutations in the DKC1 gene had been discovered before 2001 and were known to be linked to DC. Mutations in the TERT gene, also associated with DC, were discovered in 2005. These mutations are also autosomal dominant. Since then other genetic mutations connected to DC have been discovered. In all, at the time of this trial, 8 genetic mutations have been identified, 6 of them after 2003.

This case is in part concerned with the clinical signs of DC. Originally they comprised what has been referred to as the classic triad of symptoms comprising abnormal nails, reticular skin pigmentation and oral leucoplakia (white thickened patches). To what extent other clinical features may amount to diagnostic features is one of the issues in this case.

With advances in scientific understanding since 2003, it is now known that the TERC mutation is not necessarily always inherited. As will become clear in this case, in November 2005 tests performed on DNA, extracted from a sample of the Claimant’s blood, tested positive for the TERC mutation. However, subsequent tests performed upon the Claimant’s parents were negative, leading to the conclusion that the Claimant’s TERC mutation had arisen de novo and was not inherited. In consequence, the nomenclature has changed. Instead of referring to DC as a form of inherited AA, it is now described as a form of constitutional AA, to differentiate it from acquired AA. In this judgment I will use this form of nomenclature, even though it was not in use in 2003.

The treatment regimes for acquired AA and for (constitutional) DC are not necessarily the same.

Professor Judith Marsh is one of the Country’s leading experts in AA. As she describes in her witness statement, in March 2003 she was Reader in Haematology at St George’s Hospital Medical School in the Department of Haematology. The Director was Professor Gordon-Smith, whom she describes as “a leading authority in AA”. In November 2003 she was herself appointed Professor of Clinical Haematology at St George’s Hospital. I shall refer to her as Professor Marsh throughout this judgment, even though the principal events occurred whilst she was still Dr Marsh. The Claimant also refers to Judith Marsh by the title “Professor” when describing all of his dealing with her from his first contact with her in March 2003, and when quoting from his evidence, if he refers to her as “Professor” I shall do likewise, even if it is technically inaccurate.

This case centres upon a diagnosis made in March 2003 by Professor Marsh that the Claimant was suffering from acquired AA. The diagnosis arose in this way.

An initial diagnosis of AA was made in about 1993 when the Claimant was aged 21. A watch and wait policy was adopted.

In December 2002 the Claimant was referred to Professor Marsh at St George’s Hospital. It is acknowledged that St George’s Hospital was (and is) a national tertiary referral centre for AA. On 25 March 2003 he was seen by Professor Marsh. He was examined and a history taken. There is a dispute concerning the nature and extent of those processes. At the end of the consultation the Claimant was told that the diagnosis was acquired AA (hereafter simply AA). It was considered to be non-severe AA as opposed to severe AA. Standard treatment for non-severe AA is with Anti Lymphocyte Globulin (ALG). This requires admission as an in patient, which occurred in May 2003. A 5 day course of ALG was begun on 7 May 2003. One of the side effects of the administration of ALG is serum sickness. To help prevent this, a dose of the corticosteroid Prednisolone was administered.

Administration of Prednisolone itself carries certain risks. A rare side effect is avascular necrosis (AVN). The Claimant was not informed of the possibility of the manifestation of this side effect before Prednisolone was administered.

The Claimant did develop AVN of both hips. This was diagnosed on 24 June 2005. He underwent bilateral hip replacements.

Treatment for DC is often by administration of Oxymetholone, which is a synthetic hormone. It is also treatment for AA alternative to treatment by ALG. In issue is whether ALG is an appropriate treatment for DC.

After the first course of ALG treatment had been administered, the Claimant’s treatment was altered. On 17 November 2003, the Claimant saw Professor Marsh again. In her witness statement Professor Marsh says that there had been a partial response to the ALG. She says the Claimant was not keen on another course of ALG. The upshot was that the Claimant’s treatment was altered to administration of Oxymetholone.

When the Claimant was seen by Professor Marsh in March 2003, blood samples were taken. One of these was sent to Professor Inderjeet Dokal. He is probably the world’s foremost expert in DC which is, as explained above, a form of constitutional AA. There are many issues which fall to be resolved concerning the taking of this sample of blood and the purpose for which it was sent to Professor Dokal.

It was not until 11 November 2005 that the blood sample sent in 2003 was analysed and there was found the mutation of the TERC gene referred to in paragraph 16 which led to a diagnosis of DC. The results were sent to Professor Marsh on 17 November 2005.

The Claimant’s complaints may be summarized thus:

I have already referred to the Claimant and Professor Marsh.

The Claimant called as a factual witness Mrs Katherine Adams. She accompanied the Claimant to the consultation with Professor Marsh on 25 March 2003. She has been a nurse since 1995 and is presently a Senior Sister in the Accident and Emergency Department of Homerton Hospital, a position she has held for upwards of 6 years. She described the Claimant as her best friend and explained that this was why she had gone with him to the consultation with Professor Marsh.

Expert evidence was given on behalf of the Claimant by Professor Eva Guinan who, amongst other titles, is Associate Professor of Pediatrics at the Harvard Medical School based at the Dana-Farber Cancer Institute in Boston, USA. The reason why the Claimant felt it necessary to go abroad to seek an expert is simply because in the narrow field of medicine with which this case is concerned, there is no-one in the UK who is not closely connected with Professor Marsh.

On behalf of the Defendant I heard from Professor Marsh. In oral evidence she explained that she had become interested in AA whilst she was a Registrar at Hammersmith Hospital. She spent 3 years doing research and then moved to St George’s Hospital to continue her interest in AA. She said that she sees about 50 new patients with AA each year, out of about 150 newly diagnosed patients in the whole of the UK.

Factual evidence was given on her behalf by Professor Dokal, who I have already mentioned. In March 2003 he was Reader/Honorary Senior Lecturer in Haematology at Imperial College and Hammersmith and St Mary’s Hospitals. He became Professor and Honorary Consultant in October 2003. In September 2006 he took up a post at Barts and The London NHS Trust which seems to comprise a number of titles including Chair of Child Health. In 1995 he established the international Dyskeratosis Congenita Registry. He describes this in his CV at page 9 of his witness statement dated 14 April 2010. He says that “the main research aim is to understand the pathophysiology of aplastic anaemia and related disorders with the long term aim of developing new treatments for patients lacking compatible haemopoietic stem cell donors”.

Professor Edward Colin Gordon-Smith was, from January 1997 until his retirement in September 2003, the Director of the Department of Haematology at St George’s Hospital Medical School. Dr Marsh was, until her promotion, part of his team. His evidence was directed to the standard practice of the Hospital in 2003 concerning the taking of blood samples. He did not ever meet the Claimant.

