WEBVTT - Getting Answers on Vaccine Boosters 0:00:15.396 --> 0:00:24.236 Pushkin from Pushkin Industries. This is Deep Background, the show 0:00:24.276 --> 0:00:27.276 where we explore at the stories behind the stories in 0:00:27.276 --> 0:00:32.076 the news. I'm Noah Feldman. Regular listeners of this podcast 0:00:32.196 --> 0:00:35.196 know that we view one of our chief jobs as 0:00:35.356 --> 0:00:39.116 keeping you updated on the twists and turns of developments 0:00:39.156 --> 0:00:42.876 relating to COVID, in particular when we seem to be 0:00:42.956 --> 0:00:47.796 at a confusing or complex juncture point in the process. 0:00:48.436 --> 0:00:52.476 We are at one of those points now, particularly with 0:00:52.516 --> 0:00:56.756 respect to the question of boosters. Back in August, the 0:00:56.796 --> 0:01:00.196 Biden administration announced that by September twentieth they plan to 0:01:00.236 --> 0:01:02.516 be giving out boosters on a broad scale in the 0:01:02.596 --> 0:01:08.036 United States. Almost immediately, this announcement met with pushback from 0:01:08.156 --> 0:01:13.076 senior career scientists, and then from scientists outside the government, 0:01:13.396 --> 0:01:17.276 and then ultimately from the politically appointed leaders of Scientific 0:01:17.396 --> 0:01:21.076 Agencias events seem to come to a head in the 0:01:21.156 --> 0:01:24.996 last week or so, they were dueling articles in different 0:01:25.036 --> 0:01:27.956 medical journals, the Lancet out of the United Kingdom and 0:01:27.996 --> 0:01:31.476 the New England Journal of Medicine advising, roughly speaking, different 0:01:31.516 --> 0:01:35.556 approaches or paths on the booster question. Then an advisory 0:01:35.596 --> 0:01:40.916 committee of scientists and physicians to the FDA focusing on vaccines, 0:01:41.156 --> 0:01:44.716 had a public meeting last week to discuss these matters. Meanwhile, 0:01:44.876 --> 0:01:49.156 this week, a separate advisory committee, also of independent scientists 0:01:49.156 --> 0:01:53.476 and physicians, that advises the CDC is also expected to 0:01:53.516 --> 0:01:58.476 weigh in. The upshot is a lot of confusion, certainly 0:01:58.516 --> 0:02:01.276 for me, but I think also for many people who 0:02:01.396 --> 0:02:03.796 like me, have been trying to figure out what's going on. 0:02:04.556 --> 0:02:07.396 To help us walk through this confusion and give us 0:02:07.476 --> 0:02:11.716 some clear understanding the process and of the opinions, we're 0:02:11.716 --> 0:02:15.316 turning today to doctor Genevieve Cantor, who is a Research 0:02:15.356 --> 0:02:18.836 Assistant Professor at the Perilman School of Medicine at the 0:02:18.916 --> 0:02:22.836 University of Pennsylvania. Doctor Cantor is trained as an economist, 0:02:22.836 --> 0:02:26.396 which means her central expertise is on the modeling and 0:02:26.436 --> 0:02:32.236 the measuring of causation, precisely the issues at hand today. Furthermore, 0:02:32.356 --> 0:02:36.996 her substantive area of expertise includes regulatory policy and the 0:02:37.116 --> 0:02:44.516 regulation of biomedical technologies, including vaccines, and the relationship between industry, government, politicians, 0:02:44.516 --> 0:02:48.036 and regulators. In short, doctor Cantor is the perfect person 0:02:48.236 --> 0:02:52.116 with whom to get some clarity in these very complex waters. 0:02:52.556 --> 0:02:57.676 Doctor Cantor thank you so much for joining me. Let's 0:02:57.756 --> 0:03:02.796 start with the underlying fascinating challenge of the science here. 0:03:02.956 --> 0:03:06.556 Just in the last week, two studies in highly respected 0:03:06.796 --> 0:03:11.076 places with roughly speaking at least in Layman's terms, contradictory 0:03:11.116 --> 0:03:15.876 messages about boosters, with the Lancet article suggesting that it's 0:03:15.876 --> 0:03:19.476 too soon to recommend boosters for people other than the 0:03:19.516 --> 0:03:22.476 oldest and the most infirm, and then the new England 0:03:22.556 --> 0:03:26.436 Journal study relying on Israel data suggesting that boosters had 0:03:26.436 --> 0:03:29.796 a substantially helpful effect for the part of the population 0:03:29.796 --> 0:03:36.076 that was studied. There. What is a reasonable person to think, right, So, 0:03:36.516 --> 0:03:39.796 the way