Otley v Barking and Dagenham
R (on the application of Otley) v Barking and Dagenham NHS Primary Care Trust

National health service – Drug – Supply of medicine or drug – Drug for treatment of metastatic colorectal cancer – Clinical and cost effectiveness – Difficult decisions panel of primary care trust refusing to make drug available to claimant – Whether panel's decision irrational and unlawful

[2007] EWHC 1927 (Admin), CO/4396/2007, (Transcript: Wordwave International Ltd (A Merrill Communications Company))

18 JULY 2007
J Howell QC and S Knaffer for the Claimant
J Hyams for the Defendant
Sternberg Reed, Barking; Capsticks
[1] The Claimant is 57. She has metastatic colorectal cancer. Her condition was diagnosed after a significant delay on 17 November 2005. On 1 December 2005, she had a sigmoid colectomy at King George's Hospital. Metastases, secondary tumours, were found in her liver. They were too large to be resected then. She was referred to Dr Raouf, a consultant oncologist. He prescribed chemotherapy for her, Oxaliplatin plus 5FU. There was a very good symptomatic response. The size of the liver tumours appeared to shrink when imaged on a CT scan. She was referred to the Royal London Hospital for liver resection on 20 June 2006. The tumours were found to be larger than had been suggested by the CT scan. The resection was therefore not possible.

[2] The liver surgeons referred her back to Dr Raouf. On 19 July 2006, he prescribed a different course of chemotherapy, Irinotecan and 5FU. She had five cycles. They were unsuccessful. By 18 September 2006, she had a palpably enlarged liver and there was a rise in the tumour markers (that is to say protein in a blood sample). Further, she tolerated the treatment extremely poorly. Dr Raouf concluded that continuance of that treatment would be “of absolutely no value”. Ms Otley's sister discovered the existence of a biological drug, Avastin, on the internet. The effect of Avastin is to inhibit the growth of blood vessels in tumours so as to permit chemotherapy to retard their growth or, in a small percentage of cases, perhaps as many as 14% of all cases of metastatic colorectal cancer, to shrink them sufficiently to permit resection.

[3] Avastin is licensed to be used in the United States of America and in many continental countries but not in England and Wales. It is not one of the drugs available for normal prescription within the National Health Service. Its cost has been variously estimated at between a £1,000 and £1,500 per cycle. The precise figure does not matter a great deal. I take to be about £1,200 per cycle. Ms Otley and her sister had available to them £15,000 to fund the private prescription and administration of Avastin. Dr Raouf prescribed privately a combination of Oxaliplatin, 5FU and Avastin.

[4] The funds available to Ms Otley permitted five cycles to be administered. The response was excellent. There were minimal side effects. She felt much better in herself and the tumour markers had reverted to normal after only two cycles. Ms Otley believes that MRI scans performed on October 2006 at the Royal London Hospital and November 2006 at King George's Hospital revealed a reduction from ten millimetres to eight millimetres in the size of the tumours and that Dr Raouf told her so. Dr Raouf in recent correspondence has denied that he did so and further states that the November 2006 MRI scan showed no reduction and that a further MRI scan performed in January 2007 showed no change in the size of the tumours. However, he states that conclusion in the light of the RECIST criteria, which require a reduction of 30% in the size of a tumour before a decrease in size is acknowledged. Her recollection and his assessment of the MRI scans are accordingly not inconsistent, even though her recollection and his of what he said to her plainly is. I have no means of determining which of them is right.

