WIT: A window on tensions in clinical trials

(Warning: contains plot spoilers!) Adapted from Margaret Edson’s 1999 Pulitzer Prize winning play, Wit tells the tragic story of Professor Vivian Bearing (Emma Thompson). Vivian, a ruthless scholar of 17^th Century English poetry, is diagnosed with advanced stage 4 metastatic ovarian cancer. Dr Harvey Kelekian (Christopher Lloyd), Vivian’s consultant physician and leading figure in this area of medical research, explains that the most effective treatment option she has is an aggressive experimental chemotherapy at the full dose.

Professor Vivian Bearing (Emma Thompson)

She cautiously consents to the therapy and embarks on a degrading regime of eight cycles, which no other patient has completed before. With a fearless determination, Vivian does everything the doctors ask of her, and as such illustrates the central ethical issue observed in this film; the conflict of interest witnessed between clinical therapy and clinical research. Throughout, this is entangled with clinical incompetence, issues of informed consent, end of life decisions and Vivian’s frustration with the hospitals insensitive mechanistic approach to their patients, having been asked repeatedly “How are you feeling today?” (00:04:10 – 00:05:25)

As a clinical researcher, a physician may wear a number of hats. On the one hand, they are in pursuit of patient-centred beneficence, seeking to maximise patient care and welfare. On the other, they wish to push back the boundaries of scientific knowledge.  This can present a conflict of loyalties relating to a raft of issues. The first and most prominent is that of ‘professional integrity’. The relationship between the investigator and the patient must be ethically sound and decisions must be made with the greatest moral scrutiny to ensure patient nonmaleficence. This is, of course, easier said than done as is evident throughout this film.                                     

Dr Harvey Kelekian (Christopher Lloyd)

The opening scene of the film (Start – 00:04:10) sees Dr Kelekian diagnosing Vivian and discussing the possible treatments she should have. He suggests an experimental combination of chemotherapy, which is targeted specifically at patients like her, “This treatment is the strongest thing we have to offer you, and as research it will make a significant contribution to our knowledge”.  This highlights three main issues surrounding Vivian’s motivation to consent to this experimental treatment;

• She is a highly vulnerable patient. She has just been diagnosed with advanced stage 4 metastatic ovarian cancer and, as she herself notes, “there is no stage 5”. What hope does she have, if any? Vivian may cling to any treatment which might offer a therapeutic benefit.
• The words of Dr Kelekian imply that there is no other treatment option “this is the strongest thing we have to offer you”. 
• “It will make a significant contribution to our knowledge”, suggests that her participation would altruistically help future patients and future medical development.

Vivian consents to the treatment Dr Kelekian has suggested; the experimental regime may possibly have a therapeutic benefit, she has little or no other options and the knowledge gained may help others. Do such circumstances promote fully autonomous informed consent without coercion or are the boundaries sufficiently blurred to tempt patients into apparently helping themselves whilst endeavour to help others?

The therapeutic intent proposed by the experimental treatment in this scenario, is often called ‘therapeutic misconception’, a term coined by Paul Appelbaum, Loren Roth and Charles Lidz in 1982. It describes the tendency of patients involved in high risk therapy trials to believe that such treatment was designed for their personal health care, whereas such trials may, in fact, offer them little or no direct benefit. This is particularly important with regards to the clinician, whom may seek a justifiable cause to enrol a patient onto such a clinical trial. The clinician may subconsciously engage in some form of ‘cognitive dissonance’ which blurs their judgement to believe in a possible therapeutic consequence from a purely research aim.    
There are countless instances throughout the film where clinical therapy seems only a hindrance to the research objectives. Dr Jason Poser (Jonathan M Woodward), a research fellow working under Dr Kelekian and a previous student of Vivian’s, is just as determined in research and neglectful of his clinician duties as his senior.

