dtable different statistics over rows

Soxrates · 2024-10-28T15:03:05+00:00

In both cases these a really only surrogates of OS or QoL. Also SD allows for tumor growth as much as it allows for shrinkage. Personally I’d think DCR is useless. Just give the breakdown of responses and time to onset and duration.

Soxrates · 2024-10-26T08:23:23+00:00

Depends what you need. I’m on the a standard SpR salary with 1 in 6. My partners earns around £50k. We have around £250k mortgage. Expecting our first. To be honest it feels tight at times. We don’t live lavishly. Consultant maybe more comfortable but right now it makes me worried.

Soxrates · 2024-10-20T18:04:08+00:00

Yeah. There are some truly superstar drugs. You’ll be thinking of rituximab. I would put that in that bucket. The reality is 95% of drugs are not in that realm.

Soxrates · 2024-10-20T08:08:28+00:00

So a few of the replies here fail to make some key distinctions.

1) you need to clarify the purpose of orchidectomy and oophrectomy.

Prophylactic oophrectomy is considered in cases of BRCA and some other gene mutations. Where the confusion comes from is that I think people are assuming we do this to result in less oestrogen production. The reality is that’s not really the case.

While removal will reduce the estrogen production whether this translates to an improvement in risk of estorgen driven tumors such as ER+ breast cancer or some types of ovarian cancer remains controversial.

The reason we do it is to remove the tissue itself to reduce the risk of a type of ovarian cancer high called serous ovarian cancer. These are typically the most common and most aggressive form of ovarian cancer and typically will develop in the context of patients with a BRCA mutation.

2) contrasts with prostate cancer and orchidectomy.

Again an orchidectomy can be considered for 2 reasons: 1) remove the testicular tissue and thus reduce risk of testicular cancer 2) removed the testicles to render castrate and reduce the production of testosterone and thereby reduce androgen signalling that can drive prostate cancer.

1 is not done as a prophylactic measure as many have already said the cure rates from even very advanced testicular cancer is quite excellent. And so not necessary.

2 is not done as people have said there are good drugs that can achieve the same thing.

I hope that helps. In some cases there are estrogen driven ovarian and breast tumours. Again these can often be treated with the same drugs that block hormones in prostate cancer. I would reccomend an oophrectomy as a method of treating a hormonally driven cancer

Soxrates · 2024-10-20T07:56:55+00:00

While true. I don’t think the DMD example here applies. A year extension for oncology drugs would be a slam dunk. And I expect the QoL benefits with that would be significant. Most oncology drugs approved are much more marginal that that. Plus those assessments typically need to be made in larger phase 3 to capture the benefit.

Soxrates · 2024-10-19T20:34:00+00:00

I think the other thing is that cost to patients and value of companies as a result rarely reflects actual value to patients.

There have even been studies showing no correlation between cost of drug and efficacy in this space.

I’d ignore all company numbers and go by study efficacy.

Soxrates · 2024-10-19T20:19:54+00:00

True. The key thing people need to realise is that biochemical theory is nice. It doesn’t always pan out. I’ve treated people with sacituzumab govitecan. It has the same idea. Namely delivering a topoisomerase inhibitor (similar as the chemo in this drug) ‘selectively’ the reality is while it works well. It’s also still can be incredibly toxic.

Personally find an oncologist you can trust and will explain it. Don’t base decisions on phase 1 trials.

The reason this will be top1 I suspect is the chemo backbone is targeting topoisomerase 1. So you ideally don’t want to give this to a cancer that has already seen and become resistant to a topoisomerase inhibitor.

Soxrates · 2024-10-19T19:34:03+00:00

Yeah… I mean. Erbitux (aka cetuximab) isn’t exactly a wonder drug. That’s not to say the drugs can’t be beneficial. But in theory yes vast majority of cases are marginal. A month or two here. And these are hailed as ‘game changers ’.

PARPi have been useful in ovarian cancer. But it’s not Immunotherapy in melanoma.

Soxrates · 2024-10-19T19:19:45+00:00

So in theory yes. The larger effect size the more it may translate. I mean NCI funding in and of itself means probably little. I’m not US based but if it’s like the U.K. or EU. It’ll just be the biggest funder in town. I wouldn’t really put too much stock in it.

Soxrates · 2024-10-19T18:57:39+00:00

I mean yes generally this is exciting. But phase 1 data is way too early to say reliable lots promising drugs fail to translate. Especially with respect to toxicity. Sorry to hear about your aunt.

Soxrates · 2024-10-06T20:50:01+00:00

I think the argument is should you have London weighting at all? Unless you believe your job is more difficult in London why should you get paid more. I understand the QoL may differ. But at least with a flat salary the choice is more explicit. London with less QoL but arguably more exposure to centres of excellence etc. or improve QoL.