it would interpret these two new papers is 0:03:39.836 --> 0:03:45.076 that the Journal article reports on one particular case, which 0:03:45.156 --> 0:03:49.516 certainly compelling case in Israel, where Israel launched its third 0:03:49.676 --> 0:03:56.356 vaccination campaign involving boosters, and in that study they staggered 0:03:56.356 --> 0:04:01.676 their role out, initially targeting the sixty plus population, eventually 0:04:02.036 --> 0:04:07.796 reaching the younger population. They found that administering boosters to 0:04:08.436 --> 0:04:13.836 the oldest population did reduce infections as well as severe 0:04:14.316 --> 0:04:19.596 disease and hospitalizations. That's pretty compelling evidence. And although there 0:04:19.636 --> 0:04:22.156 are some critiques that can be made of that study, 0:04:22.156 --> 0:04:25.036 which I'm happy to go into in general. This was 0:04:25.036 --> 0:04:27.236 a study that was presented, as you may know, during 0:04:27.396 --> 0:04:31.556 last week's Friday's f Day Advisory Committee meeting, and on 0:04:31.556 --> 0:04:34.476 the whole, that committee found that study to be compelling. 0:04:34.916 --> 0:04:39.756 The Lancet paper, I would say it doesn't present new information, 0:04:39.796 --> 0:04:41.596 As you said, it's sort of a study of studies. 0:04:41.756 --> 0:04:44.756 I might actually even just say that it's more of 0:04:44.796 --> 0:04:48.396 a framework, a holistic framework how we might consider the 0:04:48.476 --> 0:04:52.276 various pieces of data that we're seeing to justify boosters. 0:04:52.476 --> 0:04:55.236 It addresses do we know whether there's a need at all, 0:04:55.556 --> 0:04:59.236 is it greater among certain populations? How can we interpret 0:04:59.396 --> 0:05:03.236 some of that observational data. It also talks about considerations 0:05:03.236 --> 0:05:07.396 in terms of what impact that booster shot would have 0:05:07.556 --> 0:05:10.996 on either severe disease and hospit realizations or on infections. 0:05:11.036 --> 0:05:13.916 Those are two very distinct and important things. So I 0:05:13.956 --> 0:05:17.316 would consider that less a summary of the existing knowledge, 0:05:17.396 --> 0:05:19.836 but more of here the considerations we need to take 0:05:19.876 --> 0:05:24.116 into account. And perhaps there are also some political purposes 0:05:24.156 --> 0:05:27.596 behind that article, which I'm happy to also get into. Well, 0:05:27.636 --> 0:05:29.956 we need to talk about the political purposes, but again 0:05:29.996 --> 0:05:31.876 I'm trying to the extent we can and it's always 0:05:31.916 --> 0:05:33.556 hard here, and that's one of the reasons this topic 0:05:33.636 --> 0:05:38.716 is so fascinating to differentiate the policy, the regulatory component, 0:05:38.836 --> 0:05:42.356 and the scientific component, and they're intertwined. In my reading 0:05:42.436 --> 0:05:45.116 of the Lancet it sounded to me as though they 0:05:45.156 --> 0:05:50.396 were making a pretty substantive policy point, namely, do not 0:05:50.716 --> 0:05:54.436 jump from the Israeli data, which they had seen preliminary 0:05:54.516 --> 0:05:59.116 versions of, to concluding that we should go out in 0:05:59.116 --> 0:06:03.156 the United States and approve boosters for a wide swath 0:06:03.396 --> 0:06:06.876 of the population, which the Biden administration had already done 0:06:07.276 --> 0:06:11.156 weeks ago, now saying by September twentieth they hoped to 0:06:11.156 --> 0:06:15.956 start approving boosters. And so that's a huge practical difference. 0:06:15.996 --> 0:06:19.676 And just another piece of detail there that seems salient 0:06:19.716 --> 0:06:23.756 to me is that the Lancet study also questioned the 0:06:23.876 --> 0:06:27.716 israel data, not the version that was published a couple 0:06:27.756 --> 0:06:30.636 of days later, but their preliminary version, by pointing to 0:06:30.716 --> 0:06:34.996 some potential methodological flaws in that Israel's study, not that 0:06:35.036 --> 0:06:36.796 they were flaws in the way the study was done, 0:06:36.836 --> 0:06:39.076 but just in the data that was available at the time, 0:06:39.396 --> 0:06:41.476 namely that it was a relatively short period of time 0:06:41.676 --> 0:06:44.476 that was being studied after vaccination, and the fact that 0:06:44.476 --> 0:06:47.876 they bothered to do that in the Lancet study sent 0:06:48.036 --> 0:06:51.716 to me the message that this is really about two 0:06:51.756 --> 0:06:56.756 approaches to boosters, one approach saying full steam ahead, the 0:06:56.796 --> 0:06:59.156 one that the Biden administration had originally taken and now 0:06:59.196 --> 0:07:02.796 seems to be backpedeling from, and the other the more 0:07:02.836 --> 0:07:06.876 cautious Let's wait and see. Let's not acclimate the public 0:07:06.916 --> 0:07:09.436 to thinking that it needs boosters all the time the 0:07:09.476 --> 0:07:13.756 public lose faith in the phenomenology, in the phenomenon of boosters, 0:07:14.556 --> 0:07:17.756 Let's be sure that the data really bear it out. 0:07:17.796 --> 0:07:19.996 And let's not forget that if we have extra doses 0:07:20.036 --> 0:07:22.356 for boosters, maybe we should be using those to send 0:07:22.356 --> 0:07:25.756 them all around the world rather than using them in 0:07:25.756 --> 0:07:28.796 the US on third doses. So I guess I want 0:07:28.796 --> 0:07:31.276 to ask, am I overreading this? I mean, is it 0:07:31.356 --> 0:07:34.236 unfair to say, as I am basically saying from a 0:07:34.316 --> 0:07:37.196 late person's perspective that it seems like they're two pretty 0:07:37.196 --> 0:07:40.916 opposed of viewpoints here. I might take the view that 0:07:40.956 --> 0:07:46.276 it is possible for those who want to push forward 0:07:46.996 --> 0:07:53.156 to see more evidence that might convince them otherwise. You know, 0:07:53.196 --> 0:07:55.516 one of the really surprising things that came out of 0:07:55.516 --> 0:07:59.276 that statement that was issued by those political appointees and 0:07:59.516 --> 0:08:04.636 including the Acting Commissioner of the FDA, CDC director, US 0:08:04.676 --> 0:08:08.956 Surgeon General and IH and so on, is that it's 0:08:08.956 --> 0:08:12.116 not clear that they had all the information that say, 0:08:12.516 --> 0:08:16.236 you know, the FDA Advisory Committee in its review process 0:08:16.396 --> 0:08:19.796 did and I guess I'm up the view that what 0:08:19.956 --> 0:08:24.236 the Lansward article was doing was trying to present additional 0:08:24.276 --> 0:08:28.716 information that might inform you, if you want to characterize it, Oh, 0:08:28.756 --> 0:08:31.916 here's an opposing view of full speed ahead, sort of saying, hey, 0:08:32.156 --> 0:08:35.076 here are some additional considerations you might not have thought about. 0:08:35.316 --> 0:08:37.636 I think one of the most interesting things that came 0:08:37.636 --> 0:08:40.276 out of the Advisory Committee on Friday, in case you 0:08:40.356 --> 0:08:42.796 didn't have the time to watch all eight hours of it, 0:08:42.836 --> 0:08:46.116 was to highlight that one of the pieces of evidence 0:08:46.196 --> 0:08:50.756 that Fiser presented as justifying the need for boosters, they 0:08:50.796 --> 0:08:54.436 had not made that data available to the FDA to review. 0:08:54.836 --> 0:08:57.436 This was one concern that was highlighted in the lanswerd article, 0:08:57.836 --> 0:09:00.956 and it is a concern that maybe those who made 0:09:00.956 --> 0:09:04.036 the political pointies that made the decision to have a 0:09:04.116 --> 0:09:06.116 plan to set a date and to go ahead with 0:09:06.156 --> 0:09:09.996 it may not have fully taken into account. That was 0:09:10.076 --> 0:09:12.196 very helpful. I think it would be helpful for me 0:09:12.436 --> 0:09:16.196 and possibly for listeners to march through for a moment 0:09:16.316 --> 0:09:19.156 all of the different actors who have been involved in this, 0:09:19.516 --> 0:09:22.396 because in preparation for our conversation, I made myself a 0:09:22.476 --> 0:09:25.116 little chart, and I was myself kind of mind blown 0:09:25.156 --> 0:09:27.236 by just how many actors are involved right now. So 0:09:27.316 --> 0:09:30.716 let's take a half step back. First of all, you've 0:09:30.756 --> 0:09:34.796 got the White House, which has the authority to say 0:09:34.796 --> 0:09:36.956 what it plans to do, but not in every case 0:09:36.996 --> 0:09:40.796 the full authority to order the FDA or the CDC 0:09:40.956 --> 0:09:43.796 to dirt and do certain things, because there's a complex 0:09:43.916 --> 0:09:47.956 regulatory procedure a law that they would have to follow. 