Susie (Audra McDonald)

In one particular scene, Vivian is admitted into hospital with a severe fever and looking particularly unwell (00:36:54 – 00:40:45). Her nurse Susie (Audra McDonald) who shows compassion throughout the film, suggests to Jason;
Susie – “I think you need to speak to Kelekian about lowering the dose for the next cycle, it’s too much for her like this”
Jason – “Lower the dose no way. She can handle it. She’s tough. She can take it”

This raises the important issue of; at what point does harm to the patient warrant stopping the trial? (00:40:45 – 00:43:17)
Vivian – “I am not in isolation because I have cancer, because I have a tumor the size of a grapefruit. No. I am in isolation because I am being treated for cancer. My treatment imperils my health. Here lies the paradox.”
Clinical trials of this nature seek to establish the upper thresholds of clinical tolerance and maximum response to the treatment. It is important to ask the question; ‘Who benefits most from the continuation of the treatment regime, Vivian or the research?’  

Dr Jason Poser (Jonathon M Woodward)

In the eyes of Vivian, suggestions that her treatment has an alternative motive is confirmed in a later scene (00:47:08 – 00:49:37); “I think they see celebrity status for themselves, upon the appearance of the journal article they will no doubt write about me. But I flatter myself. The article will not be about me, it will be about my ovaries… What we have come to think of as me, is in fact a specimen jar, just the dust jacket”. 

In a further scene, Jason cements his ambitions to become a researcher and sees being a clinician as a means to end; (00:49:42 – 00:54:20)
Jason – “How are you feeling today?”
Vivian – “Fine”
Jason – “That’s great, just great”
Vivian – “How are my fluids?”
Jason – “Pretty good. No kidney involvement yet, that’s pretty amazing with Hex and Ven.”
Vivian – “How will you know when the kidneys are involved?”
Jason – “Plenty in, not much out”
Vivian – “That simple?”
Jason – “Well. No way. Compromise kidney function is a highly complex reaction. I’m simplifying it for you.”
Vivian – “Thank you.”
Jason – “We’re supposed to.”
Vivian – “Bed-side manner”
Jason – “There’s a whole course on in med school, its required. A colossal waste of time for researchers”

The discussion goes on and Vivian asks;
Vivian – “What do you say when a patient is apprehensive and frightened?”
Jason – “Of who?”
Vivian – “Never mind”
This inability of Jason to see the fear and suffering faced by Vivian illustrates both a distinct lack of empathy and understanding and the divergence between patient care and the drive for scientific knowledge.

Professor Vivan Bearing

With Vivian becoming ever increasingly fearful and scared of the treatment and her future prospects, Susie discusses what ‘end of life‘ options she has (Please refer to the Bioethics Briefing paper for further discussion). This section of the film is also important (00:57:04 – 01:18:30). When Vivian’s heart stops do the clinicians try and revive her or do they allow her to pass away? These issues have been left to Susie, with Dr Kelekian and Jason again neglecting their patient’s needs. Decisions about the timing and nature of end of life are vulnerable to the influence of a researcher’s motives; to revive the patient would prolong their life and potentially allow the trial to continue.    

The film concludes dramatically when Jason discovers Vivian has died (01:26:25 – end). He immediately calls the resuscitation team and begins to try and revive her because “She’s research!” this is despite Vivian’s decision to have the ‘Do Not Resuscitate‘ or DNR status. Eventually Susie manages to bring proceedings to a halt. This marks a poigniant end to a sad and thought provoking film. Throughout, it provides an excellent insight into the thoughts of the patient as they go from diagnosis, to treatment and then the prospect of death as they are faced with a disastrous illness.

The film is 90 minutes long, but the development of the story means that it really ought to be seen in its entirety rather than picking a clip or two. Having said that, if time is limited, the sections suggested above serve as landmarks to highlight the main issues, and could be used to stimulate discussion or illustrate a particular point. This film would primarily benefit any potential or current medical students or persons involved in clinical trials, as well as GCSE and A level students discussing clinical drug trials. Please note the film contains strong language.  

WIT (TRILT identifier: 001C1121) was first broadcast on BBC2 at 00:25 on 4^th March 2006.