[5] Dr Raouf applied to the Barking and Dagenham Primary Care Trust to fund the further prescription of Avastin in conjunction with Oxaliplatin and 5FU. He did so first by a letter of 22 January 2007 in which he stated, after reciting the sigmoid colectomy:
“She was started on first line chemotherapy using Oxaliplatin and 5 FU as per protocol and she achieved a very good symptomatic response and improvement in her CT scans in the liver metastases. She was referred to the Royal London Hospital for consideration of resection of her liver metastases, but unfortunately at operation it was found that the CT scan had under staged her disease and operation could not be done. She was sent back to me for further chemotherapy and we started her on second line chemotherapy using irinotecan and 5 FU. Unfortunately there has been no response to irinotecan and, in fact, her liver metastases have grown bigger and she has started having a lot of symptoms from them. At this juncture she sought the help of her sister who agreed to fund her for Avastin therapy, which is a VGEF receptor inhibitor, which added to chemotherapy improves the response rate and indeed survival. Miss Otley had four cycles of oxaliplatin, 5 FU and Avastin with excellent response, but funding could not be found for further therapy and she had to continue on chemotherapy without Avastin.

Ms Otley is extremely young and very fit despite her condition . . . .

There is mounting evidence that adding Avastin to chemotherapy in metastatic colorectal cancer does improve the response rate and indeed survival. This has been confirmed in first and second line therapy and indeed the resistance usually encountered on chemotherapy alone is reversed with the addition of Avastin. I am aware that NICE has preliminarily reviewed the use of Avastin and voted against it on cost effectiveness rather than clinical reasons.”

He enclosed summaries of studies undertaken to the PCT.

[6] Decisions about the prescription of non standard drugs are taken in this Trust by a Difficult Decisions Panel. It comprises normally non executive directors and a medical director or assistant director and others. On 22 February 2007, the Panel decided that further evidence needed to be clarified before a decision could be made. Dr Raouf responded by a letter of 13 March 2007. He summarised that which he had already said in his earlier letter and concluded with these words “While adding bevacizumab [the generic name for Avastin] is not going to cure her, it may certainly improve her survival from this terrible illness . . . .” He enclosed further summaries of studies undertaken into Avastin, in particular a reference to the eastern trial known as the E3200 trial performed in 2005 which suggested an increase in overall survival by two months compared with Oxaliplatin and 5FU alone. He also enclosed an abstract of a smaller study of 16 patients which suggested that the use of Avastin in combination with chemotherapy produced an overall response rate of 37.5% and a stable outcome of 25%. The overall response rate refers to a partial reduction in the size of tumours when the treatment is administered and the stable outcome to no reduction but no increase either.

[7] The Panel, which met on 22 March 2007, decided that no further evidence had been produced to persuade them that sanctioning the use of Avastin would significantly prolong Ms Otley's life or be a cost effective use of NHS resources. At that stage, solicitors became involved on the part of Ms Otley and they invited the Panel to reconsider. The Panel agreed to do so and held a special and urgent meeting on 3 May 2007. By a letter dated 20 April 2007, addressed to Ms Otley's solicitors, the Panel requested information on Ms Otley's clinical state prior to and following treatment with Avastin. That prompted a response from Dr Raouf by a letter of 25 April 2007, to which I will refer in a moment. The Panel also caused there to be prepared a critical analysis of the information publicly available about the effectiveness and cost effectiveness of Avastin when used in conjunction with other drugs.

[8] It had a settled policy on difficult decisions, drafted on 14 August 2006 and due to be reviewed on 25 May 2007. No criticism of the lawfulness or rationality of that policy is made. For present purposes, it contains the following provisions:

“The PCT is required to consider applications to fund a number of procedures which are excluded from its service level agreements. These may be for mainstream, but expensive treatments. They may be for novel procedures, where there is limited evidence of effectiveness.
Decisions about whether to fund such cases must be taken carefully, both to ensure that no harm comes to the patient, but also to ensure that best use is made of health service resources. Decisions must be made in the context of the Human Rights Act and other statutes and guidance appertaining to the National Health Service.”

A decision making framework is set out. It provides:

“The framework requires that consideration is given to:

i. evidence of effectiveness
ii. equity
iii. patient choice
iv. cost effectiveness
v. due regard to exceptional circumstances.”

Under the heading “Effectiveness” it states:

“Funding should not be approved where there is good evidence that the treatment is not effective. Equally, sound evidence about effectiveness ought to lead to approval of funding, although the PCT will need to consider the impact of funding on the health of the whole population.”

