Reverse engineered: Trial of a new HIV drug

Clinical Brief – October 13th

The Brief

Darunavir/cobicistat (Prezcobix or Rezolsta) is a combination therapy for HIV that’s taken with two other drugs as part of a complete treatment regimen.

A recent company-sponsored trial reported that a new 4-drug-combo therapy with darunavir + cobicistat + emtricitabine + tenofovir alafenamide mashed into 1 pill is no worse than older boosted protease-inhibitor combination therapies.

In translation: D/C/F/TAF (the acronym for the 4-drug combo) in 1 pill is no worse than taking the same type of drugs individually.

The upshot? If we can read the data backward, it may mean that the older regimen is no worse than the new D/C/F/TAF. Older = eventual genericization = lowered cost with no loss of efficacy. Win?


The trend in HIV drug development

HIV meds have seen some pretty amazing advancements in the last few decades. Trouble is, trials over the last few years that led to the approval of new drugs have nearly all been non-inferiority trials (some examples off the top of my head: Atripla, Complera, Genvoya, Stribild, Triumeq).

Non-inferiority trials are easier than equivalence trials and less risky than superiority trials to run, but they don’t tell us much more than the fact that a new drug is no worse than an existing one.

So basically, these trials are saying that there’s a new pill, it might not do much more to treat HIV than what we already have, but at least it won’t cause unacceptable harm and it might be easier to take.


The D/C/F/TAF trial

In this trial, researchers recruited over 1,100 patients from 106 hospitals across North American and Europe. Everyone was virally suppressed on a boosted protease-inhibitor regimen.

Patients were then randomized 2:1 to switch to the new D/C/F/TAF or stay on their original regimen. The researchers assumed a non-inferiority margin of 4%.

Basically, it’s ok if more patients on D/C/F/TAF loses control of their HIV viral load, as long as it’s not more than 4% higher than those taking the older regimen, error bars and all, for the trial to conclude that D/C/F/TAF isn’t worse than the older regimen.

After nearly a year of treatment, only 2.5% of patients on D/C/F/TAF lost control of their HIV viral load vs 2.1% on the older pills. The difference between the two treatments worked out to be 0.4%, with an error bar spanning -1.5 to 2.2, which meant that D/C/F/TAF was no worse than the older pills.


Let’s have a bit of fun with their data

Open-ended logic question: If A is not better and not worse than B, does that mean B is also not better and not worse than A?

Statistically speaking, if we take their data and flip it upside down, we get the comparison between the older protease-inhibitor regimen vs D/C/F/TAF instead.

In this scenario, the treatment difference between the old pills vs D/C/F/TAF would be negative 0.4% with error bars hitting -2.2 to 1.5; which would then mean that the older protease-inhibitor regimen is no worse than D/C/F/TAF.


Bottom line

This subtle difference is important because when a company claims that a new, simpler treatment is no worse than the tried-and-true combination regimen of the same class, we could very well come up with this as a counterbalance:

The tried-and-true combination, once genericized, will likely cost considerably less, and may possibly be no worse than the shiny new pill.

What kind of cost savings is considerable? If I take a conservative approach and estimate that the generic would cost 25% less than a new pill that may cost about $2,500 USD a month, it could mean savings of $7,500 USD a year.

For an American with an average income of about $35k USD, this is 1/5th their annual salary. How much quality life would that buy?

*Full disclaimer, the study authors did not suggest that reversing their statistics is advised. These calculations are my personal ruminations only and have not been subject to peer-review.


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Post-op pain management for kids: Hold the morphine

Clinical Brief – October, 12th

The Brief

To manage pain after a kid gets surgery for something like implant removal or joint repair, would you pick morphine or a non-prescription painkiller?

A Canadian trial reported that over-the-counter painkillers may manage pain after an orthopedic surgery just as well as morphine, but comes with fewer side effects. Continue reading “Post-op pain management for kids: Hold the morphine”

Underreported: Law-enforcement-related deaths in America

Clinical Brief – October, 11th

The Brief

Yesterday, a study published in PLoS Medicine reported that a federal US government database designed to track law-enforcement-related deaths may be missing more than half of all deaths involving law enforcement.

In contrast, a nongovernmental database that scans media reports was found to have documented over 90% of deaths involving law enforcement.

