My paper with @anetrid and terrific colleagues @NIHBioethics @NINDSnews is out!. Ethical challenges for a new generation of early-phase pediatric gene therapy trials:. /1

RT @oziadias: Is this patient having a heart attack? . After 10+ years in the ER, it’s still an agonizing question for me. I turned the ang….

RT @KayteSB: In this new paper, we took a deep dive into how to equitably provide patients with opportunities to participate in clinical tr….

RT @leah_pierson: I argue here that the NIH's research agenda should better reflect public health needs. To accomplish this, the NIH shoul….

tl;dr - Interested to know the science behind '3rd shot in the primary series,' but don't let this framing obscure real ethical trade-offs in how we allocate vaccines. Getting the latter right seems more important. /end.

Re: ethics - Whatever we call 3rd doses, we should evaluate benefits/risks of using them in different ways & choose the best option. Eg, if you think new vax supply should be used as *1st* doses abroad, calling boosters '3rd shot in the primary series' should not change this. /2.

I'm curious whether this distinction is scientifically relevant, and struggling to see how it is ethically relevant. Re: science - What criteria make a vaccine dose 'part of the primary series'? How do we know that these criteria apply to 3rd dose, but not 4th or 5th doses? /1.

Please feel free to DM me for a PDF!. Extremely grateful to @anetrid, #SaskiaHendriks, and #ChristineGrady for two years of tireless mentorship. And to all of our @NINDSnews colleagues for their collaboration, insights, and inspiring approach to clinical research. /end.

-How should investigators engage with highly invested patient communities?. -How should investigators navigate disagreements with patient communities that are engaged in a trial?. /9.

-Should trials target patients with earlier- or later-stage disease?. -How should participants be selected fairly when not all eligible patients can be enrolled?. /8.

Together, we identify & analyze 6 key challenges for a new generation of early-phase pediatric GT trials:. -When is there enough preclinical evidence to begin clinical trials?. -How should risks and potential benefits be balanced in dose selection?. /7.

We wanted our approach to these trials to reflect their scientific, clinical, & ethical complexity. So, we teamed up with an inspiring team of clinical researchers & basic scientists conducting a GT trial for giant axonal neuropathy, an ultra-rare neurodegenerative disease. /6.

. they currently make trial participants ineligible for future (potentially more therapeutic) doses of any GT involving the same vector. Essentially, pediatric GT trials occupy the intersection of GT research ethics and pediatric research ethics. /5.

We identify a mix of factors:. -kids w/ serious conditions & limited options. -high uncertainty about GT harms & benefits. -patient communities highly motivated to shape and/or fund research. -GT-specific features. For example, some GTs are 'one-shot' deals, meaning. /4

Many GTs target rare diseases that affect children. So, clinical trials for these GTs need to enroll pediatric patients. What makes this ethically challenging?. /3.

#GeneTherapy—proposed in 1972 (!)—is "the introduction, removal, or change in the content of a person’s genetic code with the goal of treating or curing disease.". Now, the field is seeing breakthroughs. Since 2017, @US_FDA has approved first 5 GTs. Over 900 others in devel. /2.

RT @schuklenk: ‘We are witnessing a crime against humanity’: Arundhati Roy on India’s Covid catastrophe

The Good Fit — Why Medical Applicants’ Personal Statements Are Anything but Personal | NEJM

RT @WillSchupmann: Check out my editorial on why schools should play a part in disseminating the COVID-19 vaccine.

This editorial applies existing work on international research ethics to the case of multinational COVID-19 vaccine trials. Grateful to have these shoulders to stand on. Many thanks to the researchers & regulators (acknowledged in article) who helped us think this through. /end.