Under the heading “Equity”, the unexceptional statement is made that “Equity requires maximising the welfare of patients within available resources and giving priority to those in most need.” Under “Patient choice” it is noted that “Outcome measures used in research need to include those which matter to the individual patient,” but that the Trust will not fund an intervention merely because a patient wants it. There then follow unexceptionable references to the relevant provisions, arts 2 and 3 of the European Convention on Human Rights.

[9] The policy itself contains no detail about exceptional circumstances. That detail was, however, provided to the Panel by the critical appraisal of Avastin for use in metastatic colorectal cancer, dated 27 April 2007, to which I have already refered, which was prepared by Jim McManus, the head of the Health Improvement Directorate for the Trust. It recommended “Exceptionality Criteria” in these terms:

“7.1 This appraisal recommends that because of the issues of cost effectiveness and state of the evidence, bevacizumab is not routinely commissioned but is only commissioned in exceptional circumstances.
7.2 This raises the issues of what counts as exceptional. Current legal opinion is that exceptional is not just 'not the norm'. There needs to be a baseline or comparator for something to be exceptional against. The comparator or baseline should be the cohort of people with the condition. So exceptionality here is exceptional for someone with metastatic colorectal cancer compared to the rest of the cohort of patients with such cancer being treated.
7.3 Suggested exceptionality criteria for considering applications for this drug are below. This is an initial and not an exhaustive list. Item 1 is taken from the trial populations:

1. Fitness of the patient in terms of ability to benefit from chemotherapy. This has at least some salience in the
2. Differences in clinical circumstances to the rest of the cohort of patients such as:
a. Reactions to other treatment, tolerances etc
b. Specific clinical history and prognosis
c. Other clinical circumstances exceptional compared to the rest of the population with this cancer.”
The criteria went on to deal with a matter that the panel found rightly to be of no relevance in these circumstances: other social circumstances.

[10] That recommendation followed upon a summary of studies hitherto undertaken into the effectiveness of Avastin. Two are of particular interest. First, the updated E3200 study of 20 April 2007. In Mr McManus' summary he quoted the outcome of that study as follows:
“The median progression free survival for the group treated with FOLFOX4 [Oxaliplatin plus 5FU] in combination with bevacizumab was 7.3 months, compared with 4.7 months for the group treated with FOLFOX4 alone . . . .”

He also noted the conclusions of the study about the response rate in these words “The corresponding overall response rates were 22.7%, 8.6% and 3.3% respectively . . . .”

[11] That is a summary of a paragraph in the E3200 report which does not to the lay reader set out its full significance. What Mr McManus was referring to, as would have been readily understood by the Panel, was that there was an increased and enhanced response rate of 22.7% in those patients treated with Oxaliplatin and 5FU plus Avastin by comparison with those who were treated with Oxaliplatin plus 5FU alone or with Avastin alone. But what may not have been apparent to the Panel, and certainly would not be apparent to me as a lay man, was that, by response rate, the authors of the report meant circumstances in which the size of tumours had been reduced by at least 30%. The RECIST criteria refer to a reduction of at least that size when identifying a response rate to treatment. That indeed is the criterion to which Dr Raouf referred, as I have already mentioned. The significance of that possibility in Ms Otley's case is that her only chance of long term survival, it is common ground, is if her liver tumours can be reduced to no more than five millimetres, a reduction which would permit resection, for without surgery her life expectancy is to be counted in a few months.
[12] Mr McManus went on to summarise the NICE recommendations of 2007, which were to the effect that it was not cost effective to prescribe Avastin for first line treatment, that is to say the first of successive groups of cycles of treatment based on chemotherapy. What Mr McManus did not refer to in his critical analysis was that part of the NICE guidance in para 2.5 of its 2007 report, which was to the effect that in approximately 14% of cases of chemotherapy “chemotherapy may render unresectable liver metastases operable”. The effect of those omissions in Mr McManus' critical analysis may (I emphasis may for reasons which I will explain in a moment) have been that it was not made abundantly clear to members of the Panel, in particular to the lay members, that the prescription of Avastin in combination with chemotherapy was capable of reducing secondary tumours in the liver to such a extent as to make them operable and so to give a patient a slim chance of long term survival.