0:09:47.996 --> 0:09:49.396 So when they say they're going to do something, what 0:09:49.436 --> 0:09:52.476 they mean is we hope this will happen, not we 0:09:52.556 --> 0:09:56.076 can order even our political appointees at the FDA to 0:09:56.436 --> 0:10:00.076 approve things. If it were otherwise than Donald Trump, you 0:10:00.516 --> 0:10:02.716 could have ordered and probably would have ordered, the FDA 0:10:02.716 --> 0:10:04.556 and the CDC to do all sorts of things independent 0:10:04.556 --> 0:10:07.636 of the science. So there's the White House. Then there's 0:10:07.636 --> 0:10:15.836 the f which is in charge of formal approvals of 0:10:16.596 --> 0:10:20.396 new vaccines or new uses for vaccines, and is also 0:10:20.676 --> 0:10:26.196 authorized to issue emergency use authorizations. Then there are career 0:10:26.276 --> 0:10:30.196 scientists as opposed to political appointees within the FDA and 0:10:30.236 --> 0:10:34.236 the Centers for Disease Control. And then last, but not least, 0:10:34.796 --> 0:10:39.716 there is an Advisory Committee on vaccines that advises the 0:10:39.756 --> 0:10:44.196 FDA that's made up of outside physicians and scientists. And 0:10:44.276 --> 0:10:46.356 in the last week it seems like all of these 0:10:46.396 --> 0:10:49.236 actors have been doing things right. There was this meeting 0:10:49.356 --> 0:10:52.196 of the FDA Advisory Committee that's the committee of outsiders. 0:10:52.396 --> 0:10:54.596 But then there was a public statement from a whole 0:10:54.636 --> 0:10:57.476 bunch of political appointees that itself seemed to push a 0:10:57.516 --> 0:11:00.796 little bit against the Biden administration. And then the Biden 0:11:00.836 --> 0:11:05.116 administration itself, through a spokesperson, said well, we were always 0:11:05.116 --> 0:11:07.036 planning to follow the science and we will continue to 0:11:07.036 --> 0:11:09.796 follow the science. But they, of course had been criticized 0:11:09.836 --> 0:11:12.716 for being out ahead of the science on these things. 0:11:13.436 --> 0:11:15.796 So I guess let me start by asking have I 0:11:15.916 --> 0:11:18.996 left out any important actors here? And since you study 0:11:19.076 --> 0:11:22.156 this process for a living, how do you think about 0:11:22.156 --> 0:11:25.636 the different actors here? And they're different roles because this 0:11:25.676 --> 0:11:28.356 is one of those instances where the distribution of political 0:11:28.396 --> 0:11:32.676 authority and regulatory authority has huge practical implications for us 0:11:32.676 --> 0:11:34.676 on a day to day basis. It's going to determine 0:11:35.036 --> 0:11:37.916 whether we're going to get shots in our arms or not, 0:11:38.076 --> 0:11:41.036 and who's going to get them, you know. To add 0:11:41.116 --> 0:11:43.636 more fun to the mix, I would actually add two 0:11:43.676 --> 0:11:47.756 other entities that are parallel to what you mentioned with 0:11:47.836 --> 0:11:51.796 the FDA, So the CDC because we're talking about infectious 0:11:51.836 --> 0:11:56.156 diseases and vaccines in particular, as well as its advisory committee, 0:11:56.396 --> 0:12:00.996 the ACIP, which is the Advisory Committee on Immunization Practices. 0:12:01.476 --> 0:12:05.316 So yes, so they're all interacting. I have the feeling 0:12:05.356 --> 0:12:08.156 in China, where they've vaccinated a billion people, they don't 0:12:08.196 --> 0:12:11.556 have six different is pushing against each other. That's right. 0:12:11.596 --> 0:12:14.836 They either don't or they do, but it's all behind 0:12:14.876 --> 0:12:17.356 the scenes, and then they issue a single statement that 0:12:17.476 --> 0:12:20.876 everyone nods and agrees. In this case, and I think 0:12:20.916 --> 0:12:23.756 it is an unusual case of the interaction between the 0:12:23.756 --> 0:12:27.676 FDA and the CDC because a of the particular condition 0:12:27.796 --> 0:12:32.076 which is infectious, and secondly because of vaccines being the 0:12:32.116 --> 0:12:35.236 issue here as opposed to therapeutics, where then FDA would 0:12:35.276 --> 0:12:38.836 have full authorization for the regulation. And actually one thing 0:12:38.836 --> 0:12:41.756 we've one entity we've also forgotten are the drug companies 0:12:42.076 --> 0:12:47.396 or