Expert evidence on behalf of the Defendant was given by Dr Jamie Durrell Cavanagh, who was appointed Honorary Professor in September 2011. He holds the post of Consultant Haematologist at Barts and the London NHS Trust and is the Clinical Lead in Haemato-Oncology. As he explained in his report dated 12 September 2010, he sees adults with AA in both the acquired and congenital forms.

The extreme narrowness of the field of medicine with which this case is concerned is demonstrated by this curious feature of the factual circumstances concerning the Claimant’s treatment. As is obvious, he was initially treated by Professor Marsh. He was then referred to Professor Dokal. Dr Cavanagh says this at p 3 of his report:

“As a point of note, Professor Dokal has recently referred Mr Meiklejohn to my clinic since the prospect of a bone marrow transplant as part of his case may be appropriate in the future. However, I have not yet seen him personally, and I do not consider there is any conflict with my duty to the Court.”

That is a proposition with which Mr Booth took issue and with which I must deal in due course.

It is necessary to determine what features are sufficiently indicative of DC such that Professor Marsh ought to have suspected DC. Only following such determination can the competence or otherwise of the examination of the Claimant on 25 March 2003 be properly judged. In this context, one must have regard to physical features observable on competent examination taken together with information obtained upon the taking of a competent clinical history.

The typical physical features of DC have been referred to in evidence as the classic triad. They are:

Leucoplakia refers to one or more thickened white patches on a mucous membrane, which in the case of DC means the mouth and tongue, which cannot be rubbed off.

Nail dystrophy seems to refer to a range of abnormalities in the nails including regression, discolouration and ridging.

Reticulate skin pigmentation refers to a pattern of darker skin pigmentation in a networked pattern. However, Professor Dokal said in evidence that he now referred to abnormal skin pigmentation, in recognition of the fact that physical features such as dark spotting were also within the classic triad

The Claimant’s case is that there are other subtle features which may be present in the absence of any of the classic triad. He says that some of these features were present in his case. However, the Claimant’s case is not that Professor Marsh ought to have reached a working diagnosis of Constitutional AA. Instead the Claimant says that there were sufficient clinical features present, both in the form of physical findings and clues to be gleaned from the taking of a proper clinical history, to raise the index of suspicion to a level such that Professor Marsh should have made, or caused to be made, further investigations, which in this case means asking Professor Dokal to expedite his work on the Claimant’s blood sample so that the results which were in fact made available in November 2005 would have been made available shortly after the samples were sent. This, it is argued on behalf of the Claimant, would have resulted in a different treatment regime being instituted such that the Claimant would not have developed AVN.

The first issues for me to determine are factual and concern the consultation on 25 March 2003. What was there to be seen upon competent clinical examination of the Claimant? What was there to be learned from the taking of a competent clinical history?

The evidence of what occurred when the Claimant was seen by Professor Marsh comes from the Claimant, his witness Mrs Katherine Adams, Professor Marsh and from the contemporaneous documents. Reliance is also placed upon what was seen when the Claimant was clinically examined on subsequent occasions.

The Claimant’s recollection of his first meeting with Professor Marsh is contained within his witness statement. At paragraph 6 he explains that Dr Amos, a consultant haematologist at the Homerton Hospital had diagnosed the Claimant with AA and had referred the Claimant “to Professor Judith Marsh … for specialist treatment, …”.

In paragraph 7 he says this:

“I saw Professor Marsh on 25 March 2003. … Professor Marsh took some details of my past history and examined me for the signs of AA (eyes, pallor, blood pressure and respiratory sounds) but did not perform a full body examination. My fingernails and toe nails were ridged at the time, as they always have been, and I was very much greyer haired than I had been as a teenager. She ordered more comprehensive blood tests and a bone marrow biopsy. Professor Marsh suggested a probable diagnosis of acquired AA and recommended that, in due course, I undergo Anti-Lymphocyte Globulin (ALG) as the treatment for my condition. I was not advised that there was any other possible form of treatment …”.

In oral evidence in chief he said that the consultation with Professor Marsh had lasted about 15 to 20 minutes with the same amount of time being spent on the blood work.

In cross examination he accepted that the consultation with Professor Marsh may have been longer than 15 to 20 minutes. It was put to him that Professor Marsh had said that her standard practice is for a consultation to last for an hour to an hour and a half. The Claimant said that it did not seem that long.

He agreed in cross examination that there had been a detailed discussion about the way forward in terms of treatment and diagnosis and that there had been a detailed and involved discussion concerning his clinical history, including previous blood related problems and a serious bladder infection in 1999. He added that there had been several episodes of bladder infection and a hospital admission for epididymitis affecting both testicles.

He agreed also that Professor Marsh had asked him about his family with a view to finding a bone marrow transplant donor and that she had also suggested that the Claimant may have Fanconi’s anaemia. He denied that he had been told that this was an inherited condition. He agreed that he was aware that blood would be required to test for Fanconi’s anaemia, but he denied that he had been told some of his blood would be used for research purposes. I shall return to that topic later.

In oral evidence in chief he referred to photographs exhibited to his supplemental witness statement dated 28 May 2010 and explained that they had been taken sometime earlier in May 2010. The supplemental statement was made, as the Claimant explains in paragraph 3 of it, “to demonstrate photographically the abnormalities of my hair, skin and nails (fingers and toes) that are present now and that were present in March 2003”.

In cross examination, he gave these particulars of what the photographs show. He dealt with this aspect of his evidence in 2 parts, because on the second day of the trial, after he had nominally concluded his evidence, better copies of the photographs were produced, along with electronic images on a data stick. In the supplemental witness statement, the photographs were numbered 1 through to 14, but also bore page numbers from page 5 to page 18. I shall attempt to give both references.

Of the photographs generally, the Claimant said that there had been no dramatic change in his appearance between 2003 when he saw Professor Marsh, and 2010 when the photographs were taken.

The witness statement of Mrs Adams is dated 19 May 2010. She said within it:

At paragraphs 21 to 24 of her statement Mrs Adams describes the Claimant’s physical features as noted by her over the years she has known him and then says this at paragraph 25: “When Richard was subsequently diagnosed with DKC and we learned about it, even with my limited experience I was able to easily pinpoint these signs that had been previously evident”.

In oral evidence she confirmed that the contents of her statement were true and repeated that the meeting with Professor Marsh lasted “for 10 minutes or so” and added that blood samples had also been taken after the meeting, as well as before.

In cross examination it was suggested to her that given the passage of time, her recollection of the meeting with Professor Marsh could not be precise. Mrs Adams replied “I recall it very well. I went with my best friend to receive what we thought would be bad news.” She was reminded that the Claimant had said that he recalled some discussion of Fanconi’s Anaemia. She said that she did not recall any discussion about inherited conditions.