[13] The meeting of the Panel lasted two hours. It is apparent from the notes, both the typed notes of the meeting and the handwritten notes of two of its members, that anxious consideration was given to Ms Otley's plight and to Dr Raouf's request on her behalf that funding be provided for Avastin to be added to the treatment that she was receiving. The Panel dealt with a number of matters that are not now relied upon, in my view plainly correctly, and then focused on clinical matters and cost effectiveness. The typed notes suggest that what the Panel had in mind was the short term effect on Ms Otley's life of the prescription of Avastin. Nothing in the notes suggests that they expressly had in mind the slim chance of longer term survival if Avastin were prescribed.

[14] The Panel applied its August 2006 policy by going through each of the items contained in it. Under “Evidence of Effectiveness” and “Clinical/Cost”, the following observations by Dr Sharma, the acting medical director who provided the medical imput into the discussion:
“Dr AS questioned the evidence for clinical effectiveness of Avastin over and above the other two drugs in the three drug cocktail.
In the case mix reviewed by NICE it was DR AS's understanding that the patient's profile was consistent with the cohort that NICE have looked at and their evidence and recommendations were directly relevant on a population basis to the patient in question.
Avastin was introduced to Ms O due to her low tolerance of other interventions. AS noted that no information was given on whether her other medication was reduced when Avastin was added to her regime and therefore it was not possible to establish which had had the greater effect.

Ms O has not received Avastin for several months and her disease does not appear to have significantly progressed in that time. She has been receiving other treatments that are licensed and available on the NHS.”

[15] Two observations can be made about that passage. First, Professor Sikora, an eminent consultant oncologist, has prepared two reports that are highly critical of that reasoning. He says that the precise ratio of Avastin to other drugs in the treatment is not a relevant factor. Given the current state of knowledge about these treatments, which are at or near the cutting edge of medicine, there is simply no evidence about the precise ratio of Avastin to other drugs required to produce a beneficial response. It is the simple fact that the cocktail of Oxaliplatin plus 5FU and Avastin produced beneficial results which matters. There is in my view force in Professor Sikora's criticism. I cannot conceive of any answer which could have been given which would have provided useful information to Dr Sharma or the Panel in response to his request.

[16] The second observation that he made is that the Panel in this aspect of its discussion was plainly focused on short term survival and on palliative care during the remainder of a much shortened life for Ms Otley. That observation is confirmed by other passages in the notes of the meeting. Under the heading “Patient Choice”, the notes record:

“Dr Raouf has indicated that treatment for this patient with Avastin would be ongoing until such time as her disease progresses further. He has also indicated that a CT scan will be necessary after four five treatments to assess any response to the treatment before continuing with further treatments.”

Under the heading “Human Rights”, the following was noted “AS felt that the statistical expectation of two – six months was not a certainty and Ms O's response to the drug had not been sufficiently proven.”

[17] In a witness statement prepared for the purpose of these proceedings, Dr Sharma puts the discussions in a markedly different context. He notes in para 11(iii) that “Dr Raouf reported that, whilst taking this combination, Ms Otley had symptomatic relief and her metastases shrunk from 10mm to 8mm.” And in para 24(iii):

“Members, myself included, could not identify sufficient evidence that Avastin was the active ingredient in Ms Otley's reported improvement or that further treatment would shrink her liver metastases to render them operable.”

[18] While no criticism is, or could properly be, made of Dr Sharma's good faith in the matter, his recollection about what occurred at the meeting is not supported by the minutes or by any other contemporaneous document. The tone of the minutes suggest that long term survival was not at the forefront of the Panel's discussions and perhaps may not have been a feature of them at all. For the purpose of determining whether or not the Panel's decision can be upheld, I prefer the contemporaneous documents to Dr Sharma's current recollection.