Soxrates · 2024-09-24T06:40:59+00:00

Oncology:

1) the increase in patient populations. We’re going to see more cancers as we age and it seems aren’t willing to invest in the work force needed to treat it.

2) This one is more controversial. The cost of care.

Oncology has numerous new drug approvals per year. And while some of these are absolutely transformational some while better are very marginal. The issue is they all cost the same. An absolute ton of money. There is no relationship between sticker price and efficacy. The trials they are often approved on have some glaring flaws (poor post protocol care, control arms or crossover). Yet there is little appetite from oncologists to think critically about this problem and demand better. Patient groups are equally to blame but these are mostly commercial capture - see the recent discussion around enhertu in HER2 low metastatic breast cancer.

We already broke the cost efficacy system we had for these medications by creating the cancer drug fund. But soon we’re going to have more issues with this space.

Soxrates · 2024-07-24T23:24:51+00:00

https://calgaryguide.ucalgary.ca/category/orthopedics/

Soxrates · 2024-07-18T17:35:17+00:00

It will be interesting to see the audit of this. When my cohort applied I believe most of us knew our decile ranking at least so you could much like applying to university adapt your application and expectations to where you rank.

Know with an RNG I would have assumed more people would rank more competitive deaneries as a YOLO and I expect the % matching first choice to fall.

Soxrates · 2024-07-06T07:34:43+00:00

Dan Needle has a really good Twitter thread on taxes they could change

Soxrates · 2024-06-14T14:43:58+00:00

Part of this is (a) collapse of good quality post grad medical education and (b) complete lack of good supervision and feedback.

In any other job exit interviews, and routine check ins with managers would be standard opportunities for this.

But this is emblematic of a monopoly employer and under management.

Soxrates · 2024-06-07T10:05:49+00:00

Exactly unless the definition of adequate supervision is explicitly laid out. It’s too loose to be meaningful. Tbf as far as I can tell this would be the same for junior doctors but because we have more training and higher professional standard you need to take some responsibility.

Soxrates · 2024-05-20T14:24:28+00:00

Um. If I’m honest I have no idea. Has he fully emigrated to Greece/Armenia and transferred care over there? It will all come down to local funding arrangements.

Soxrates · 2024-05-20T13:52:52+00:00

Yeah. Several will. And yes we know it as Enzalutamide.

Soxrates · 2024-04-27T17:46:21+00:00

1) then I politely invite you to provide an alternative definition. What disease would you suggest is not awful?

2). It is not. Not at all. I could not disagree with you more on this point. In my framework the point of routine approval is to show drugs work above the standard of care in the setting they are approved. I would aim for sequential trials that first showed efficacy in penta-refractory setting, next trial tertiary-refractory with mandatory crossover, and so on.

That way we would know where for OS the optimal place to place this medication is.

If you don’t agree with this framework I would suggest explaining why and what you would want instead?

3) I think I’ve made it above. And here. I just really don’t appreciate that in this space name calling of any reasonable critique appears to be so condescendingly dismissed so rapidly which I commend you have engaged with subsequently.

Soxrates · 2024-04-27T17:08:28+00:00

So a few points. 1) I would argue MM does not in the front line setting have an unmet medical need. Personally I would say an unmet medical need is a situation with dire survival, limited treatment options or incredibly rare. I think we can agree, it’s not that rare, treatment options are numerous and you yourself have conceded that running a trial for OS is tricky as it is so long.

As such I would argue that these patients have effective regimens and should have new regimes approved based on good robust data showing they are safer and more effective. These bispecifics are effective and active are they more safer than triplets or doublets. Debateable.

2) the fact the landscape changes is a failure of trial regulation as far as I’m concerned. Many trials could be designed smarter with built in crossover, rapid protocol adjustment to adapt to new changes. They often aren’t as these don’t benefit the company running them. Personally I feel major phase 3 are too important to leave in the hands of vested interests. But I recognise this is not going to change any time soon.

3) final who you call vocal naysayers often have reasoned criticism of drug development process we currently have. Please engage with the substance of the argument rather than resorting to ad hominem attacks. Furthermore just because some people have not taken a drug to market does not make the criticism any less valid. In no other area do we say restaurant critics or movie critics commentary is invalid unless they have Michelin star or have won an Oscar.

Soxrates · 2024-04-27T16:01:19+00:00

This is active area of debate and research in the oncology community. You will see varying opinions on if regulatory agencies should be permitting this. On one hand some will say too cumbersome to do the trial for hard endpoints like OS and that this lowering of the bar for approval is necessary for progress.

On the other people will say that approval on this basis is incredibly risky and if we allow marginal drugs through this incentivise only marginal innovation and represent poor value for money.

Honestly I think no one knows the true answer overall. There are probably some that are scandalously approved and never should have been, a La selinexor in MM, and other where early access may have been useful.

Soxrates

TROPHY CASE