Professor Marsh dealt with her examination of the Claimant in her witness statement dated 9 July 2010 by reference to her standard practice at the time:

Concerning the examination of the Claimant, she said this:

In oral evidence she said that in 2003 she saw about 50 AA patients a year, which represented about one third of all AA patients in the UK. She was asked about her understanding in March 2003 of patients who appeared to present with AA but who in fact had DC. She said this:

“It was recognised that the most common form of DC was the classic form with the triad of symptoms. I was aware of new research just starting to identify other genes that may be involved. This was being conducted by Professor Dokal and also in the USA. I was also aware at the time of a report from Dokal where he had screened a number of patients with idiopathic DC, where 2 of the 17 patients had the genetic mutation but not the classic symptoms. This was a new finding, in just 2 patients. Its significance was not known then. More research was required.”

She was asked specifically of her knowledge “of things like receding hair and greying and thinning of hair” as amounting to “subtle signs” of DC. She said it was an evolving field and that she was not aware of any research showing that such subtle signs in a patient with apparent AA could be DC.

In cross examination she was asked if, in the Claimant’s case, she had a raised index of suspicion that he may have DC. She said she did not when she saw him. She was asked this in the context of the blood sample to be sent to Professor Dokal, the proposition being that this was indicative of a suspicion that the Claimant had DC. She denied that, saying that “we routinely sent off samples for Professor Dokal’s DC research. Nothing in the Claimant or his history made me suspect he may have the inherited form of AA”.

Certain features of the Claimant’s clinical history were put to Professor Marsh, namely his long term macrocytosis and history of unexplained urinary tract infections. Professor Marsh said that macrocytosis was a very common feature of AA and that neither the duration nor severity of the condition assisted in determining if the patient had the inherited form of AA. She repeated later in her cross examination that there were no clinical grounds in 2003 to cause her to suspect that the Claimant had DC. She agreed that AA is a diagnosis of exclusion and that her assumption was that patients walking through her door have AA, but she denied that this was a dangerous practice, explaining that she looked for clinical signs of DC.

She was pressed further about the urinary tract infections and the hospital admission in 1999 for epididymitis. It was put to her that, with the benefit of hindsight, she ought to have taken more notice. She denied that proposition and said: “No. There was no doubt in my mind that this was a barn door case of acquired AA. A history of urinary tract infections is not specific to DC”.

She was taken to a variety of papers showing that from about 1996, patients with DC had been found to be exhibiting symptoms outside those represented by the classic triad. Specifically, she disagreed with the proposition that nail ridging amounted to nail dystrophy, and said that there must be other signs of nail dystrophy in addition. She said, of her examination of the Claimant, that she had looked at his nails, making the point that whenever she saw a new patient with AA, she looked for signs of Fanconi anaemia and X-linked DC, and thus she always looked for the classic triad. She was adamant that signs such as dry skin, grey hair, a receding hair line were non specific findings. She said she did not observe any brown spots on the Claimant’s back, and did not consider a history of pancytopenia and macrocytosis to be of significance in considering a differential diagnosis of DC.

In re-examination she was taken to a paper by Professor Dokal and his colleague Dr Vulliamy entitled “Dyskeratosis congenita: its link to telomerase and Aplastic anaemia” published in December 2003, where the main emphasis was still on the classic triad of symptoms with the observation that “a variety of other (dental, gastrointestinal, genitourinary, hair greying/loss, immunological, neurological, ophthalmic, pulmonary and skeletal) abnormalities have also been reported”. Professor Marsh said that in March 2003 she would not have been alive to these milder manifestations and would not and did not suspect DC in March 2003. It was only when the Claimant was diagnosed with AVN that she began to consider the possibility of DC.

In answer to questions from me she said that even in the absence of any of the classic triad, her practice in 2003 was to look for less common signs of DC. She said “I start the examination as soon as the patient walks into the room. In this case, the only less common sign was grey hair and hair loss. So what, in a 31 year old male?”

It is relevant to consider what Professor Dokal noted upon examination of the Claimant in February 2006 and on subsequent occasions.

In his witness statement dated 14 April 2010 Professor Dokal said that he had seen the Claimant on 16 February 2006 and said this at paragraph 6: “He still had (and has) normal nails and skin. Therefore clinically it would have been difficult to say he has DC”. He referred to a recent letter dated 16 January 2010 and said: “I reported that examination of the nails was essentially normal then as was the skin. This makes it very likely that the nails and the skin were normal in 2003”.

Professor Dokal recorded his findings upon examination of the Claimant on 16 February 2006 in his letter dated 6 March 2006, to which I have already referred. There are also relevant documents to which Professor Dokal was referred when giving oral evidence. His clinical notes made at the time of his examination are at CB/14/Ham 2.4. He noted “Imp[ression]. V[ery] little in way of muco cutaneous features”

At CB/22/GPU 3.43 there is a letter dated 5 August 2010 from Professor Dokal in which he wrote: “His hair line seems to be receding more than his previous visit and I noticed some increased pigmentation around the forehead. … Examination of his hand and toe nails looked reasonable. Although interestingly for the first time I have noticed some discolouration of his big toe nails.” Professor Dokal said in evidence that the only significant change from his previous impression of “v[ery] little in way of muco cutaneous features” was the discolouration of the big toe.

In a letter dated 20 January 2011 (CB/22/GPU 3.48) Professor Dokal wrote: “His hand nails essentially looked normal but perhaps have a slight brittle look to them. His toe nails on the whole look relatively normal. The right big toe is slightly discoloured. Examination of the skin is not showing any obvious major abnormalities. Examination of the tongue was normal …”. Of his findings recorded in that letter Professor Dokal said that the only change was that the nails looked softer and more brittle.

Professor Dokal saw the Claimant again in May 2011 and recorded his findings in a letter dictated the same day (CB/22/GPU 3.55). He recorded pigmentation changes around the forehead and again noted the discolouration of the big toe nails.

Finally, in a letter dated 13 October 2011 (CB/22/GPU 3.66) he recorded his findings upon examination on 11 October 2011. He wrote: “As before he has some grey hair on his scalp and he has a receding hair line. Examination of the tongue was normal … hand nails showed no obvious nail dystrophy. As before, he has some discolouration of the big toe nails. Skin was again largely normal. There are some questionable pigmentary changes on the back.” Professor Dokal explained in oral evidence that he thought he had seen something on the Claimant’s back.

Professor Dokal was asked directly whether the clinical appearance of the Claimant in February 2006 alerted him to the possibility that the Claimant had DC. He said the only one consistent feature was grey hair, but that this was not significant. He said “it is still now not easy to see the triad”. He was asked if the symptoms were progressive. He said that in cases of the DKC1 mutation they are usually progressive, but that the number of muco cutaneous features is far less in TERC and TERT mutations, adding that he had put this in a recent paper in 2011.