[19] An obviously important feature of the Panel's discussions were the exceptional circumstances claim. Social circumstances were considered but do not feature in any criticism of the decision. As far as exceptional clinical circumstances are concerned, the minutes state:
“She does fit the cohort of patients the drug has been tested on – age, no other medical conditions, relatively fit. AT [Angela Todd, the non executive director] felt that this did not make her an exceptional case in relation to the study criteria. AS felt that Ms O did fit the criteria used in the studies but there was not sufficient evidence of her personal and medical profile to make her an exceptional case.”

[20] Professor Sikora, in robust criticism of that conclusion, states that Ms Otley plainly does fit the exceptionality criteria contained in the risk analysis document. Save in one important respect, his conclusion seems to me to be obviously right. Ms Otley was at the time when the decision was made, as she had been throughout, relatively fit. She was young by comparison with the cohort of patients suffering from this condition. Her reactions to other treatment, in particular to Irinotecan plus 5FU had been adverse. Her specific clinical history suggested that her reaction to a combination of chemotherapy and Avastin had been of benefit to her. By comparison with other patients, she, unlike many of those the subject of the studies, had suffered no significant side effects from a cocktail which included Avastin. All of those points are fairly made by Professor Sikora.

[21] The one significant respect in which his criticism may not be justified is that it may be the case that Ms Otley's prospects of long term survival may not be enhanced, even to the slim extent indicated by the studies, by a cocktail which includes Avastin. Professor Sikora, like Ms Otley, until only a few days ago, was of the opinion that the MRI scans, taken in October and November 2006, had revealed a reduction in the size of the tumours of two millimetres. If that is not so, then his underlining premise that this treatment does improve her chances of long term survival by a small but significant amount may not be right. For reasons which I have explained, the facts on that question are far from clear. But with that qualification, I agree with Professor Sikora's criticisms of the conclusions of the Panel.

[22] The final conclusion of the Panel to which I must refer is oddly contained under the heading “Human Rights”. It states: “The Panel felt that as there were other treatments available to Ms O not funding this treatment did not breach art 2 or 3 of the Act.” That statement appears to be based either upon a misreading of the information provided by Dr Raouf or upon a conclusion for which there is no evidence. As Dr Raouf had said in his letters, the only treatment which it was open to him to provide in the immediate future, Irinotecan plus 5FU, had not worked in the past. Further it had had seriously adverse affects for Ms Otley. That treatment accordingly does not fit within the description “other treatments available to Ms O” save in the most literal sense. It was certainly not treatment which on the past history had any realistic prospect of providing a significant benefit, short or long term, for her. It is not possible for me to discern from the documents available to the Panel what if any other treatments it may have had in mind.

[23] By this claim, Ms Otley seeks an order in the first place to quash the decision of the Panel to refuse to fund the treatment, including Avastin. I remind myself of the elementary propositions of law identified by Sir Thomas Bingham MR in R v Cambridge Health Authority ex parte B [1995] 2 All ER 129, [1995] 1 WLR 898, [1995] 2 FCR 485, in which he observed at 905B:

“. . . the courts are not, contrary to what is sometimes believed, arbiters as to the merits of cases of this kind. Were we to express opinions as to the likelihood of the effectiveness of medical treatment, or as to the merits of medical judgment, then we should be straying far from the sphere which under our constitution is accorded to us. We have one function only, which is to rule upon the lawfulness of decisions. That is a function to which we should strictly confine ourselves.”

and at p 906D to F:

“I have no doubt in a perfect world any treatment which a patient, or a patient's family, sought would be provided if doctors were willing to give it, no matter how much it cost, particularly when a life was potentially at stake. It would however, in my view, be shutting one's eyes to the real world if the court were to proceed on the basis that we do live in such a world. It is common knowledge that health authorities of all kinds are constantly pressed to make ends meet. They cannot pay their nurses as much as they would like; they cannot provide all the treatments they would like; they cannot purchase all the extremely expensive medical equipment they would like; they cannot carry out all the research they would like; they cannot build all the hospitals and specialist units they would like. Difficult and agonising judgments have to be made as to how a limited budget is best allocated to the maximum advantage of the maximum number of patients. That is not a judgment which the court can make.”

