Ben Goldacre of badscience.net writes about a weird and wonderful collation of studies reporting the placebo response in Bad Science (see standard preamble). Most of his discussions or descriptions of these studies are helpful and illuminating but it looked implausible that anyone would be able to comment on all of the literature cited within it.
It had caught my attention as it had made me wonder if I should be considering using intramuscular injections painkillers more often. The thing is – this is not a dusty academic point; potentially it has genuine clinical value to thousands of patients every day. If I visit someone with, say, severe back pain should I be more inclined toward giving them a more invasive treatment purely for the additional placebo effect eg an intramuscular injection of a non-steroidal (NSAID) painkiller?
Seemingly, both Northern Doctor and Bandolier’s Little Book of Making Sense of the Medical Evidence somewhat dissent from Goldacre. However, as I don’t have access to either the Bandolier book or the full paper (de Craen et al, pg 69 (2000) ref below), I’m not in any position to comment.
However, Northern Doctor’s comments are a serious appraisal of one point and may be relevant to a wider discussion of placebo. They also highlight the uneasy hybridisation of Bad Science as a popular science book which also has a passing resemblance to a digest of research findings (on some topics) to a readership that has some specialist knowledge. Northern Doctor is fairly forgiving of this and remarks:
I am sure that there was a desire to keep the book as accessible and non-threatening as possible – perhaps this relates to the suggestion that somehow science is a bit dirty, a bit elitist and should be hidden away. So I think I can guess why there is not an index and the referencing is half-hearted.
Although HolfordWatch has not reviewed Bad Science, it has a related discussion: Ben Goldacre and Placebo (Part 2) Radio 4: Lacking In Cheese or Missing An Eye.
HolfordWatch mentions: Cochrane review that concluded that there is little evidence to support ‘a large effect for the placebo response’. HolfordWatch provides several other references that (implicitly) discuss some of the differences between the papers that met the inclusion criteria for the Cochrane review and those such as the studies that Goldacre cites. There is some discussion of other effects and biases that might influence the placebo response.
Chapter 5, The Placebo Effect is lively and well-argued. I’m not sure how much more discussion of other papers and findings could have been included without altering the balance of the book and changing its tone: the complexity of the issues involved in giving a fair overview of the state of the research is probably one of the reasons why several writers (popular as well as academic) have dedicated entire books to the placebo response. However, it would have been good to read an acknowledgement of the dissenting voices. There are researchers who find ‘little evidence in general for powerful placebo effects’ and who argue that ‘there is no justification for offering placebos outside a clinical setting‘.
I was drawing together a list of the references when I realised that it was not practical to review this chapter. Therefore, below, I’ve posted links to the references in the book (where I could find them) and links to some partial reviews of Goldacre’s handling of the placebo response (I will update the links to include more if I find them).
In several places, Goldacre makes a plausible argument that homeopathy is an ideal intervention to test the value of a therapeutic encounter.
[H]omeopaths want to believe that the power is in the pill, rather than in the whole process of going to visit a homeopath, having a chat, and so on. It is crucially important to their professional identity. But I believe that going to see a homeopath is probably a helpful intervention, in some cases, for some people, even if the pills are just placebos. I think some patients would agree, and I think that this would be an interesting thing to measure. It would be easy, and you would do something called a “waiting list controlled trial”. [pg 58 Bad Science]
In this, Goldacre seems to be acknowledging the range of people who may function as ‘therapeutic agents’ in particular contexts. Houston (1938) wrote: “the placebo has always been the norm of medical practice” arguing that, doctors themselves, were
the therapeutic agent by which cures were effected. Their therapeutic procedures, whether they were inert or whether they were dangerous, were placebos, symbols by which their patients’ faith and their own was sustained.
Overall, I understand that Goldacre is enchanted by the placebo response and has probably been longing to write an extended brain dump of why it is so weird and intriguing. However, in the absence of any acknowledgement that there is some dispute concerning the effectiveness of the placebo outside particular settings, it does look like a partial presentation of the overall literature. As the reader, I’m not surprised to find it’s all a little bit more complicated than that.