In cross examination on this issue, he was taken to his letter dated 6 March 2006 and asked if on the basis of his findings, the Claimant would have fallen into the constitutional AA category. He said “I would probably have classified this as constitutional AA but not other clinicians. Even for me this is borderline. Possibly I might have done but I might not have done”.

Dr Cavanagh’s expert report is dated 12 September 2010. As I have already said, at page 3 of his report he wrote: “As a point of note, Professor Dokal has recently referred Mr Meiklejohn to my clinic since the prospect of a bone marrow transplant as part of his care may be appropriate in the future. However, I have not yet seen him personally and I do not consider there is any conflict with my duty to the Court.”

By the time of the discussion between the experts on 7 November 2011, Dr Cavanagh had seen the Claimant. He referred to this fact in answering Q15(c) in the agenda when he said this: “… we met … on November 2^nd 2011. He has none of the three classic muco-cutaneous features of DC. He has thin hair and premature greying of the hair (but reports that there is a family history of such on his mother’s side). I could not see any abnormal skin pigmentation of any sort on the trunk although he does have some abnormal ‘eczematous-appearing’ skin on the lower legs along with purpura. I did not feel that he has abnormal nails. The only finding is of minimal ridging, certainly compatible with what is seen in the normal population. Indeed, the degree of ridging is less than my own. I would not have suspected DC on clinical grounds alone (over eight years later, over which time DC-related features would be expected to be more evident).”

It is also relevant to note the response of the experts to Q15(h) of the agenda. The question was in the form of this proposition: “That the findings present on clinical history and examination of the Claimant in February 2006 were also likely to be present in March 2003”. Dr Cavanagh replied: “Not true. It is well known that the somatic features of DC develop over time and often appear well after detection of bone marrow failure.” Professor Guinan wrote: “Agreed. However, the history of marrow failure and the history of hair greying would have been unchanged, at the least. It is extremely difficult to understand what skin and nail findings were present when although to me suggestive that they have may have been present, albeit certainly not classical, at times antedating 2003 (see testimony of nurse Kathy Adams).” Neither expert was asked about these answers in oral evidence.

The preponderance of the evidence supports the proposition that there cannot, in 2003, have been any more to see than there was in 2006. I have to determine if there was less.

The Claimant’s pleaded case is that Professor Marsh ought to have suspected that the Claimant had DC. It is set out in paragraphs 13A and 44(bb3) of the Amended Particulars of Claim. It is alleged that Professor Marsh failed to note that the Claimant had early greying of the hair, a receding hair line, thinning poor quality nails, dry skin, odd pigmentation on the back and had had recurrent urinary tract complaints without positive cultures.

I come to the following conclusions on the preponderance of the evidence.

I have referred to the view of Professor Dokal, but he was not called to give evidence in an expert capacity.

I have already introduced Professor Eva Guinan, albeit only briefly, who gave expert evidence on behalf of the Claimant. She is a truly remarkable person who gave evidence over a live visual link from the Harvard Medical School beginning at what for her was 5.30 am in the morning, before going on to perform a day of clinical duties.

She expanded upon her CV, explaining that she was a bone marrow doctor with an interest in bone marrow failure. In 2003 her clinical commitments comprised 3 days per week on what she described as patient work, which included supervising the majority of bone marrow patients as well. Since 2003, Professor Guinan said she has reduced her clinical work in order to do more research.

She developed an interest in AA as a resident and at the same time became interested in transplants. At her busiest she was seeing an AA patient every other week, but that included established patients as well as new patients. She said that in 2003, the aggregate number of patients she saw in a year was 25, but pointed out that if a patient was an in-patient, she would see that patient every day. The age range of her patients was 1 to 50 with the majority aged between 10 and 30. She said she did not have a particularly extensive experience of DC.

She considered that Professor Marsh was one of the top 20 AA experts in the world, and put herself in the same category. She said she was aware of Professor Dokal, whom she described as a “very well regarded expert in the area of DC.” Of Dr Cavanagh she said she had not been aware of him before her involvement in this case.

Professor Guinan drew attention to the fact that the Claimant’s hair had been grey since age 13 – a feature noted by Professor Dokal - and also attached weight to the Claimant’s macrocytosis, describing the large size of the red cells as “remarkable”.

There was much examination of numerous medical papers with a view to discerning a growing stream of knowledge showing that there are patients with DC who do not exhibit the classic triad of physical features. However, even in 2009, in a paper co-authored by Professor Dokal (D/45) this seemed to be the position:

“… we need to move away from the very rigid diagnostic criteria of the presence of the mucocutaneous triad of skin pigmentation nail dystrophy and oral leucoplakia. In the absence of an internationally accepted diagnosis the best criteria still seems to be that of Vulliamy et al (2006) i.e. the presentation of one or more of the mucucutaneous features in combination with hypoplastic bone marrow and two or more of the other somatic features known to occur in DC (such as hair loss, abnormal dentition, malignancy, pulmonary disease, short stature, liver disease, developmental delay etc.).”

Professor Guinan has the personal and professional advantage of working in what appears to be an extremely well funded hospital in the USA with a patient load that seems to be rather lower than that in any NHS hospital. But this is actually a disadvantage in the context of assessing her opinion evidence by reference to the standard of care to be expected of a clinician working in an NHS hospital in 2003. As she said in evidence, her only experience of working in England was as a doctor in the department of obstetrics and gynaecology at St Thomas’ Hospital. Mr Hutton mistakenly put it to Professor Guinan that this was for a limited period of 6 months. She corrected him and said it was in fact only 6 weeks, observing that “if it had been 6 months I would still be recovering from it”. She also suffers the clear disadvantage of never having examined the Claimant herself.

Professor Guinan was able to point to each of the relevant features identified by her as raising a suspicion of DC, such that, in her opinion, it could not have been excluded as a diagnosis. That being so, there should, in her opinion, have been what she described as a “nuanced” discussion concerning treatment options. The basic premise appears to be that both ALG and Oxymetholone would be considered as treatment options since both AA and DC were potential diagnoses.

I turn next to the evidence of Dr Cavanagh. I shall use the title “Dr” despite his elevation to the honorary chair in September 2011.

His report is dated 12 September 2010. It is commendably brief and to the point. There was nothing in the presentation of the Claimant in 2003, either physically or by reference to his clinical history, to put Professor Marsh on the alert that he may be suffering from DC.

It is agreed that DC is more commonly diagnosed in children than adults. Dr Cavanagh states that the median age of presentation is 7, whilst Professor Guinan’s experience in the USA is of a median age at presentation of between 16 and 18.

In oral evidence he expanded upon his clinical experience. He said he had first met Professor Marsh when she was a consultant and he was her Registrar. He worked with her at St George’s Hospital for less than a year. Whilst there, he saw AA patients in his clinic and as in-patients.

