Chapter 17 - mulling the lottery of clinical trials
On my first visit to the Marsden hospital near South Kensington, I met a couple of young doctors who explained the trials for which I might be eligible. They didn't exactly line up with what I said in my last blog, and the set on offer actually changed during the day, because doctor 2 added another option to the mix, which doctor 1 hadn't known about; and that extra option is the one I have actually signed up for. After seeing doctors 1 and 2, I met big chief doctor 3, and asked him what he would do in my shoes, and he said he would join the trial that I am now joining. I'll talk about the other option later because it involved some interesting ethical questions, but let's tell you about this recommended trial. It is a trial of two monoclonal antibodies, given together, on days 1 and 8 of a 21-day cycle. The two antibodies are Ramucirumab, which may inhibit blood vessel formation, and thereby sometimes (perhaps in 1 in 5 cases) slows tumour growth; and Pembrolizumab, which may switch on the body's immune response to the cancer (but perhaps only in 1 in 20 or 1 in 10 cases). The data for these two drugs for stomach cancer is quite limited, so all claims of efficacy seem quite uncertain, but the sales pitch from the research doctors was that Ramucirumab is "just as good as the standard second-line treatment" (namely the cytotoxin Paclitaxel, which has a helpful effect in about 1 in 5 cases, which in my view is not great); and that Pembrolizumab offers the chance of remission, albeit an unknown chance, and probably quite small. ("Pem", by the way, is an Anti-PD1, which is a type of monoclonal antibody I had been told by other friends was promising, and I should look out for.)
I am wary of the natural cognitive bias of researchers towards optimism about their research targets. So my gut feeling for asking to join this study was not strong. What made the opportunity more awkward was the "buy immediately while stocks last" pressure: the "Ram+Pem" trial was available internationally, right now, and open to only 6 patients. So if there was any delay, I might not get in!
Tilting me towards joining the trial was the fact that the other trial on offer at the Marsden was a trial that would offer me only "Pem" (not "Ram"), and even then, it would offer only a 50% chance of getting "Pem", thanks to randomisation. In the other branch, the treatment would be the standard second-line cytotoxin, Paclitaxel. So if I didn't get on with joining the Ram+Pem trial, I would definitely be stuck with my only option being a trial that was rated by the experts at least to be inferior to Ram+Pem.
Tilting me in the other direction, against the trial, was the certainty that joining the trial will guzzle up time and energy and will massively constrain my diary, making travel and holidays near-impossible, all in what may prove to be my final six months of life. The trial would involve coming to the hospital roughly twice every week, once for tests, and once for treatment. (Was there any way that some of the tests could simply be done in Cambridge? No, they said.)
I think it is quite comparable to a choice between buying 10,000 lottery tickets per week (so as to get a 1 in 140 chance of winning a jackpot, after a couple of years); or not buying those tickets.
When I discussed this choice with Ramesh, our feeling was that if I was obliged, most weeks, to travel to London on two separate days per week (which is what the doctors indicated would be required) then that would be too much cost. But if the cost were one day-trip to London per week for the rest of my life, then maybe that would be a price worth paying. We made clear to the doctors and the research nurse that we would really really like to not have to travel to London twice in a week.
And we figured, "if we don't like it, we can always withdraw from the trial".
So we decided to sign me up.
And guess what? Ethical rules forbid you from signing up on the same day. So I had to travel home on the train to Cambridge. Then get back on the damn train to London first thing the next morning. And meet the helpful doctor number 1 again. And sign the consent form. Then take the train back to Cambridge. Helpful doctor number 1 did say one nice thing: she said that they had reviewed the timings and they thought that actually it would be possible for me to make just one visit to London per week for the trial. The next step would be for the research nurse to organise for me to be screened, which would involve more trips to London, for a lot of tests. I begged for these screening tests to be combined to minimise my number of trips.
