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The media is constantly in the crosshairs. Too much information, not enough information, not the right information--at times it seems like nailing jello to the wall.
A fact that our society has missed--WE are the media. All of us. Creating news, analyzing data, telling stories and consuming news--us, us, us, and us. If the answers are wrong, we need to start taking responsibility for the questions. They may be wrong too. |
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The paradox I am describing persists in medicine and even more profoundly in Alzheimer's disease research. As an outsider--non-annointed member of the press--I was relegated to observe the recent international conference from afar. Digital media--my cover for my true identity as a blogger journalist--was not exactly granted access to the Alzheimer's Association International Conference (AAIC) meeting, although not restricted from paying the exhorbant registration fee. Let's be realistic, I struggle with research published behind a pay-wall, often not within reach of those that strive to communicate findings--you can imagine how unfair it seems to selectively filter the press.
Although not welcomed into the conference I had many opportunities to network and discuss the meeting with peers and experts in Alzheimer's Disease research--more on that later.
I learned of the abstract below rather quietly from the website and knew a few colleagues that attended the session. Funny how I didn't speak to one person that believed the spin propogating in the secondary news outlets.
How hard could it be to review the findings and decipher the outcomes reported in conflicting headlines.
Although not welcomed into the conference I had many opportunities to network and discuss the meeting with peers and experts in Alzheimer's Disease research--more on that later.
I learned of the abstract below rather quietly from the website and knew a few colleagues that attended the session. Funny how I didn't speak to one person that believed the spin propogating in the secondary news outlets.
How hard could it be to review the findings and decipher the outcomes reported in conflicting headlines.
First Phase 3 Study of Tau-Targeting Drug in Alzheimer's Disease
First of all, it wasn't easy locating the actual abstract. The details are embargoed even for press but this was particularly cloak & daggerish for my taste.
Phase 3 Trial of the Tau Aggregation Inhibitor Leuco-Methylthioninium-Bis(hydromethanesulfonate) (LMTM) in Mild to Moderate Alzheimer's Disease Abstract ID: a10476
Background: Leuco-methylthioninium-bis(hydromethanesulfonate) (LMTM; TRx-0237) is a novel stabilized reduced form of the methylthioninium (MT) moiety (Harrington et al. J Biol Chem 2015;290:10862) with potential for efficacy in treatment of Alzheimer's disease (AD). A previous trial using the oxidized form of MT identified dose dependent absorption limitations (Wischik et al. J Alzheimers Dis 2015;44:705). LMTM is better absorbed and tolerated (Baddeley et al. J Pharmacol Exptl Therapeutics 2015;352:110) permitting higher doses to be tested. It acts as a selective tau aggregation inhibitor in vitro (Harrington et al. J Biol Chem 2015;290:10862) and in transgenic mouse models (Melis et al. Behav Pharmacol 2015;26:353).
Methods: The present 15-month double-blind, placebo-controlled trial (NCT01689246) was performed in patients with probable AD, Mini-Mental State Examination (MMSE) score in the range 14-26, Clinical Dementia Rating (CDR) 1-2 and age < 90 years. Patients were randomized 3:3:4 to receive oral LMTM at doses of 150 or 250 mg/day or placebo (containing 8 mg/day, to maintain blinding) respectively. Primary efficacy outcomes were change from baseline on cognitive (Alzheimer's Disease Assessment Scale cognitive subscale; ADAS-Cog) and functional (Alzheimer's Disease Cooperative Study Activities of Daily Living; ADCS-ADL) scores. Three-monthly assessment included magnetic resonance imaging (MRI) as a disease modifying outcome. Other secondary outcomes included ADCS-CGIC and MMSE.
Results: A total of 891 patients were randomized, of whom 62% were female. Approved AD treatments were being taken in 85%. The mean age was 70.6 (SD 9.0) years and baseline MMSE score was 18.7 (SD 3.4). Dementia was of moderate severity (MMSE score 14-19) in 61%. The study efficacy and safety outcomes will be reported.
Conclusions: The outcomes of this phase 3 trial will highlight the potential therapeutic value of tau aggregation inhibitor therapy in AD. A second phase 3 trial of LMTM for AD will be completed and reported later in 2016.
Methods: The present 15-month double-blind, placebo-controlled trial (NCT01689246) was performed in patients with probable AD, Mini-Mental State Examination (MMSE) score in the range 14-26, Clinical Dementia Rating (CDR) 1-2 and age < 90 years. Patients were randomized 3:3:4 to receive oral LMTM at doses of 150 or 250 mg/day or placebo (containing 8 mg/day, to maintain blinding) respectively. Primary efficacy outcomes were change from baseline on cognitive (Alzheimer's Disease Assessment Scale cognitive subscale; ADAS-Cog) and functional (Alzheimer's Disease Cooperative Study Activities of Daily Living; ADCS-ADL) scores. Three-monthly assessment included magnetic resonance imaging (MRI) as a disease modifying outcome. Other secondary outcomes included ADCS-CGIC and MMSE.
Results: A total of 891 patients were randomized, of whom 62% were female. Approved AD treatments were being taken in 85%. The mean age was 70.6 (SD 9.0) years and baseline MMSE score was 18.7 (SD 3.4). Dementia was of moderate severity (MMSE score 14-19) in 61%. The study efficacy and safety outcomes will be reported.
Conclusions: The outcomes of this phase 3 trial will highlight the potential therapeutic value of tau aggregation inhibitor therapy in AD. A second phase 3 trial of LMTM for AD will be completed and reported later in 2016.
Still not much here to be creating the frenzy that caught my eye in at least one or two hopeful headlines. Efficacy and safety outcomes were not reported. Why not? I was also curious about the 15% of the population. Were they compared to the entire placebo group or a subset? I looked to Clinicaltrials.gov and came up empty handed. Not one to be daunted I discovered a few insights described by The Neurocritic.
As reported at AAIC 2016, in the full study population, neither intervention arm of the trial was different from placebo. However, in a prespecified analysis of a subgroup of the study population that was not taking an approved Alzheimer’s therapy at the beginning of the study (in other words, who received LMTM as a monotherapy), there was a statistically significant benefit on the cognitive and functional outcomes, and brain atrophy measured by MRI. --Alzheimer’s Association AAIC Press Office
Once the twitter-verse exploded it seems New Scientist decided a revised headline was in order...
So what did we learn? The details have been discussed eloquently at Forbes, The New York Times, and even Buzzfeed. We have noticed quite consistently how thin the proof has become for old beliefs and heuristics. Why are we unable to fail? Listen here to TED speakers discuss how Failure is an Option. If context is everything, I would encourage you to listen to a specific speaker--Casey Gerald: When Beliefs Fail Us, How Do We Move Forward. The title to the post is from his powerful commentary.
I hope you watched or listened to the video. A core message worth the 14 minutes--"We fail to question one brick because we are afraid it will shake our entire foundation"
I think its time we begin to doubt and to believe something new. The evidence is there--are you brave enough?
Thoughtful discussions about content development and outcomes analytics that apply the principles and frameworks of health policy and economics to persistent and perplexing health and health care problems...
I think its time we begin to doubt and to believe something new. The evidence is there--are you brave enough?
Thoughtful discussions about content development and outcomes analytics that apply the principles and frameworks of health policy and economics to persistent and perplexing health and health care problems...