In his current post, his department is the one of the largest clinical haematology units in the UK seeing AA patients from a referral population of 2.5 million. It is a tertiary referral centre for AA, serving a different population than St George’s although St George’s is also a national referral centre.

In his current post he said he saw a selection of malignant cases such as AA together with some cases involving benign bone marrow failure syndrome

He said he was a specialist in the management of certain haematology cases including bone marrow failure cases and as such had an interest in transplantation. In connection with any suggestion that his area of interest and expertise was in transplants for persons suffering from malignant disease rather than in AA he said he was qualified to give evidence of practice at a tertiary referral centre for AA. He made the point that he was a member of the committee which had written the 2009 guidelines, observing that “there was a reason for that”.

In cross examination Dr Cavanagh was subjected to scathing criticism of his role in this case. It was put to him in terms that “your conduct in this litigation has been a disgrace to your profession”. The foundations for this extremely serious assertion are:

I absolutely and categorically reject those assertions:

I have to say I was very impressed with Dr Cavanagh. He struck me as a solid sensible clinician who did have an appropriate expertise in AA such that his evidence was of real assistance to me in this case. I thought there was real force in his evidence contrasting the positions in the UK and in the USA, and also the status of Professors Guinan and Dokal contrasted with others.

When being asked about the criticisms of Professor Marsh’s failure to record negative findings in her clinical notes he said of the record “it seems to me to be a perfectly adequate record of examination. Professor Guinan is speaking from the American point of view. All possibly relevant negatives are recorded. This springs from the medico-legal perspective. And they have more time. They may see 4 patients in a clinic. Professor Marsh and myself see between 12 and 20. They record all potential negatives. I don’t and I don’t see why Professor Marsh should”.

On the critical issue of whether Professor Marsh should have suspected DC, he said she should not. He said: “even going forward 3 years to the 2006 diagnostic criteria [a reference to Vulliamy et al] the Claimant did not fulfil those diagnostic criteria. Professors Guinan and Dokal are super experts. No one in the world knows more [about DC] than Professor Dokal. It is not appropriate to compare Professor Marsh with Professors Dokal and Guinan because they are dedicated to inherited bone marrow failures – Guinan for Fanconi and Dokal for DC. Professor Marsh is the pre-eminent AA doctor. I can see no reason why in March 2003 she should have made a diagnosis of DC. Being on the lookout for mild phenotypes becomes ridiculous. Is one freckle enough? The best diagnostic definition is [Vulliamy et al in] 2006. In 2003, you had to have all 3 [of the classic triad]”.

He was pressed further on this in cross examination, being reminded that in 2006 Professor Dokal had considered that the Claimant may fall into the constitutional AA category on the basis of clinical findings alone, such that if those features were present in 2003, Professor Marsh ought to have considered DC. Dr Cavanagh was adamant on this issue. He said this: “No. Professor Dokal has dedicated his professional career to constitutional AA. He was picking up very minor features that no-one else would. He is in a super niche area in DC. Professor Marsh is not. The practices of Professor Marsh and myself are much closer to each other than that of Professor Guinan. She specialises in children and Fanconi, and she is super niche in that area.”

He was clear in his view that, as an AA clinician, features such as macrocytosis and pancytopenia were not diagnostic of DC.

The clear impression which I got is that the papers dealing with symptoms of DC other than the classic triad were retrospective studies of patients who either had been related to a patient who had exhibited the classic triad or who had been diagnosed with DC as a result of genetic testing. Much time was spent in considering papers dealing with a family in Iowa, USA. However, as Dr Cavanagh pointed out, the index case in the Iowa family had the classical presentation.

In fairness to the Claimant, his case, I remind myself, is not that a primary diagnosis should have been made. It is merely that the index of suspicion should have been raised to the relevant level.

I was left with the overwhelming impression that Professor Guinan had approached this case by reference to standards in the USA rather then in the UK, and that, try as she might, she had been unable to consider this case from a prospective basis, but instead has looked at it in retrospect. We all know now that the Claimant has DC. In retrospect it can be seen that some features exhibited by the Claimant are consistent with that diagnosis. But what conclusions should have been drawn by a clinician who did not have the luxury of knowing that the Claimant had DC? I was impressed with the evidence of Dr Cavanagh on this issue. I felt that he more accurately directed his mind to the difficult analysis of what an AA specialist in the UK would have concluded in the light of my findings concerning what there was to discover in March 2003.

On that basis, in this case, I am satisfied that there was simply not enough in the Claimant’s physical presentation or history to put even a clinician of Professor Marsh’s standing on the alert.

In this respect it is, in my judgment, of relevance that in 2009 the “Guidelines for the diagnosis and management of aplastic anaemia” were published. These replaced guidelines which had been published in 2003. Professor Marsh was the leader of both of the groups who had devised the guidelines. Dr Cavanagh, Professor Dokal and Professor Gordon-Smith were members of the 2009 group. The position seems to be that even by reference to these recent guidelines, the Claimant would not have been diagnosed with DC, much less in 2003. Whilst on behalf of the Claimant it was sought to establish that both sets of guidelines were not designed to apply to world experts such as Professor Marsh, it seems to me that this is putting the bar too high.

I must nevertheless deal with the position concerning the blood sample sent to Professor Dokal.

As I have already said, the Claimant first met Professor Marsh on 25 March 2003. In addition to the consultation itself, samples of the Claimant’s blood were taken. The Claimant’s case is:

The first issue is that of knowledge and consent.

It is not in dispute that a sample of the Claimant’s blood was in fact sent to Professor Dokal. The sample appears to have been sent on about 26 March 2003 and appears to have arrived at Professor Dokal’s laboratory soon after that.

There are two main issues concerning the taking of the sample of the Claimant’s blood which was sent to Professor Dokal. The first is that of informed consent. The second is the purpose for which the sample was taken.

Professor Marsh says that, in March 2003, it was her practice, when seeing a patient such as the Claimant, to send to Professor Dokal a sample of the patient’s blood, she says for research purposes.

It is agreed that the Claimant did not give his written consent to a sample of his blood being taken and sent to Professor Dokal. Professor Marsh says that she obtained his verbal consent for a sample to be sent for research purposes. The Claimant says he knew nothing about any blood being sent to Professor Dokal for any purpose. Had he known, he says he would have asked about the research with the result that he would have wanted to consider treatment options. At paragraphs 61 and 63 of his witness statement he said:

“At no point did Professor Marsh explain to me that she had taken a blood test for either Fanconi Anaemia or DKC.

“I am also certain that on no occasion did Professor Marsh explain to me that I might have blood or any other tissue samples used for research purposes … and I did not give consent for such purposes either written or verbal.”

Mrs Adams also says that no mention of research was made. She put it in this way in her witness statement at paragraph 14:

“In addition Dr Marsh never mentioned research or the possibility of research, either in a generic context, in that St George’s Hospital carried out research for Aplastic Anaemia, or in relation to any specific research project. There is no doubt in my mind that Dr Marsh did not mention research, as my ears would have pricked up very significantly if she had, as would Richard’s.”