Here endeth the second visit to a London hospital
I was rather disappointed that, even though I'm sure my request for combined tests had been heard and understood, what happened next was a string of single appointments. The first call was about my CT scan. [Because the Marsden's trial required a CT scan even fresher than the very recent one made in Cambridge.] I accepted the appointment, but phoned the research nurse to say, erm, is this CT scan visit going to be combined with anything else? Then I received a letter telling me to come to London for an echocardiogram on another date. I phoned the research nurse again, and she shuffled both appointments and got them to be on a single day, albeit at two hospitals in London separated by more than 1 hour's travel.
Visit number three
As I said, the hospital in Cambridge isn't eligible to carry out tests for the Marsden; but St Anthony's hospital - a private hospital in the outer spiral arm of the galaxy, is. So on Friday 26th February I took the train to London, then a Thameslink train to Sutton, then a bus with a confusing 'next stop' display, which caused me to de-bus one mile early, after which I walked the last mile. The private hospital was very plush. I got echo-cardiogrammed, and the scientist confirmed that I had a heart and that she had no objection to me joining the trial.
Visit number four
A long public-transport journey later, I was at the Marsden for the CT scan. That went smoothly, indeed I was in and out early. And so, back home, to wait for more joined up tests.
The next phonecall I received was from the clinical assessment unit who wanted to schedule my biopsy. The appointment was bang in the middle of my teaching in Cambridge. I asked if the biopsy people could talk to the research people about tweaking the date; the answer was no, this was the only slot that fitted with the required research schedule. So I cancelled and rearranged my teaching, and got on the train to London. An overnight stay was required because they wanted me to show up at 8.30am. As I was getting ready to leave on Tuesday evening, Torrin clung to my leg. I think he was playing, rather than really wanting me "not to go", but the thought of a crying Torrin clinging to my leg and not letting me go stuck with me for the next 24 hours.
Visit number five
Before going to London, I made sure that the Cambridge research gang were aware that I was having a biopsy and that they were given the chance to request some tissue to go to them too. (You might recall that my voluntary gastroscopy-biopsy for Cambridge had failed to yield any satisfactory tissue.) I turned up at the Marsden on time. I was processed steadily by lovely staff (Alex and Greg in particular): cannula in; blood samples taken; answer a checklist; move into a cubicle; change into gown; get wheeled upstairs (by a skilled porter, navigating absurdly narrow corridors); answer a checklist; stare at the wall for 20 minutes; meet the Consultant; sign the consent form; get wheeled into a cold room full of toys; wait there just long enough for my left arm (which has been aching a lot recently) to really start aching. Then the consultant carefully looked with ultrasound in my neck at the target lymph node - I didn't tell you, did I, that the biopsy this time was to be from a lymph node that is enlarged and is therefore "hopefully" cancerous. Its size is still small though - only 9mm by 18mm. And the consultant told me that his bolt gun (I can't remember the correct term) has a throw of 20-25mm! So he was very likely to be chomping adjacent tissue as well as lymph node. Then in came the research nurse to collect the samples, and she told him what size was required, and he shot me slowly four times in the neck - the second impact really gave me a jolt [he said it must have hit a nerve]. Then another long wait in the cold room, then the reverse trolley ride, then a two hour wait accompanied by radio 4 and regular heart check-ups, then I was free to go. Except just before going I thought it was a good idea to phone the research nurse and ask what their plans were and was there anything else I could do for them today?
The research nurse seemed surprised that I hadn't heard: I am due to have visits six and seven on Tuesday and Thursday of next week!
The story goes on. This is way more travelling to London than I hoped, and I am disappointed about the poor communication, but I won't complain at this point. If all goes to plan this next-Thursday visit number 7 will be the start of my experimental Ram+Pem treatment.
Once that is under our belt, I will try to enforce the "only one visit per week" rule.
In other news
As I said, my left arm has been aching a lot (typically for 20 minutes at a time). Also I have been having a perpetual feeling of numbness in my left fingers, especially the tips, and much of the time a similar feeling in my left toes. After talking to my oncologist, I think these are all just long-lasting neuropathies caused by the first cycle of EOX chemotherapy back in August.