the manufacturers themselves issuing these vaccines. So boy, in 0:12:47.516 --> 0:12:49.836 terms of summarizing how they all fit together, you know, 0:12:49.996 --> 0:12:53.276 we have a vaccine manufacturer, in this case Viser. They 0:12:53.316 --> 0:12:56.636 have a product of vaccine that's been approved and so 0:12:56.716 --> 0:13:00.756 they submitted that application to the FDA. The FDA can 0:13:00.836 --> 0:13:04.716 make a decision on that application, with or without the 0:13:04.756 --> 0:13:09.396 Advisory Committee consultation. In this case, they've chosen to do that, 0:13:09.756 --> 0:13:12.356 and in general that's considered a good thing. It's generally 0:13:12.356 --> 0:13:16.236 more transparent. Probably perceived it correctly as being less political 0:13:16.396 --> 0:13:21.156 because these are outside experts, they're independent, and they can 0:13:21.156 --> 0:13:24.116 give the recommendation to the FDA. So I would say 0:13:24.196 --> 0:13:26.676 that's one part of this process that's a little unusual 0:13:26.836 --> 0:13:31.916 as well. The FDA doesn't always send applications to the 0:13:31.956 --> 0:13:35.276 Advisory Committee. In fact, you know, our study which covered 0:13:35.316 --> 0:13:39.396 about twenty years of vaccine licensure history, showed that about 0:13:39.396 --> 0:13:42.396 the half of all new vaccine applications are actually sent 0:13:42.436 --> 0:13:45.196 to the Advisory Committee. But Steve Hahn, you know, when 0:13:45.196 --> 0:13:48.636 he was Commissioner, made a commitment to say everything involving 0:13:48.716 --> 0:13:51.556 COVID would go to the Advisory Committee. So that's been 0:13:51.596 --> 0:13:54.876 a big and i think helpful change. So what happened 0:13:54.956 --> 0:13:57.836 last week the Advisory Committee for the FDA men, they 0:13:57.836 --> 0:14:01.396 gave their recommendations, which I'm sure we'll go into. The 0:14:01.436 --> 0:14:04.236 FDA then has to make a decision based on the 0:14:04.276 --> 0:14:08.596 recommendations of the Advisory Committee. Most of the time seventy 0:14:08.596 --> 0:14:11.636 five percent of the time they do follow those recommendations, 0:14:11.636 --> 0:14:15.636 but sometimes significantly they do not. They issue that recommendation 0:14:16.036 --> 0:14:20.236 for the conditions under which the vaccine is able to 0:14:20.236 --> 0:14:24.876 be administered. Advisor can market that product. After that, the 0:14:25.116 --> 0:14:30.236 Advisor Committee to the CDC, which is ACIP, convenes, uses 0:14:30.276 --> 0:14:33.316 its own information, which includes what the FDA saw but 0:14:33.356 --> 0:14:37.236 also actually includes other types of data issues its recommendation, 0:14:38.036 --> 0:14:40.676 and then the CDC can decide to follow it or not. 0:14:41.036 --> 0:14:45.556 Whatever the decides is generally considered vaccine policy for this 0:14:45.636 --> 0:14:49.676 particular vaccine. After that, then the White House comes in 0:14:50.076 --> 0:14:53.036 and to the extent that they can execute a plan 0:14:53.156 --> 0:14:56.636 for distribution help the states to do so. That's where 0:14:56.636 --> 0:15:01.276 their authority lies. So the statement was highly highly unusual. 0:15:01.316 --> 0:15:03.876 They statement they issued in August about we have a 0:15:03.916 --> 0:15:06.076 plan and by the way, we're going to execute at 0:15:06.076 --> 0:15:10.676 September twentieth. Yes, the White statement, that's right, and we 0:15:10.756 --> 0:15:13.596 have a plan. We're going to execute it on September twentieth, 0:15:13.836 --> 0:15:16.876 before the FDA Advisory Committee has reviewed it, before the 0:15:16.956 --> 0:15:20.316 FDA it's made its decision, before the CDC Advisory Committee 0:15:20.356 --> 0:15:23.636 has reviewed it, before the CDC has made its recommendation. 0:15:24.236 --> 0:15:27.796 That's highly unusual. And yes, so that is an anomaly 0:15:28.116 --> 0:15:31.396 in the typical process. That was wildly helpful. I feel 0:15:31.396 --> 0:15:33.476 like I know a lot more than when I started. 0:15:33.676 --> 0:15:37.636 Before we turn to the advisory committee's opinion. I actually 0:15:37.716 --> 0:15:40.916 now have to pause to ask you, is this process 0:15:41.036 --> 0:15:43.516 a good process? I mean that is to say, it 0:15:43.596 --> 0:15:47.356 may be a great process under ordinary circumstances where time 0:15:47.436 --> 0:15:50.636 is not of the essence, where time is of the essence. 