In cross examination it was put to Mrs Adams that Professor Marsh had said that a sample of blood would be used for research. Ms Adams denied this, saying: “As a nurse I am very aware of research and I would have been alert to the word research”.

Professor Gordon-Smith was called to deal with what he describes in his witness statement dated July 2010 as the “standard practice” concerning the taking of “routine blood samples” which existed at St George’s Hospital in March 2003 when he was Director of the Department of Haematology.

In his witness statement he said:

In oral evidence he accepted that written consent for blood to be submitted for research should have been obtained, as did Professor Marsh.

In cross examination he agreed that it had been his practice to send selected blood samples to Professor Dokal for diagnosis and management, but added that he knew he would not get the results soon and treatment was not held up. He said “I could ‘phone up and ask for a hurry up, but it did not always work”.

I am satisfied that the Claimant and Mrs Adams are mistaken about the duration of the consultation. It must have been much closer to the average time of 60 minutes stated by Professor Marsh than the 10 or 20 minutes of Mrs Adams and the Claimant. Mrs Adams appears confused about the taking of blood samples – before the consultation in her witness statement, both before and after in oral evidence. She recalls no mention of inherited conditions, whilst the Claimant accepts there was mention of Fanconi anaemia. He agreed in cross examination that he was aware Professor Marsh would have to do a screening test for Fanconi. Further, when the Claimant was being asked questions supplemental to his witness statement he failed to recall the written consent form signed for Professor Dokal in February 2006 until he was taken to a copy of it.

I am satisfied that there was a policy in the department of sending, as a matter of routine, blood samples to Professor Dokal. I am satisfied that whilst there was no system for obtaining written consent – as clearly there should have been – there was a system of seeking verbal consent for blood to be sent to Professor Dokal. The process involved no additional invasive procedure since blood was drawn (by consent) for various tests in any event. I am satisfied that Professor Marsh did tell the Claimant that she wished to send some of his blood for research and that verbal consent was given.

But was the sample sent for research purposes? The Claimant’s case is that it was sent for diagnostic testing to see if the Claimant had DC, or perhaps another form of constitutional AA.

The starting point of the Claimant’s case arises from documents completed by Professor Marsh herself. In the Medical Records Core Bundle at SG 1.2 are notes made during or following the consultation on 25 March 2003. There is reference to “Fanconi anaemia screen” and “D congenita screen”.

At page SG 26.7 is the second page of a letter dated 7 April 2003 to Dr Amos, who had referred the Claimant to Professor Marsh in the first place. She wrote: “Fanconi anaemia screen negative and Dyskeratosis congenita screen awaited”.

Reliance is also placed upon documents originating from Professor Dokal. In various applications for grants he spoke of the availability of a screening test for DC. There certainly was a test that was available. But was it accessible?

Professor Dokal said that he simply could not offer a proper diagnostic screening service upon which reliance could be placed.

On the totality of the evidence, for reasons given below, I am satisfied, and so find, that there was no screening service offered by Professor Dokal or his team by virtue of which a clinician could insist on a blood sample being tested or screened for genetic mutations consistent with DC.

It seems clear to me that Professor Dokal, in the late 1990s and early 2000s would have liked to have been in a position to offer such a service, and the lure of such provision was at the forefront of his funding applications. But I am satisfied that he was simply not in a position to deliver such a service with the reliability in terms of speed of delivery and indeed certainty of service provision that would be required by users of such a service.

He explained this very clearly in his evidence, and I accept it. He explained that he is a clinical scientist and so whilst research is important, so is translating research into practical clinical applications. For that reason, his research was not performed upon anonymised blood samples, as explained further below.

He explained clearly that lack of resources, both in terms of staff and funding, limited the blood testing he was able to perform, in a manner wholly inconsistent with running a full testing service. He only ever had between 2 and 4 people working on the research and blood testing process. In 2003, the tests were limited to the DKC1 and TERC mutations, but there are now 8 recognised mutations. As he said, he would like to test all 45 genes, but simply cannot.

I am also satisfied that Professor Marsh was aware of the limitation on what Professor Dokal and his team could achieve. Why, then, did she use the terminology “screen” in her own notes and in correspondence to colleagues? There are two possible explanations that occur to me. The first is carelessness. This is the explanation given by Professor Marsh, when she describes the use of this terminology as a mistake. I am prepared to accept that explanation. However, I do wonder if the mistake is associated with a second, perhaps partial explanation related to a form of vanity – a wish to be seen to be associated with cutting edge developments which may one day result in the provision of a screening service such as that which exists for Fanconi anaemia. I express no concluded view on the matter, but it would explain the use of the word “screening” in the letter for Dr Amos, even though I am satisfied that Professor Marsh did not submit the sample with any screening purpose in mind.

That is not to say that Professor Dokal offered nothing of value. On the contrary, when a positive result was noted, steps were taken to notify the clinician who had procured and supplied the blood sample. This was done for two reasons. First there may well be treatment decisions that may be influenced or indeed determined by the knowledge of the results. Second, the family of the patient may wish to be involved in follow up research.

I did discern a willingness on the part of Professor Dokal to seek to expedite work on submitted samples if a specific request was made. It appears that he did so in respect of samples submitted by Dr Cavanagh. In this case, it seems to have been a telephone call on 1 September 2005 that led to a search for the sample of the Claimant’s blood and the commencement of work upon the sample. I am satisfied that this telephone call was prompted by Professor Marsh having learned that the Claimant had developed AVN. She at that stage considered for the first time that there may be a link between the development of AVN and a form of constitutional AA.

I have found that Professor Marsh had no reason to suspect DC earlier than she did, and thus had no cause to seek earlier expedition of any work that Professor Dokal could perform upon the sample of the Claimant’s blood. But I ought still to deal with what would have happened if the work had been expedited. What would Professor Marsh have done with the information that the Claimant did have DC, with reference to treatment advice she would have given. In particular, would she have recommended ALG treatment or would she have recommended treatment with Oxymetholone?

If Professor Marsh had asked Professor Dokal to expedite his work upon the sample of the Claimant’s blood, I am sure he would have done so. This follows from these considerations. First, Professor Marsh would only have made such a request if she had thought there was something unusual about the Claimant’s presentation, in other words if she suspected he may have DC even though in all other respects his presentation appeared to be “barn door” AA. Second, such a request from an esteemed colleague would have aroused Professor Dokal’s interest, in much the same way as did the request in what was described in evidence as the Zurich case.