[24] That principle was restated by Auld LJ in slightly different words in R v North West Lancashire Health Authority [2000] 1 WLR 977 at 991E to F, [2000] 2 FCR 525:

“As illustrated in the Cambridge Health Authority and Coughlan cases, it is an unhappy but unavoidable feature of state funded health care that Regional Health Authorities have to establish certain priorities in funding different treatments from their finite resources. It is natural that each Authority, in establishing its own priorities, will give greater priority to life threatening and other grave illnesses than to others obviously less demanding of medical intervention. The precise allocation and weighting of priorities is clearly a matter of judgment for each Authority, keeping well in mind its statutory obligations to meet the reasonable requirements of all those within its area for which it is responsible. It makes sense to have a policy for the purpose – indeed, it might well be irrational not to have one – and it makes sense too that, in settling on such a policy, an Authority would normally place treatment of trans-sexualism lower in its scale of priorities than, say, cancer or heart disease or kidney failure.”

[25] Those citations demonstrate, if it needed to be demonstrated, the severe limits on the ability of this court to review decisions of the kind taken by this panel. I am unimpressed by arguments which go to procedure. Mr Howell has submitted that the critical analysis should have been disclosed to Ms Otley's advisers before it was relied upon by the Panel. At some stage, although not relied upon by him, it was even suggested in correspondence that the Panel should allow her lawyers to attend its meeting. These procedures, which may be appropriate for trials and inquiries into such matters as whether or not to grant planning permission play no part in my view in decisions of the kind which this panel had to take. It is, of course, obvious that if, in considering matters such as the critical analysis, it reaches a conclusion that is shown to be demonstratably wrong or legally flawed, then its decision can be corrected by this court, but that is so whether or not such a document would first have been shown to his legal advisers.

[26] I approach my task on a very conventional basis. The question which I have to ask is whether or not the reasoning and decision of the Panel was rational and so lawful on Wednesbury grounds (see Associated Provincial Picture Houses Ltd v Wednesbury Corporation [1948] 1 KB 223, [1947] 2 All ER 680). I have identified already respects in which in my view the decision of this panel was not rational. I summarise them in headline form. First, Dr Sharma's query about the ratio in which Avastin had been prescribed by comparison with other components of the cocktail was an irrelevant query. Secondly, there were no other treatments in practice available to Ms Otley amongst those that could be prescribed within normal National Health Service standards which were likely to have any benefit for her. Thirdly, the Panel did not take into account the slim but important chance that treatment including Avastin could prolong Ms Otley's life by more than a few months. Fourthly, on any fair minded view of the exceptionality criteria identified in the critical analysis document, her case was exceptional.

[27] For those reasons, this Panel's reasoning was in my view flawed. This is not a case as in R (Rogers) v Swindon National Health Service Primary Care Trust [2006] EWCA Civ 392, 89 BMLR 211, [2006] 1 WLR 2649, in which the policy of the Trust and its Difficult Decisions Panel is open to criticism. On the contrary, the policy is entirely rational and sensible. Nor is it a case, on close analysis, in which the availability of scarce resources is a decisive feature. The policy properly provides that the allocation of resources is an element in every decision of this kind. But the course proposed by Dr Raouf, for which he sought funding, was at least in its initial stages a course which required the allocation of only relatively small resources. His proposal was for four or five cycles of treatment, including Avastin, at the end of which imaging would be done and progress reviewed. The bleak conclusion for Ms Otley is that, if at the end of those four or five cycles no improvement is revealed, then her slim chance of long term survival will be lost. But the course proposed by Dr Raouf did not on any reasonable view require this Trust to put at risk the interests of other patients or, in the words of its own policy on difficult decisions, require it “to consider the impact of funding on the health of the whole population”. Accordingly, the decision of the Panel falls be analysed on the basis that although the allocation of resources is a factor, it is not capable of being a decisive factor in the decision which it had to make.

[28] For the reasons which I have given, I quash the decision of the Panel and invite representations about what should happen in the future.

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