0:15:51.076 --> 0:15:55.996 Is this very elaborate, complex, multi step process really value 0:15:55.996 --> 0:15:59.156 adding or is it primarily just about protecting us from 0:15:59.156 --> 0:16:02.316 an administration whether Biden's or Trumps that just says this 0:16:02.356 --> 0:16:04.516 is what we're doing and here's how we're doing it, 0:16:04.836 --> 0:16:09.716 without listening to the scientists. I do believe that process 0:16:09.956 --> 0:16:15.796 is important and that this particular process, which respects external 0:16:16.556 --> 0:16:21.036 expert independent advice through the formal process of advisory committees 0:16:21.316 --> 0:16:28.476 is almost indispensable, especially under these circumstances where public trust 0:16:28.596 --> 0:16:31.516 is important. Can I just pause there for one second, Jenny, 0:16:31.596 --> 0:16:36.196 because I totally agree the contradictory messages, or let's call 0:16:36.236 --> 0:16:38.556 them to be more polite messages in tension with each other, 0:16:38.796 --> 0:16:41.516 even though, as I just explained, I think their contradictory 0:16:41.596 --> 0:16:44.556 I think those are undercutting public trust. I think if 0:16:44.596 --> 0:16:48.316 you want public trust, you want the leading regulatory authorities 0:16:48.316 --> 0:16:51.556 and the scientists to speak publicly to the extent possible 0:16:51.876 --> 0:16:55.916 with one voice. It takes a very sophisticated public to say, well, 0:16:56.036 --> 0:17:01.436 there's real disagreement among epidemiologists and statisticians and scientists, and 0:17:01.476 --> 0:17:04.476 therefore I really trust this process because they're disagreeing with 0:17:04.476 --> 0:17:07.276 each other writing the public eye. I mean hard to 0:17:07.316 --> 0:17:10.316 imagine that in real life, very many actual people have 0:17:10.596 --> 0:17:14.756 such a worldly, sophisticated conception of the value of this 0:17:14.796 --> 0:17:21.436 kind of disagreement. So the alternative that you're proposing is, well, 0:17:21.516 --> 0:17:25.316 do it behind closed doors, you know, have the input, 0:17:25.596 --> 0:17:28.436 have a more streamlined process, or at least under emergency 0:17:28.436 --> 0:17:31.236 conditions have a more streamline process, so that what the 0:17:31.276 --> 0:17:35.276 public hears is the US government is recommending boosters, or 0:17:35.316 --> 0:17:38.956 the US government is not recommending boosters. I'm not recommending that. 0:17:38.996 --> 0:17:41.996 I'm raising that as an alternative. And you yourself mentioned that, 0:17:42.036 --> 0:17:44.556 you know, in the Chinese system, there of course is 0:17:44.596 --> 0:17:48.676 internal disagreement, but it's mostly behind closed doors. But then 0:17:48.676 --> 0:17:52.796 the government does speak with a single voice. It is 0:17:52.836 --> 0:17:56.076 interesting that you're saying that this chaotic process, the way 0:17:56.076 --> 0:17:59.116 it's played out in the public, at least in recent times, 0:17:59.116 --> 0:18:04.156 has ledged you or conjecture that public trust is diminishing. 0:18:04.596 --> 0:18:07.596 You know. My read of the issue is that really 0:18:07.636 --> 0:18:12.516 the tension is between the White House and it's political 0:18:12.636 --> 0:18:18.716 or partisan motives versus the scientists FDA, CDC, and IH 0:18:18.756 --> 0:18:22.476 and so on. And so I read the Lancet article 0:18:22.916 --> 0:18:26.756 as saying, especially since it was written by two career 0:18:26.836 --> 0:18:32.316 scientists who are resigning, as sort of a signal saying, 0:18:32.476 --> 0:18:36.556 you know, we had thought that this political risk that 0:18:36.596 --> 0:18:40.276 we experienced in the previous administration was over, and perhaps 0:18:40.276 --> 0:18:43.436 in its extreme form it is. But you know, there 0:18:43.436 --> 0:18:47.636 are also political risks here, and we'd like to raise 0:18:47.756 --> 0:18:50.276 this issue and also set out a framework for what 0:18:50.316 --> 0:18:54.436 we think should be driving the scientific decision as opposed 0:18:54.436 --> 0:18:59.916 to whatever is driving the White House action. We'll be 0:19:00.036 --> 0:19:12.716 right back. So now you've offered a kind of master 0:19:12.836 --> 0:19:16.036 interpretation of what's going on here for me and for listeners. 