At the same time, I have been having awful back trouble. After I helped Torrin learn to ride his bike without stabilisers, I picked up a screaming Eriska, and developed a back spasm that has lasted three weeks now, cunningly moving around the back whenever my masseuse or my physio managed to cure the spasm where it was.
And the last three weeks have been dominated not only by the bad back but also by a non-stop coughy cold.
I'm sorry this feels not a very entertaining chapter.
Let me wrap up with some movie reviews and with the clinical trial anecdote I promised earlier.
The other trial I was offered at the Marsden was a randomised open-label comparison of "Pem" with the standard second line treatment, Paclitaxel, which I could already receive in Cambridge if I wanted it; but if I were in the trial I would be obliged to travel to London every week to have the whatever it was - Pem or Paclitaxel - even if it was in fact Paclitaxel. This felt a silly thing to do - if I got randomised onto the Paclitaxel branch, what would be the point, from my selfish point of view, in travelling to London every week for a treatment I could have got with my lovely Cambridge people? I left this thought unspoken, but one of the staff in London actually voiced exactly this thought for me and said that I would be entitled to leave the study at any point and it would be quite understandable if I were to quit after the randomisation if I were randomised onto the Paclitaxel branch.
I thought it was nice of the staff-member to say this. But would it be ethical to behave in that way? [Statisticians, wanting the trial to be valid, would be horrified at the idea of a patient choosing to leave the trial after the randomisation.] Fortunately I have not had to make this decision, as it looks like I am fully enrolled in a no-randomisation trial.
Movie time!
We have been enjoying some more movies, although we have, among the good ones, chosen a couple of films so awful that we actually stopped watching them, which is not something we often do.
Here are the good ones:
On my first visit to the Marsden hospital near South Kensington, I met a couple of young doctors who explained the trials for which I might be eligible. They didn't exactly line up with what I said in my last blog, and the set on offer actually changed during the day, because doctor 2 added another option to the mix, which doctor 1 hadn't known about; and that extra option is the one I have actually signed up for. After seeing doctors 1 and 2, I met big chief doctor 3, and asked him what he would do in my shoes, and he said he would join the trial that I am now joining. I'll talk about the other option later because it involved some interesting ethical questions, but let's tell you about this recommended trial. It is a trial of two monoclonal antibodies, given together, on days 1 and 8 of a 21-day cycle. The two antibodies are Ramucirumab, which may inhibit blood vessel formation, and thereby sometimes (perhaps in 1 in 5 cases) slows tumour growth; and Pembrolizumab, which may switch on the body's immune response to the cancer (but perhaps only in 1 in 20 or 1 in 10 cases). The data for these two drugs for stomach cancer is quite limited, so all claims of efficacy seem quite uncertain, but the sales pitch from the research doctors was that Ramucirumab is "just as good as the standard second-line treatment" (namely the cytotoxin Paclitaxel, which has a helpful effect in about 1 in 5 cases, which in my view is not great); and that Pembrolizumab offers the chance of remission, albeit an unknown chance, and probably quite small. ("Pem", by the way, is an Anti-PD1, which is a type of monoclonal antibody I had been told by other friends was promising, and I should look out for.)
I am wary of the natural cognitive bias of researchers towards optimism about their research targets. So my gut feeling for asking to join this study was not strong. What made the opportunity more awkward was the "buy immediately while stocks last" pressure: the "Ram+Pem" trial was available internationally, right now, and open to only 6 patients. So if there was any delay, I might not get in!
Tilting me towards joining the trial was the fact that the other trial on offer at the Marsden was a trial that would offer me only "Pem" (not "Ram"), and even then, it would offer only a 50% chance of getting "Pem", thanks to randomisation. In the other branch, the treatment would be the standard second-line cytotoxin, Paclitaxel. So if I didn't get on with joining the Ram+Pem trial, I would definitely be stuck with my only option being a trial that was rated by the experts at least to be inferior to Ram+Pem.