The solicitors for the Claimant made enquiries directed to the research work of Professor Dokal and in particular his work on blood samples submitted to his laboratory, with a view to determining the length of time which elapsed between submission of a sample and the results being available. Professor Dokal dealt with this in a supplemental witness statement dated 8 February 2012. He explained that the time taken varies, depending on the resources available in the lab at any one time. He also explained that testing tended to be done in batches of about 20 samples at a time, so that reporting depended upon timing of the batches. At paragraph 5 of his statement he said this:

“However, the time taken to test any blood sample may also vary depending on the nature of the sample concerned. On 18 November 2010, [my colleague] Dr Vulliamy sent the Claimant’s Solicitors an anonymised example of a blood sample that was the closest we could find to the timescales they wanted. The Zurich case was sent to the lab on 10 November 2003 and reported on 15 January 2004 (positive for a TERC mutation). However, that sample was not comparable to the present case because it had significant research interest and was expedited. It was likely to be a case of autosomal dominant DC in the subject, possibly involving other family members the parents and two sisters, and the chances of finding a mutation in the TERC gene were thought to be relatively high. This was quite an exciting case for us and should not be held out as an example of standard reporting times or what ought to have happened in the Claimant’s case.”

If the Claimant’s sample had been expedited, how long would the work have taken? In the Zurich case, the time was just over 2 months. In the Claimant’s case, on the basis that the trigger was the telephone call on 1 September 2005 the period was again just over 2 months. The result was available by 11 November and sent to Professor Marsh by letter dated 17 November 2005. On the basis of this evidence, which seems to be the best available, a time scale of just over 2 months seems likely, and I so find.

If Professor Marsh had received the news that the Claimant had DC, what would she have done in terms of giving treatment advice? Her evidence, in simplified form, was that in 2003, there was no truly recognised treatment for DC arising out of a TERC mutation. It was not until 2006, she said, that there was a feeling that TERC mutation patients might be better off being treated by Oxymetholone, and so she would have recommended ALG. In 2003 she said that simply because one form of DC, caused by the DKC1 mutation, responded to Oxymetholone, it did not mean that DC caused by the TERC mutation would similarly respond, particularly since the TERC mutation seemed to arise in patients who had symptoms consistent with AA and did not have the classic triad of physical features associated with DC.

She did agree that, had she received the news in 2003 that the Claimant had a TERC mutation, she would have discussed the matter with colleagues, including Professor Dokal, but she said she would not have referred the Claimant to Professor Dokal. She was adamant that, had she known in 2003 that the Claimant had TERC mutation DC, she would have advised treatment with ALG.

Professor Dokal was asked what he would have done if, in 2003, he had tested the Claimant’s blood sample, discovered he had a TERC mutation and discussed the case with Professor Marsh. He said that it was important to decide if the patient had idiopathic or constitutional AA. In this case, the Claimant had constitutional AA and a unique TERC mutation. In those circumstances, Professor Dokal would have recommended Oxymetholone. However, had Professor Marsh said she wanted to treat with ALG, Professor Dokal said he would have had in mind the fact that there had then never been a clinical trial to test the respective effectiveness of ALG and Oxymetholone. He said it was not and never had been his approach to dictate how another clinician’s patient should be managed.

Given the eminence of Professor Dokal and his unrivalled experience in the field of constitutional AA, I would find it surprising if Professor Marsh declined to follow treatment advice given by Professor Dokal. I appreciate that Professor Marsh, in her evidence, sought to justify the hypothetical treatment decision – what would she have done had she known the Claimant had a TERC mutation in 2003? I think that on this occasion, Professor Marsh has convinced herself that the knowledge of the TERC mutation would not have affected her treatment advice, and to that extent I accept that she has given this evidence in good faith. But I do not think that she is being accurate with herself. I have little doubt that if Professor Dokal had suggested Oxymetholone as the appropriate treatment, Professor Marsh would have adopted that suggestion and advised the Claimant accordingly. And I have no doubt but that the Claimant would have accepted that advice.

However, I am satisfied that Professor Marsh would only have contacted Professor Dokal if she had cause to suspect that the Claimant had constitutional AA – DC – rather than idiopathic AA. If she had that suspicion, I consider it likely, and I so find, that she would have delayed treatment by way of ALG or Oxymetholone. As a result of findings already made, it follows that had she contacted Professor Dokal to expedite the result and waited before initiating treatment, she would, following notification of the results and discussion with Professor Dokal, have recommended treatment with Oxymetholone. Thus the Claimant would not have been treated with ALG and would not have received any dose of Prednisolone.

In the light of my findings so far, Professor Marsh was justified in treating the Claimant on the basis that he had idiopathic AA. The treatment options were ALG together with Prednisolone, or Oxymetholone. It was not negligent for Professor Marsh to recommend ALG and Prednisolone, which is the standard treatment for AA. Moreover, it was not negligent to commence treatment more or less immediately. The evidence is that the Claimant was diagnosed as having Non Severe AA, but nevertheless he had begun to receive blood transfusions, the platelet count was towards borderline severe, and the haemoglobin level was falling. The Claimant’s sister was not a bone marrow match. Whilst Professor Marsh accepted that commencement of treatment could be left a few weeks, there were risks associated with multiple blood transfusions, including a reduction in the chances of bone marrow transplant succeeding in the future.

There was exploration in evidence of the fact that treatment was commenced before a further trephine bone marrow biopsy had been performed. Professor Marsh explained that there had been 2 previous trephine biopsies. In this instance, the aspirate biopsy was consistent with AA, as had been the previous 2 trephine biopsies. As a matter of clinical judgment she felt it appropriate to commence treatment, but, as she put it “to be on the safe side” she ordered another trephine and aspirate sample. That seems to me to be adequate.

It is agreed that AVN is an acknowledged side effect of the administration of Prednisolone, albeit a rare side effect. It is common ground that the Claimant was not warned about this side effect before he agreed to this form of treatment.

The Claimant’s case on this issue is not simply that he should have been told of this specific risk. He puts his case on the wider basis of a breach of the obligation to provide him with all relevant information relating to his condition and treatment. Reliance is placed upon the cases of Birch v University College London Hospital NHS Foundation Trust [2008] EWHC 2237 (QB) and Chester v Afshar [2004] UKHL 41, [2005] 1 AC 134.

In Birch the Claimant was properly warned that undergoing the procedure of cerebral angiogram carried with it a 1% risk of a suffering a stroke. This risk materialised. What the Claimant was not told was that an MRI scan was an alternative diagnostic procedure which, although not as good a diagnostic procedure as the cerebral angiogram, carried with it no risk of stroke at all. It was held that this amounted to a breach of duty. The judge accepted that, had the Claimant been properly informed, she would not have consented to the angiogram. Thus she succeeded.

In Chester the Claimant was advised to undergo a spinal procedure which, even if performed without negligence, carried with it a risk that the Claimant would develop cauda equina syndrome. Negligently, she was not warned of this risk. She gave consent to the procedure and developed cauda equina syndrome. The judge found that if she had been warned of the risk, she would have taken advice but still would have undergone the procedure, albeit on a different occasion.