0:19:16.236 --> 0:19:18.276 So let me say it back to you, and to 0:19:18.316 --> 0:19:20.916 make sure that I'm hearing what you're saying correctly. What 0:19:20.956 --> 0:19:24.116 I think I hear you saying is actually, although there 0:19:24.156 --> 0:19:26.636 are lots of different actors here, what really matters is 0:19:26.676 --> 0:19:30.436 there two voices. There's the White House, which is elected 0:19:30.436 --> 0:19:32.996 politicians and the people who work for them, who said 0:19:33.036 --> 0:19:35.876 in August we're gonna get boosters out there on September twentieth, 0:19:35.876 --> 0:19:38.596 because we've heard some early reports from Israel that seemed 0:19:38.596 --> 0:19:40.396 like boosters are a good idea, so we're doing it. 0:19:40.396 --> 0:19:44.956 They wanted to get out ahead of it, and then fairly, unifically, 0:19:45.076 --> 0:19:49.836 fairly with one voice, the senior scientists within the government 0:19:50.636 --> 0:19:53.756 and the senior scientists outside the government who advised the 0:19:53.796 --> 0:19:59.476 government are saying in response, WHOA not the right move, 0:20:00.196 --> 0:20:02.436 don't do it right away, Maybe only do it for 0:20:02.476 --> 0:20:05.716 the oldest and potentially sickest people. We're going to have 0:20:05.756 --> 0:20:10.116 to follow a process here, and that's way these things 0:20:10.196 --> 0:20:13.036 should be done. And as you're adding, we thought we 0:20:13.076 --> 0:20:14.316 had to deal with this kind of thing from the 0:20:14.316 --> 0:20:16.436 Trump people, We never imagine we'd have to deal with 0:20:16.476 --> 0:20:20.116 it from the Biden people. And in that context, this 0:20:20.196 --> 0:20:22.236 Lancet article, which as you point out, was written by 0:20:22.276 --> 0:20:25.756 two senior career scientists who announced just before the article 0:20:25.796 --> 0:20:27.676 came out that they would be quote unquote retiring, which 0:20:27.716 --> 0:20:31.916 effectively means resigning, was a kind of way of saying 0:20:31.916 --> 0:20:34.076 to the White House, we can't work with you, guys. 0:20:34.716 --> 0:20:36.476 You know we're gonna We're willing to go down with 0:20:36.516 --> 0:20:39.236 the ship in order to stand up for the processes 0:20:39.236 --> 0:20:41.276 of science. And if that's the interpretation that you're saying, 0:20:42.196 --> 0:20:46.356 that's very clarifying. It's also reassuring. It basically suggests that 0:20:46.396 --> 0:20:47.956 is to say, at least, it's reassuring if you trust 0:20:47.956 --> 0:20:51.916 the scientists, that the scientists are saying, slow down, and 0:20:52.356 --> 0:20:54.276 they will probably win. I mean, we can talk about 0:20:54.276 --> 0:20:55.636 that in a moment too, but it seems like they 0:20:55.676 --> 0:21:01.316 will probably win. Since the public statement by the advisory 0:21:01.356 --> 0:21:05.196 body to the FDA did seem very much to be 0:21:05.276 --> 0:21:09.436 in line with the Lancet article written by among there's 0:21:09.956 --> 0:21:14.676 these two senior career scientists. It is my hope that 0:21:14.716 --> 0:21:18.556 the scientific process will work itself out. And it's even 0:21:18.636 --> 0:21:23.036 more compelling that these external career scientists, Marin Gruber and 0:21:23.276 --> 0:21:26.476 Phil Krause were at the FDA meeting, the Advisor Committee 0:21:26.476 --> 0:21:29.316 Meeting's what they said to tell us what they said. Sure, 0:21:29.716 --> 0:21:34.516 there are two aspects of the booster decision. One is 0:21:34.556 --> 0:21:40.356 to establish the claim that the protection from the initial 0:21:40.436 --> 0:21:45.876 series of two doses is diminishing, and the second is 0:21:46.076 --> 0:21:49.876 a booster shot of the same dose, the same vaccine 0:21:50.436 --> 0:21:55.676 six months later will be effective in increasing protection. So 0:21:55.836 --> 0:21:59.556 there are issues actually with both of those claims, and 0:21:59.636 --> 0:22:02.996 so that's why the Advisor Committee sort of, if you like, 0:22:03.036 --> 0:22:06.196 split the baby the way they did so. In terms 0:22:06.236 --> 0:22:08.996 of establishing the need for boosters, you