References from Bad Science: Chapter 5, The Placebo Effect
pg 63 ‘Shall [the placebo]': Editorial. The Placebo in Medicine. Medical Press, 18 June 1890: 642.
pg 64 ‘Henry Beecher': Beecher HK. The powerful placebo. JAMA. 1955 Dec 24;159(17):1602-6.
pg 64 ‘Peter Parker': Skrabanek P, McCormick J. Fads and Fallacies in Medicine. Amherst, NY: Prometheus Books; 1990.
pg 66 ‘Daniel Moerman': Moerman DE. General Medical Effectiveness and Human Biology: Placebo Effects in the Treatment of Ulcer Disease. Medical Anthropology Quarterly (Aug., 1983); Vol. 14, No. 4: 3-16.
pg 67 ‘in a different dataset': de Craen AJ, Moerman DE, Heisterkamp SH, Tytgat GN, Tijssen JG, Kleijnen J. Placebo effect in the treatment of duodenal ulcer. Br J Clin Pharmacol. Dec 1999;48(6):853-60.
pg 68 ‘Blackwell ': Blackwell B, Bloomfield SS, Buncher CR. Demonstration to medical students of placebo responses and non-drug factors. Lancet. (10 Jun 1972); 1(7763):1279-82.
pg 68 ‘Another study': Schapira K, McClelland HA, Griffiths NR, Newell DJ. Study on the effects of tablet colour in the treatment of anxiety states. BMJ. (23 May 1970);1 (5707):446-9.
pg 68 ‘a survey of the colour': de Craen AJ, Roos PJ, Leonard de Vries A, Kleijnen J. Effect of colour of drugs: systematic review of perceived effect of drugs and of their effectiveness. BMJ. (21-28 Dec 1996); 313(7072):1624-6.
pg 68 ‘In 1970′: Hussain MZ, Ahad A. Tablet colour in anxiety states. BMJ. (22 Aug 1970); 3(5720):466.
pg 69 ‘Route of administration':
- Grenfell RF, Briggs AH, Holland WC. A double blind study of the treatment of hypertension. JAMA. (1961) 176:124–128.
- de Craen AJM, Tijssen JGP, de Gans J, Kleijnen J. Placebo effect in the acute treatment of migraine: subcutaneous placebos are better than oral placebos. J Neur (2000); 247:183–188.
- Gracely RH, Dubner R, McGrath PA. Narcotic analgesia: fentanyl reduces the intensity but not the unpleasantness of painful tooth pulp sensations. Science. (Mar 23, 1979); 203 (4386): 1261-3.
pg 69 ‘the bizarre story of packaging': Kaptchuk TJ, Stason WB, Davis RB, Legedza AR, Schnyer RN, Kerr CE, Stone DA, Nam BH, Kirsch I, Goldman RH. Sham device v inert pill: randomised controlled trial of two placebo treatments. BMJ. (18 Feb 2006); 332 (7538): 391-7.
pg 69 ‘Branthwaite and Cooper': Branthwaite A, Cooper P. Analgesic effects of branding in treatment of headaches. BMJ (Clin Res Ed). 1981; 282: 1576-8.
pg 70 ‘a recent study': Waber RL, Shiv B, Carmon Z, Ariely D. Commercial features of placebo and therapeutic efficacy. JAMA. (5 Mar 2008); 299(9): 1016-7.
pg 70 ‘a paper currently in press': Gino F. Do we listen to advice just because we paid for it? The impact of advice cost on its use. Organizational Behavior and Human Decision Processes. (28 Nov 2008); 107(2): 234-245. doi:10.1016/j.obhdp.2008.03.001
pg 70 ‘Montgomery and Kirsch': Montgomery GH, Kirsch I. Mechanisms of placebo pain reduction: An empirical investigation. Psych Science (1996) 7: 174–6.
pg 71 ‘a placebo-controlled trial': Cobb LA, Thomas GI, Dillard DH, Merendino KA, Bruce RA. An evaluation of internal-mammary-artery ligation by a double-blind technic. NEJM. (28 May 1959); 260(22): 1115-8.
pg 72 ‘A Swedish study': Linde C, Gadler F, Kappenberger L, Rydén L. Placebo effect of pacemaker implantation in obstructive hypertrophic cardiomyopathy. PIC Study Group. Pacing In Cardiomyopathy. Am J Cardiol. (15 Mar 1999; 83(6): 903-7.
pg 72 ‘Electrical machines have': Johnson AG. Surgery as a placebo. Lancet. (22 Oct 1994); 344 (8930): 1140-2.
