On 2014 Feb 23, David Keller commented:

A new approach or a step backward?

The "new approach" to disease-modifying drug trials seems to me to be a step backwards. Due to the inability to obtain placebo Byetta pen-injectors, the study was conducted without a true placebo control. Instead, the intervention group self-injected with actual Byetta pen-injectors daily, while the comparison group did nothing special and was followed passively over time. Thus, there was no control for the powerful placebo effect caused by daily self-injection by the intervention group, which could account for much of the beneficial effect observed. The symptoms of Parkinson disease are known to be somewhat dependent on the psychological state and mood of the patient, which tends to magnify the placebo effect.

A recent meta-analysis found that Parkinson patients treated with active drug had significantly less objectively measured motor response to the same intervention if they knew there was a chance that they were receiving placebo, even with effective double blinding (1). This decreased response, dubbed "the lessebo effect", could account for up to 4.1 UPDRS units of motor improvement for patients in studies lacking double-blinded placebo controls.

The manufacturer of Byetta should be encouraged to donate Byetta pen-injectors filled with normal saline to future clinical trials of exenatide, allowing them to be conducted as proper placebo-controlled and double-blinded studies. If such future trials demonstrate benefits, their results can be interpreted without caveats, and Byetta's manufacturer can expect to be repaid for their support of medical science by the subsequent increased sales to non-diabetic Parkinson patients.

Reference

1) Mestre TA, Shah P, Marras C, Tomlinson G, Lang AE. Another face of placebo: The lessebo effect in Parkinson disease: Meta-analyses. Neurology. 2014 Apr 22;82(16):1402-9. doi: 10.1212/WNL.0000000000000340. Epub 2014 Mar 21. PubMed PMID: 24658930; PubMed Central PMCID: PMC4001195.

On 2014 Feb 23, David Keller commented:

A new approach or a step backward?

The "new approach" to disease-modifying drug trials seems to me to be a step backwards. Due to the inability to obtain placebo Byetta pen-injectors, the study was conducted without a true placebo control. Instead, the intervention group self-injected with actual Byetta pen-injectors daily, while the comparison group did nothing special and was followed passively over time. Thus, there was no control for the powerful placebo effect caused by daily self-injection by the intervention group, which could account for much of the beneficial effect observed. The symptoms of Parkinson disease are known to be somewhat dependent on the psychological state and mood of the patient, which tends to magnify the placebo effect.

A recent meta-analysis found that Parkinson patients treated with active drug had significantly less objectively measured motor response to the same intervention if they knew there was a chance that they were receiving placebo, even with effective double blinding (1). This decreased response, dubbed "the lessebo effect", could account for up to 4.1 UPDRS units of motor improvement for patients in studies lacking double-blinded placebo controls.

The manufacturer of Byetta should be encouraged to donate Byetta pen-injectors filled with normal saline to future clinical trials of exenatide, allowing them to be conducted as proper placebo-controlled and double-blinded studies. If such future trials demonstrate benefits, their results can be interpreted without caveats, and Byetta's manufacturer can expect to be repaid for their support of medical science by the subsequent increased sales to non-diabetic Parkinson patients.

Reference

1) Mestre TA, Shah P, Marras C, Tomlinson G, Lang AE. Another face of placebo: The lessebo effect in Parkinson disease: Meta-analyses. Neurology. 2014 Apr 22;82(16):1402-9. doi: 10.1212/WNL.0000000000000340. Epub 2014 Mar 21. PubMed PMID: 24658930; PubMed Central PMCID: PMC4001195.