A Ghostwriter Speaks

PLoS ONE offers the confessions of a former medical ghostwriter: Being the Ghost in the Machine.





The article (which is open access and short, so well worth a read) explains how Linda Logdberg became a medical writer; what excited her about the job; what she actually did; and what made her eventually give it up.



Ghostwriting of course has a bad press at the moment and it's recently been banned by some leading research centres. Ghostwriting certainly is concerning, because of what it implies about the process leading up the publication.



However, it doesn't create bad science. A bad paper is bad because of what it says, not because of who (ghost)wrote it. Real scientists can write bad papers without a ghostwriter's help.



When pharmaceutical companies pay a ghostwriter, they are not doing this to get access to special dark arts that real scientists are innocent of. As far as I can see, it's just more efficient to use a specialist writer to do your scientific sins, when you're doing it all the time.



Rather like every evil sorcerer has an apprentice to do the day-to-day work of sacrificing animals and mixing potions.



Logdberg says:

My career came to an end over a job involving revising a manuscript supporting the use of a drug for attention deficit-hyperactivity disorder (ADHD), with a duration of action that fell between that of shorter- and longer-acting formulations.



However, I have two children with ADHD, and I failed to see the benefit of a drug that would wear off right at suppertime, rather than a few hours before or a few hours after. Suppertime is a time in ADHD households when tempers and homework arguments are often at their worst.



...Attempts to discuss my misgivings with the [medical] contact met with the curt admonition to ‘‘just write it.’’ But perhaps because this particular disorder was so close to home, I was unwilling to turn this ugly duckling of a ‘‘me-too’’ drug into a marketable swan.

Many scientists will recall being in that kind of situation, albeit in a different context.



When writing a grant application, for example, you are almost literally trying to sell your proposed research to the awarding committee, on several levels. You need to sell the importance of the scientific question; the likely practical benefits of the research; the chance of success using your methods; what makes you the right person to do this work, and so on.



Writing a paper is much the same, although in this case you're selling research you've already done, and the data you collected.



Turning ugly ducklings into fundable, or publishable, swans, is part and parcel of modern science. Of course, the ducklings are not always as ugly as in the case Logdberg describes, but they are rarely as beautiful as they eventually end up.



Logdberg, L. (2011). Being the Ghost in the Machine: A Medical Ghostwriter's Personal View PLoS Medicine, 8 (8) DOI: 10.1371/journal.pmed.1001071

A Ghostwriter Speaks

PLoS ONE offers the confessions of a former medical ghostwriter: Being the Ghost in the Machine.





The article (which is open access and short, so well worth a read) explains how Linda Logdberg became a medical writer; what excited her about the job; what she actually did; and what made her eventually give it up.



Ghostwriting of course has a bad press at the moment and it's recently been banned by some leading research centres. Ghostwriting certainly is concerning, because of what it implies about the process leading up the publication.



However, it doesn't create bad science. A bad paper is bad because of what it says, not because of who (ghost)wrote it. Real scientists can write bad papers without a ghostwriter's help.



When pharmaceutical companies pay a ghostwriter, they are not doing this to get access to special dark arts that real scientists are innocent of. As far as I can see, it's just more efficient to use a specialist writer to do your scientific sins, when you're doing it all the time.



Rather like every evil sorcerer has an apprentice to do the day-to-day work of sacrificing animals and mixing potions.



Logdberg says:

My career came to an end over a job involving revising a manuscript supporting the use of a drug for attention deficit-hyperactivity disorder (ADHD), with a duration of action that fell between that of shorter- and longer-acting formulations.



However, I have two children with ADHD, and I failed to see the benefit of a drug that would wear off right at suppertime, rather than a few hours before or a few hours after. Suppertime is a time in ADHD households when tempers and homework arguments are often at their worst.



...Attempts to discuss my misgivings with the [medical] contact met with the curt admonition to ‘‘just write it.’’ But perhaps because this particular disorder was so close to home, I was unwilling to turn this ugly duckling of a ‘‘me-too’’ drug into a marketable swan.

Many scientists will recall being in that kind of situation, albeit in a different context.



When writing a grant application, for example, you are almost literally trying to sell your proposed research to the awarding committee, on several levels. You need to sell the importance of the scientific question; the likely practical benefits of the research; the chance of success using your methods; what makes you the right person to do this work, and so on.



Writing a paper is much the same, although in this case you're selling research you've already done, and the data you collected.



Turning ugly ducklings into fundable, or publishable, swans, is part and parcel of modern science. Of course, the ducklings are not always as ugly as in the case Logdberg describes, but they are rarely as beautiful as they eventually end up.



Logdberg, L. (2011). Being the Ghost in the Machine: A Medical Ghostwriter's Personal View PLoS Medicine, 8 (8) DOI: 10.1371/journal.pmed.1001071

Do We Need Placebos?

A news feature in Nature asks whether placebo controls are always a good idea: Why Fake It?



The piece looks at experimental neurosurgical treatments for Parkinson's, such as "Spheramine". This consists of cultured human cells, which are implanted directly into the brain of the sufferer. The idea is that the cells will grow and help produce dopamine, which is deficient in Parkinson's.



Peggy Willocks, a 44 year old teacher, took part in a trial of the surgery in 2000. She says it helped stave off the symptoms for years, but the development of Spheramine was axed in 2008 after a controlled trial found it didn't work any better than a placebo.



The placebo was "sham surgery" i.e. putting the patient through a full surgical procedure, and making holes in their skull, but without doing anything to their brain.