pg 72 ‘an elegant study': Crum AJ, Langer EJ. Mind-set matters: exercise and the placebo effect. Psych Science. (Online 5 Apr 2007); 18(2); 165-71.
pg 73 ‘Gryll and Katahn': Gryll SL, Katahn M. Situational factors contributing to the placebos effect. Psychopharmacology (Berl). (1978); 57: 253-61.
pg 74 ‘Gracely ': Gracely RH, Dubner R, Deeter WR, Wolskee PJ. Clinicians’ expectations influence placebo analgesia. Lancet. (5 Jan 1985); 1(8419): 43.
pg 75 ‘In 1987, Thomas': Thomas KB. General practice consultations: is there any point in being positive? BMJ (Clin Res Ed). (9 May 1987); 294 (6581): 1200-2.
pg 76 ‘Raymond Tallis': Tallis R. Hippocratic Oaths: Medicine and its discontents. London, Atlantic. 2004.
pg 77 ‘Quesalid': Lévi-Strauss C. The Sorcerer and His Magic. In Structural Anthropology. (trans Jacobson C, Schoef BG.) Basic Books (1963).
pg 78 ‘a classic study from 1965′: Park LC, Covi L. Nonblind Placebo Trial: an exploration of neurotic patients’ responses to placebo when its inert content is disclosed. Arch Gen Psychiatry. (Apr 1965); 12: 36-45.
pg 78 ‘Dr Stewart Wolf': Wolf S. Effects of suggestion and conditioning on the action of chemical agents in human subjects; the pharmacology of placebos. J Clin Invest. (Jan 1950); 29(1):100-9.
pg 79 ‘It’s been shown': de la Fuente-Fernández R, Ruth TJ, Sossi V, Schulzer M, Calne DB, Stoessl AJ. Expectation and dopamine release: mechanism of the placebo effect in Parkinson’s disease. Science. (10 Aug 2001); 293 (5532): 1164-6.
pg 79 ‘Zubieta ': Zubieta JK, Bueller JA, Jackson LR, Scott DJ, Xu Y, Koeppe RA, Nichols TE, Stohler CS. Placebo effects mediated by endogenous opioid activity on mu-opioid receptors. J Neurosci. (24 Aug 2005); 25 (34): 7754-62.
pg 80 ‘Researchers have measured': Ader R, Cohen N. Behaviorally conditioned immunosuppression. Psychosom Med. ( Jul-Aug 1975); 37(4): 333-40.
pg 80 ‘researchers gave healthy': Goebel MU, Trebst AE, Steiner J, Xie YF, Exton MS, Frede S, Canbay AE, Michel MC, Heemann U, Schedlowski M. Behavioral conditioning of immunosuppression is possible in humans. FASEB J. (Dec 2002); 16(14): 1869-73.
pg 80 ‘Researchers have even': Buske-Kirschbaum A, Kirschbaum C, Stierle H, Lehnert H, Hellhammer D. Conditioned increase of natural killer cell activity (NKCA) in humans. Psychosom Med. (Mar-Apr 1992); 54(2): 123-32.
pg 80 ‘From survey data': Goodwin JS, Goodwin JM, Vogel AV. Knowledge and use of placebos by house officers and nurses. Ann Intern Med. (Jul 1979); 91(1): 106-10.
pg 80 ‘You are a placebo responder': Meaning, Medicine and the ‘Placebo Effect’ by Moerman DE, Cambridge University Press, 2002, p. 34, summarising references to five further studies.
pg 81 ‘one of the most impressive': Moerman DE, Harrington A. Making space for the placebo effect in pain medicine. Seminars in Pain Medicine. (Mar 2005); 3(1 Spec Issue) :2-6.
pg 81 ‘another study from 2002′: Walsh BT, Seidman SN, Sysko R, Gould M. Placebo response in studies of major depression: variable, substantial, and growing. JAMA. (10 Apr 2002); 287(14): 1840-7.
pg 84 ‘one study found': Schmidt K, Ernst E. Aspects of MMR. Survey shows that some homoeopaths and chiropractors advise against MMR. BMJ. (Sep 14 2002); 325(7364): 597.
References in post
Houston WR. The Doctor Himself as a Therapeutic Agent. Annals of Internal Medicine. (Feb 1938); 11, 1416-25.