The House of Lords, by a majority, held that the duty to warn of such matters was closely connected to the issue of consent which was central to the Claimant’s right to exercise an informed choice. Thus the injury was to be treated as having been caused by the breach of duty to vindicate the Claimant’s right of choice and to provide a remedy for the breach.

Thus the Claimant makes two linked complaints. First he says simply that he should have been told that AVN was a potential side effect. Second he says he should have been given information about other possible treatment options, including Oxymetholone.

The Defendant’s case is that although the development of AVN was a known side effect, the risk of its occurrence was so small that there was no duty to warn of it. The Defendant argued that this was particularly so in the case of administration of Prednisolone in St George’s Hospital because of the very low doses that were in fact administered in conjunction with the administration of ATG.

Professor Marsh said that in 2003 she did not warn patients of the risk of developing AVN as a side effect of the administration of Prednisolone. She explained that this was because it was a rare side effect and that she had noted that administration of a standard dose of Prednisolone gave rise to an increased incidence of the development of AVN. In consequence, the practice at St George’s Hospital was to administer a reduced dose. No cases of AVN were found in any patient who had received this new low dose other than the Claimant.

Dr Cavanagh gave evidence supporting that view. In cross-examination it was put to him that the Claimant should have been told that administration of steroids carried with it a small risk of the development of AVN. Dr Cavanagh’s evidence was that use of a low dose was deliberate so as to ensure as modest a toxicity profile as possible. He pointed to the fact that he was aware of only one case where AVN had resulted from the administration of such a low dose of Prednisolone, that being the case of the Claimant himself. He concluded by saying that “they”, meaning the clinicians at St George’s “did not counsel about it then and neither would I”.

He was pressed on this. It was put to him that it was logical that if it was current practice to tell a patient all of the side effects of ATG, it would be equally logical to discuss AVN as a side effect of the administration of Prednisolone. Dr Cavanagh said that he was not sure that he could agree with that. He said that one “cannot discuss all of the side effects, no matter how unlikely they are”.

No evidence was called on behalf of the Claimant to counter this view. Thus on the issue of failure to warn on its own, the Claimant can only succeed if he can show that the view of Dr Cavanagh, as representing a responsible and reasonable body of medical opinion, is logically indefensible on the basis suggested in Bolitho v City & Hackney Health Authority [1998] AC 232.

In support of his submission that such view is logically indefensible, Mr Booth relied upon a letter written by Professor Marsh dated 2 August 2005 in connection with this case. It is found at E3 at tab 34, page SG28.1 at 28.3. She wrote this:

“Avascular necrosis is not a common side-effect of Prednisolone when it is used in the context of treatment with ALG for aplastic anaemia. St George’s Hospital is a national tertiary referral centre for aplastic anaemia and out of 147 patients who have had one course of ATG we have only seen one case of avascular necrosis using low dose Prednisolone. Because avascular necrosis affects <1% of people when used in this way, I do not routinely mention this as a side effect when I discuss ALG treatment with patients. It is widely appreciated, of course, that avascular necrosis is a serious side-effect and associated with considerable morbidity.”

It must be appreciated that the Claimant is the single patient in the 147 patients referred to. It is true that practice about giving warnings may have since changed. However, it does not seem to me that the decision at the material time not to warn about the development of an extremely rare side effect which had hitherto never manifested itself in patients given the low dose administered at St George’s Hospital can be said to be logically indefensible.

Can the Claimant succeed by another route? Mr Booth argued that he can. He relied upon the cases of Chester and Birch mentioned above.

To the extent that it may be argued that had administration of Prednisolone been postponed to another occasion, AVN would probably not have developed, there is simply no evidence in support of such a proposition. On the contrary the only evidence on this issue also came from Dr Cavanagh. His evidence on this issue came within the context of cross-examination about the administration of Prednisolone generally, which is dealt with above. However, towards the end of his evidence in cross-examination he was asked if the susceptibility of a person to the effects of Prednisolone might vary over time. Dr Cavanagh said that this was not so. He said that if a person is susceptible to develop AVN as a result of the administration of Prednisolone, this will not wax and wane over time. There was, he said, no plausible biological reason for that. He explained that he gave this opinion, which he described as a hypothesis, as a clinician who has administered steroids to a wide range of patients. His opinion was that the Claimant developed AVN because he had a significant predisposition to develop that condition. When challenged that there was “no science on that” he replied “except that AVN is a recognised side effect in patients who have DC”. Mr Booth put his case clearly when he suggested to Dr Cavanagh that statistically, if ATG and Prednisolone had been administered at a different time, the Claimant would have been unlikely to have developed AVN. Dr Cavanagh disagreed, saying that the individualised risk of the Claimant developing AVN consequent upon the administration of Prednisolone was “close to 100%”.

Thus I have no hesitation in concluding that it was not negligent to fail to discuss with the Claimant the remote risk of the claimant developing AVN as a result of the administration of Prednisolone.

That being so there is no scope for identifying a remedy for a breach of duty, as in Chester, because there is no breach of duty.

Moreover, even if the risk had been disclosed, the Claimant would have accepted the advice to undergo ALG treatment with Prednisolone, not least because he would have been told that there had hitherto been no case of anyone treated with the low dose regimen at St George’s ever going on to develop AVN.

Finally, even if alternative treatment options had been discussed, it is clear that Professor Marsh would have recommended ALG with Prednisolone and the Claimant would have accepted that advice. Oxymetholone is a treatment which itself carries significant risks of side effects, as Dr Cavanagh mentioned in evidence when describing a patient who had lost half their liver as a result of administration of Oxymetholone. ALG is the first line treatment for AA.

There was nothing in the clinical presentation or history of the Claimant in March 2003 to cause Professor Marsh to suspect that the Claimant had DC. She was justified in not so suspecting. There was no negligence.

The Claimant gave verbal consent for a sample of his blood to be sent to Professor Dokal for research purposes.

The sample was indeed sent for research purposes. Professor Dokal did not in 2003 nor does he now offer a diagnostic service as such, although he will try to expedite sample testing if asked to do so in appropriate cases.

There was no reason for Professor Marsh to seek expedition in 2003, and it was not negligent of her to fail to do so.

It was reasonable for Professor Marsh to recommend treatment by ALG and Prednisolone. There was no obligation to discuss alternative treatments and no obligation to warn of the risk of AVN.

If Professor Marsh had been told by Professor Dokal that the Claimant had DC before any treatment had been administered, she would have sought his advice and would probably have accepted his recommendation to treat with Oxymetholone. However, this did not happen and I make this finding simply for the sake of completeness.

In the event the claim fails and there will be judgment for the Defendant.