Other worrying trends identified by the study’s researchers included underreporting when law-enforcement-related deaths are not caused by gunfire and underreporting in low-income counties. Continue reading “Underreported: Law-enforcement-related deaths in America”

What happens when lymph overflows

Clinical Brief – October 10th

The Brief

Limb lymphoedema is when lymph flows into the tissue after the nodes are surgically removed. It’s a fairly common procedure for the treatment of advanced-stage cancer including melanoma.

As a surgical complication, lymphoedema isn’t exactly a good thing to have. A recent study went further and detailed its negative psychological and physical impacts on patients with melanoma.

Researchers hope these results would help raise awareness of this complication and to improve its prevention and treatment. Continue reading “What happens when lymph overflows”

Notes on ESMO17: Breast cancer

Clinical Brief – October 9th

ESMO, or the European Society of Medical Oncology Congress, is an annual gathering of cancer experts and patient advocates. This is the last bit of my notes on some of the studies presented at this year’s ESMO that may be of use.


Adding a targeted therapy to endocrine therapy for HR+ breast cancer can increase the risk of side effects. But some targeted therapies may pose greater risks than others.

Researchers from the Institut Jules Bordet, Belgium, led a meta-analysis of trials to profile the comparative risks between classes of add-on targeted therapies. Continue reading “Notes on ESMO17: Breast cancer”

Notes on ESMO17: Supportive care

Clinical Brief – October 2nd

ESMO, or the European Society of Medical Oncology Congress, is an annual gathering of cancer experts and patient advocates. Here are some studies from this year’s ESMO that may be of use.


Drug interactions range from those that are harmless, to ones that pose serious risks that could put someone in a hospital. So, does a given cancer med have potentially worrisome drug interactions?

Look it up on Cancer-Druginteractions.org. Continue reading “Notes on ESMO17: Supportive care”

Notes on ESMO17: Tumors of the brain and spinal cord

Clinical Brief – September 29th

ESMO, or the European Society of Medical Oncology Congress, is an annual gathering of cancer experts and patient advocates. Here are some studies from this year’s ESMO that may be of use.


Glioblastoma multiforme is an aggressive type of brain cancer. Lowering the dose of bevacizumab (Avastin) for progressive glioblastoma multiforme may not have a detrimental impact on overall survival.

Researchers from Ireland reviewed the records of patients in their prospective national neuro-oncology center database. Nearly 120 patients were Continue reading “Notes on ESMO17: Tumors of the brain and spinal cord”

Notes on ESMO17: Psycho-oncology

Clinical Brief – September, 28th

ESMO, or the European Society of Medical Oncology Congress, is an annual gathering of cancer experts and patient advocates. Here are some studies from this year’s ESMO that may be of use.


Physicians and patients might have different takes on side effects when it comes to cancer treatments, says a study led by researchers at the Karolinska Institute, Sweden.

The study looked at data collected from a randomized Phase III trial comparing different chemo regimens in women with high-risk breast cancer. Continue reading “Notes on ESMO17: Psycho-oncology”

Notes on ESMO17: Cancer immunotherapy

Clinical Brief – September 27th

ESMO, or the European Society of Medical Oncology Congress, is an annual gathering of cancer experts and patient advocates. Here are some studies from this year’s ESMO that may be of use.


Final results of a Phase III trial confirm survival benefits of adjuvant chemo + cell-based immunotherapy for non-small-cell lung cancer.

Between 2007 and 2012, researchers from the Chiba Cancer Center, Japan, led an independent study Continue reading “Notes on ESMO17: Cancer immunotherapy”

Notes on ESMO17: Public health on cancer

Clinical Brief – September 26th

ESMO, or the European Society of Medical Oncology Congress, is an annual gathering of cancer experts and patient advocates. Here are some studies from this year’s ESMO that may be of use.


Researchers from the EU and Canada found that “in patients with advanced solid tumors, fewer than half of randomized controlled trials supporting FDA approval meet the threshold for clinically meaningful benefit using the ESMO-designed scale.

Researchers found 109 randomized controlled trials from the FDA’s database, which supported the approval of 63 drugs for Continue reading “Notes on ESMO17: Public health on cancer”