Tilting me in the other direction, against the trial, was the certainty that joining the trial will guzzle up time and energy and will massively constrain my diary, making travel and holidays near-impossible, all in what may prove to be my final six months of life. The trial would involve coming to the hospital roughly twice every week, once for tests, and once for treatment. (Was there any way that some of the tests could simply be done in Cambridge? No, they said.)
I think it is quite comparable to a choice between buying 10,000 lottery tickets per week (so as to get a 1 in 140 chance of winning a jackpot, after a couple of years); or not buying those tickets.
When I discussed this choice with Ramesh, our feeling was that if I was obliged, most weeks, to travel to London on two separate days per week (which is what the doctors indicated would be required) then that would be too much cost. But if the cost were one day-trip to London per week for the rest of my life, then maybe that would be a price worth paying. We made clear to the doctors and the research nurse that we would really really like to not have to travel to London twice in a week.
And we figured, "if we don't like it, we can always withdraw from the trial".
So we decided to sign me up.
And guess what? Ethical rules forbid you from signing up on the same day. So I had to travel home on the train to Cambridge. Then get back on the damn train to London first thing the next morning. And meet the helpful doctor number 1 again. And sign the consent form. Then take the train back to Cambridge. Helpful doctor number 1 did say one nice thing: she said that they had reviewed the timings and they thought that actually it would be possible for me to make just one visit to London per week for the trial. The next step would be for the research nurse to organise for me to be screened, which would involve more trips to London, for a lot of tests. I begged for these screening tests to be combined to minimise my number of trips.
Here endeth the second visit to a London hospital
I was rather disappointed that, even though I'm sure my request for combined tests had been heard and understood, what happened next was a string of single appointments. The first call was about my CT scan. [Because the Marsden's trial required a CT scan even fresher than the very recent one made in Cambridge.] I accepted the appointment, but phoned the research nurse to say, erm, is this CT scan visit going to be combined with anything else? Then I received a letter telling me to come to London for an echocardiogram on another date. I phoned the research nurse again, and she shuffled both appointments and got them to be on a single day, albeit at two hospitals in London separated by more than 1 hour's travel.
Visit number three
As I said, the hospital in Cambridge isn't eligible to carry out tests for the Marsden; but St Anthony's hospital - a private hospital in the outer spiral arm of the galaxy, is. So on Friday 26th February I took the train to London, then a Thameslink train to Sutton, then a bus with a confusing 'next stop' display, which caused me to de-bus one mile early, after which I walked the last mile. The private hospital was very plush. I got echo-cardiogrammed, and the scientist confirmed that I had a heart and that she had no objection to me joining the trial.
Visit number four
A long public-transport journey later, I was at the Marsden for the CT scan. That went smoothly, indeed I was in and out early. And so, back home, to wait for more joined up tests.
The next phonecall I received was from the clinical assessment unit who wanted to schedule my biopsy. The appointment was bang in the middle of my teaching in Cambridge. I asked if the biopsy people could talk to the research people about tweaking the date; the answer was no, this was the only slot that fitted with the required research schedule. So I cancelled and rearranged my teaching, and got on the train to London. An overnight stay was required because they wanted me to show up at 8.30am. As I was getting ready to leave on Tuesday evening, Torrin clung to my leg. I think he was playing, rather than really wanting me "not to go", but the thought of a crying Torrin clinging to my leg and not letting me go stuck with me for the next 24 hours.
Visit number five
Before going to London, I made sure that the Cambridge research gang were aware that I was having a biopsy and that they were given the chance to request some tissue to go to them too. (You might recall that my voluntary gastroscopy-biopsy for Cambridge had failed to yield any satisfactory tissue.) I turned up at the Marsden on time. I was processed steadily by lovely staff (Alex and Greg in particular): cannula in; blood samples taken; answer a checklist; move into a cubicle; change into gown; get wheeled upstairs (by a skilled porter, navigating absurdly narrow corridors); answer a checklist; stare at the wall for 20 minutes; meet the Consultant; sign the consent form; get wheeled into a cold room full of toys; wait there just long enough for my left arm (which has been aching a lot recently) to really start aching. Then the consultant carefully looked with ultrasound in my neck at the target lymph node - I didn't tell you, did I, that the biopsy this time was to be from a lymph node that is enlarged and is therefore "hopefully" cancerous. Its size is still small though - only 9mm by 18mm. And the consultant told me that his bolt gun (I can't remember the correct term) has a throw of 20-25mm! So he was very likely to be chomping adjacent tissue as well as lymph node. Then in came the research nurse to collect the samples, and she told him what size was required, and he shot me slowly four times in the neck - the second impact really gave me a jolt [he said it must have hit a nerve]. Then another long wait in the cold room, then the reverse trolley ride, then a two hour wait accompanied by radio 4 and regular heart check-ups, then I was free to go. Except just before going I thought it was a good idea to phone the research nurse and ask what their plans were and was there anything else I could do for them today?