It's cheap and easy to do a placebo controlled trial of a drug - all you need is a sugar pill. But with neurosurgery, it's clearly a lot more involved. A placebo has to be believable. Convincing sham surgery is expensive, time-consuming, and it has real risks, albeit small ones.



Is it ethical to put patients through that?



That, I think, can only be decided on a trial-by-trial basis. It depends on the likely benefits of the treatment, and whether the trial is scientifically sound. Obviously, it'd be wrong to do sham surgery as part of a flawed trial that won't tell us anything useful.



The Nature article, however, goes further than this, and suggests that placebo controlled trials may be unsuitable for testing these kinds of treatments, failing to detect a real benefit in some patients:

There are hints from some of the failed phase II trials that patients followed up beyond study endpoints might tell a more positive story. Some say, therefore, that sham controls are sinking the prospects of valuable drugs.



Anders Björklund, a neuroscientist at Lund University in Sweden who is collaborating with [Roger Barker of Cambridge], says that sham surgery can lead researchers to throw out a strategy prematurely if the trial fails because of technical or methodological glitches rather than a true lack of efficacy.

A patient advocate agrees:

According to Perry Cohen, who leads a network of patient activists called the Parkinson Pipeline Project, that’s exactly what is happening. He had always questioned the need for sham surgery, he says, but after the string of phase II failures, “We started saying, ‘Hey, this is a problem. These trials failed, but we know they are working for some people.’”

...Cohen [says] that patients have different priorities and that researchers must take these into account. Researchers use placebo controls to weed out false positives. But for patients, the real ogre is the false negatives — which can sink a therapy before it has been optimized.

I'm not sure about this. If I had Parkinson's, I would certainly hate to miss out on the genuine cure because a trial had failed to recognize that it worked. But equally, I would not be happy to be given a rubbish treatment that would have failed a placebo controlled trial, but never got one, because of arguments like this.



Placebo controlled trials can fail to detect benefits if they are too short, too small, methodologically flawed, or whatever. Certainly, a trial can be placebo controlled, and still crap. But the answer is surely to do better trials, not no trials.



It may well be that we shouldn't rush to do placebo controlled trials until later in the development process, when the technique has been properly refined. But the history of medicine is littered with treatments that "we know work for some people" - that didn't.



Katsnelson, A. (2011). Experimental therapies for Parkinson's disease: Why fake it? Nature, 476 (7359), 142-144 DOI: 10.1038/476142a

Do We Need Placebos?

A news feature in Nature asks whether placebo controls are always a good idea: Why Fake It?



The piece looks at experimental neurosurgical treatments for Parkinson's, such as "Spheramine". This consists of cultured human cells, which are implanted directly into the brain of the sufferer. The idea is that the cells will grow and help produce dopamine, which is deficient in Parkinson's.



Peggy Willocks, a 44 year old teacher, took part in a trial of the surgery in 2000. She says it helped stave off the symptoms for years, but the development of Spheramine was axed in 2008 after a controlled trial found it didn't work any better than a placebo.



The placebo was "sham surgery" i.e. putting the patient through a full surgical procedure, and making holes in their skull, but without doing anything to their brain.



It's cheap and easy to do a placebo controlled trial of a drug - all you need is a sugar pill. But with neurosurgery, it's clearly a lot more involved. A placebo has to be believable. Convincing sham surgery is expensive, time-consuming, and it has real risks, albeit small ones.



Is it ethical to put patients through that?



That, I think, can only be decided on a trial-by-trial basis. It depends on the likely benefits of the treatment, and whether the trial is scientifically sound. Obviously, it'd be wrong to do sham surgery as part of a flawed trial that won't tell us anything useful.



The Nature article, however, goes further than this, and suggests that placebo controlled trials may be unsuitable for testing these kinds of treatments, failing to detect a real benefit in some patients:

There are hints from some of the failed phase II trials that patients followed up beyond study endpoints might tell a more positive story. Some say, therefore, that sham controls are sinking the prospects of valuable drugs.



Anders Björklund, a neuroscientist at Lund University in Sweden who is collaborating with [Roger Barker of Cambridge], says that sham surgery can lead researchers to throw out a strategy prematurely if the trial fails because of technical or methodological glitches rather than a true lack of efficacy.

A patient advocate agrees:

According to Perry Cohen, who leads a network of patient activists called the Parkinson Pipeline Project, that’s exactly what is happening. He had always questioned the need for sham surgery, he says, but after the string of phase II failures, “We started saying, ‘Hey, this is a problem. These trials failed, but we know they are working for some people.’”

...Cohen [says] that patients have different priorities and that researchers must take these into account. Researchers use placebo controls to weed out false positives. But for patients, the real ogre is the false negatives — which can sink a therapy before it has been optimized.

I'm not sure about this. If I had Parkinson's, I would certainly hate to miss out on the genuine cure because a trial had failed to recognize that it worked. But equally, I would not be happy to be given a rubbish treatment that would have failed a placebo controlled trial, but never got one, because of arguments like this.



Placebo controlled trials can fail to detect benefits if they are too short, too small, methodologically flawed, or whatever. Certainly, a trial can be placebo controlled, and still crap. But the answer is surely to do better trials, not no trials.



It may well be that we shouldn't rush to do placebo controlled trials until later in the development process, when the technique has been properly refined. But the history of medicine is littered with treatments that "we know work for some people" - that didn't.



Katsnelson, A. (2011). Experimental therapies for Parkinson's disease: Why fake it? Nature, 476 (7359), 142-144 DOI: 10.1038/476142a