would think this 0:22:09.156 --> 0:22:12.556 would be pretty straightforward, you know, the measures that we 0:22:12.596 --> 0:22:16.196 are most interested in, is the protection from severe disease 0:22:16.196 --> 0:22:20.516 and hospitalization and death diminishing over time, and is it 0:22:20.716 --> 0:22:24.996 losing its ability to protect against infection and to establish 0:22:25.076 --> 0:22:29.516 the need both basically, what we've what Feiser has appealed to, 0:22:29.796 --> 0:22:33.876 in general, what people supporting boosters have appealed to, are 0:22:33.876 --> 0:22:39.236 these observational studies that have tracked people who got the 0:22:39.316 --> 0:22:42.956 vaccine and compared them to people who didn't, and have 0:22:43.076 --> 0:22:47.196 we seen over time and increase in hospitalizations and severe disease, 0:22:47.436 --> 0:22:51.676 increase in infections. Now, as it happens, we did, you 0:22:51.676 --> 0:22:53.756 would think that, you know, you can do a straightforward inference, 0:22:54.116 --> 0:22:57.556 but it turns out there comes some complicating factors. The 0:22:57.596 --> 0:23:01.196 two big complicating factors are one, at the same time 0:23:01.236 --> 0:23:04.996 that you're seeing increase in hospitalizations in cases, you're also 0:23:05.036 --> 0:23:08.516 seeing the emergence of the delta variant. So you know, 0:23:08.556 --> 0:23:11.236 are we seeing these increase in hospitalizations because of the 0:23:11.276 --> 0:23:14.396 delta variant where the vaccine may not be as effective, 0:23:14.756 --> 0:23:18.476 or because the protection conferred by the vaccine is waning? 0:23:18.876 --> 0:23:21.556 But connection about So this is the part really, I 0:23:21.596 --> 0:23:23.596 think where you're getting to now, where the rubber really 0:23:23.636 --> 0:23:28.156 meets the road. There is this data that suggests inferentially 0:23:28.476 --> 0:23:35.356 that even against delta, you get reduced hospitalizations and reduced 0:23:35.596 --> 0:23:39.316 severity of illness, at least in the older population by 0:23:39.476 --> 0:23:42.916 adding the booster. So even though I hear you when 0:23:42.916 --> 0:23:45.596 you say that it might be delta that's doing it, 0:23:46.116 --> 0:23:48.756 I would have thought that it wouldn't and that sounds plausible. 0:23:48.836 --> 0:23:51.196 I would have thought that that wouldn't matter if we 0:23:51.316 --> 0:23:55.436 know that even under conditions of delta we get some reduction. 0:23:55.516 --> 0:23:59.436 So what's wrong with that straightforward inference? Why is it 0:23:59.516 --> 0:24:03.196 such an implausible inference to say, look, we've got this. 0:24:03.316 --> 0:24:06.916 It's only one study, but it's a relatively powerful study 0:24:06.916 --> 0:24:10.236 with highly statistically significant results. And if we know from 0:24:10.236 --> 0:24:14.156 that study that there were substantial reductions and hospitalization and 0:24:14.196 --> 0:24:18.356 severe illness in that older population, why wouldn't we just 0:24:18.436 --> 0:24:22.036 make the inference even knowing that the inference isn't absolutely 0:24:22.076 --> 0:24:24.916 perfect and that there could be some confounding elements and 0:24:24.996 --> 0:24:28.236 that delta may play a role. Why does that matter? 0:24:29.156 --> 0:24:33.196 If the efficacy seems to be improved even against delta, 0:24:34.476 --> 0:24:38.076 this is a great, great point we can make that inference. 0:24:38.516 --> 0:24:41.796 And the question is for whom can we make that inference? 0:24:42.636 --> 0:24:47.076 Is it for the older population where the evidence seems strongest. 0:24:47.236 --> 0:24:49.676 There does seem to be a lot of evidence for 0:24:49.716 --> 0:24:53.396 the older population seventy five plus sixty plus that it 0:24:53.516 --> 0:24:59.196 is protective against both non delta and delta variants. There 0:24:59.236 --> 0:25:04.876 are two additional factors here. One is, if we want 0:25:04.916 --> 0:25:08.516 to extend it to the sixteen to sixty five. They're 0:25:08.596 --> 0:25:13.996 the evidence is less clear in terms of the actual effect. 0:25:14.436 --> 0:25:16.436 The second thing, and this is where we get into 0:25:16.676 --> 0:25:21.476 the scientific weeds on this is when you get a vaccine, 0:25:21.996 --> 0:25:26.636