Are Placebo’s Getting More Effective?

At least some people believe they are – particularly those drug companies whose pipeline champions are being sunk by the famous effect. This Wired article offers a great list of drugs recently entombed by the placebo effect. It also explains it’s history and the concern it is causing in drug development. But I disagree that the placebo effect is ‘increasing’ as they suggest.

The drop in drug approvals they cite and many of the specific examples they give are probably not due to an ‘increasing placebo effect’ but poor trial design, less effective new therapies and the lack of low hanging fruit. I would even suggest that the perceived change in the effectiveness of Prozac is actually the result of better experimental measurement leading to better data that demonstrates what clinicians have always known.

Trials are becoming harder to design as there is less money available – in part because potential profits from new drugs are not what they used to be. Studies are ‘powered’ at an absolute minimum, and resources sent offshore to clinics with high capacity but lower quality guarantees. This is of particular concern in studies where drug efficacy is highly dependant on patient or clinician reporting rather than hard measures such as well defined lab tests. They Merck scientist in fact demonstrates this when he says they saw different effects in Spain and France.

They author also fails to mention that many new drugs being trialled are in therapeutic areas fairly well served by existing drugs. there is less room for improvement and therefore it is harder to create more efficacious drugs. Early phase testing is easily misleading due to small sample size and other biases.

When the article delves into the cognitive neuroscience behind the placebo effect they indeed point to the fact that by definition, the placebo effect can’t ‘increase’ unless the human brain changed substantially in the last 40 years.

Despite this it is a great article and I look forward to hearing more about the Placebo Response Drug Trials Survey.

Clinical Trials Evolving

A NYTimes article, Lack of Study Volunteers Is Said To Hobble Fight Against Cancer, gives some stark statistics about the diminishing availability of patients for cancer trials, and hints at some of the broader problems in the world of clinical trials.

At a recent NHMRC Clinical Trials  meeting, several presentations dealt with the changing nature of clinical trials. The main challenges presented were:

1. Trials are being moved by companies to developing countries where trials costs are cheaper and more patients available.
2. Fewer trials are for drugs that will demonstrate significant improvements in efficacy. This in turn means larger numbers of patients are needed for the trial to demonstrate superiority.
3. New technology, particularly biomarkers, are both a benefit and a challenge as subpopulations of responders are identified and trials endpoints need to be shifted.

Overall, the feeling was that the current trial paradigm is far to rigid and expensive. The NYTimes article alludes to this strongly. One impressive stat they cite was that there are more than 6,500 cancer clinical trials seeking adult patients, according to clinicaltrials.gov. But more than one trial in five sponsored by the US National Cancer Institute failed to enroll a single subject, and only half reached the minimum needed for a meaningful result (reported in a recent review in The Oncologist). At California Cancer Care, in Greenbrae, north of San Francisco, they try to offer trials to every patient. Yet last year they enrolled just 43 of about 700 new patients.

While the US has it’s own health care issues that are partly impacting on trial uptake, these are ominous signs – to some.

My view is that these changes are part of the new world of drug development. We are moving towards streamlined naturalistic trials in a world replete with real-time patient outcomes data. The faster we run out of pointless trials for me-too drugs, the better.