The research nurse seemed surprised that I hadn't heard: I am due to have visits six and seven on Tuesday and Thursday of next week!
The story goes on. This is way more travelling to London than I hoped, and I am disappointed about the poor communication, but I won't complain at this point. If all goes to plan this next-Thursday visit number 7 will be the start of my experimental Ram+Pem treatment.
Once that is under our belt, I will try to enforce the "only one visit per week" rule.
In other news
As I said, my left arm has been aching a lot (typically for 20 minutes at a time). Also I have been having a perpetual feeling of numbness in my left fingers, especially the tips, and much of the time a similar feeling in my left toes. After talking to my oncologist, I think these are all just long-lasting neuropathies caused by the first cycle of EOX chemotherapy back in August.
At the same time, I have been having awful back trouble. After I helped Torrin learn to ride his bike without stabilisers, I picked up a screaming Eriska, and developed a back spasm that has lasted three weeks now, cunningly moving around the back whenever my masseuse or my physio managed to cure the spasm where it was.
And the last three weeks have been dominated not only by the bad back but also by a non-stop coughy cold.
I'm sorry this feels not a very entertaining chapter.
Let me wrap up with some movie reviews and with the clinical trial anecdote I promised earlier.
The other trial I was offered at the Marsden was a randomised open-label comparison of "Pem" with the standard second line treatment, Paclitaxel, which I could already receive in Cambridge if I wanted it; but if I were in the trial I would be obliged to travel to London every week to have the whatever it was - Pem or Paclitaxel - even if it was in fact Paclitaxel. This felt a silly thing to do - if I got randomised onto the Paclitaxel branch, what would be the point, from my selfish point of view, in travelling to London every week for a treatment I could have got with my lovely Cambridge people? I left this thought unspoken, but one of the staff in London actually voiced exactly this thought for me and said that I would be entitled to leave the study at any point and it would be quite understandable if I were to quit after the randomisation if I were randomised onto the Paclitaxel branch.
I thought it was nice of the staff-member to say this. But would it be ethical to behave in that way? [Statisticians, wanting the trial to be valid, would be horrified at the idea of a patient choosing to leave the trial after the randomisation.] Fortunately I have not had to make this decision, as it looks like I am fully enrolled in a no-randomisation trial.
Movie time!
We have been enjoying some more movies, although we have, among the good ones, chosen a couple of films so awful that we actually stopped watching them, which is not something we often do.
Here are the good ones:
| Heist (Gene Hackman) is a film I have seen before but I had forgotten almost all of it. It was a good film. Perhaps an implausible final relationship twist at the end, but lots of nice content along the way. I love heist films. | ☆☆☆ |
| The Martian - very well made, and a nice film about science. The one bit I couldn't believe was (in the final act) that Matt Damon would be able to steer his specially-pierced jet-suit without setting himself spinning; and then I couldn't imagine how he could have used his jet to cancel the spin, without producing another unwanted spin. | ☆☆☆☆ |
| A nice realistic film was Enough Said, which in spite of being set in Los Angeles was quite watchable. Most of the main characters are female, and the director was female too. | ☆☆☆ |
3 comments:
So sorry about the many trips to London. Would you be interested in having a volunteer driver drive you sometimes, or would you worry about the CO2 and other emissions?
All the best with the trial.
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