Goals of research

There has been an outpouring of dollars in basic molecular research. Many clinicians have joined in with their labs to push for “clinically relevant research”. It is evident that there would be a lot of duplication and overlap between it.

For example, look at IDH gene in the pathogenesis of gliomas. We know it carries a prognostic significance. We also know about the molecular pathogenesis. How does duplicating the research across different labs helps us or makes us any wiser?

The answer lies in the pharmaceutical business goldmine. Loath to spend on basic research in molecular pathways, the research, instead has been farmed out to a network of labs. It is easy for anyone to form a company and then sell out by being acquired. It is excellent for research ecosystem as it brings about new innovative ideas, but there are some serious issues here.

Public funded research gets outpriced for the end users who have contributed in no small measure to the same. They need to become more aware of these repercussions. Shrinking federal grants for public funded research means that there is no adequate oversight and auditing of the labs that are doing the same thing. These are potentially very high stakes, and patent awards can make individuals pretty rich.

I agree that these are generalisations and that this opinion isn’t set in stone. I have based the above assertion on my reading of the situation as well as verbal accounts.

What is urgently required is a partnership at all levels. It is to focus on one idea that has the potential to work in brain tumours. Pool in resources, under legal agreements, to work on the different aspects of the same problem. The idea above is more akin to a hub-and-spoke model of research. The goal is the identify molecular pathway and understand its implications for radiation therapy.

Let’s say, hypothetically, IDH gliomagenesis is the new pathway discovered. One team to work at a molecular level to identify potential inhibitory points, other to identify molecules that bring about this change. Another side to study the effect of radiation therapy and the pathway. Aggregated results would avoid duplication and overlap and lead to faster translational outcomes.

The problem is that they end up leaving radiation as an after-thought. It should change.

Size does matter

The size of clinical trials has now become a raging issue. I came across it on Twitter, and I’d like to put in my perspective to it.

The Wall Street Journal article presents a reasonably nuanced view about the need for trials. What it leaves out in the process is that some diseases like those involving brain, because of their relative rarity, would always need a clinical trial. Likewise, for common cancers arising in breast and prostate, the opinion for long-term clinical trials is divided because it is a significant public health problem.

The treatment protocols for brain tumours like gliomas hasn’t changed much in the past 15+ years. For even rarer diseases like CNS lymphomas, the role of chemotherapy has expanded manifold. Patients present to different facilities with varying standard of care. Not everyone has access to the “research facilities”, and especially in developing countries, that conceptual framework is non-existent. The treatment protocols are often the trial and error in what “fits” in with the Indian subset of patients. It is true primarily because out of pocket expenditure is a significant public health issue.

Now comes the emerging role of “personalised medicine” where the opinion for big or small trials is even more sharply divided. What everyone secretly agrees but never speaks out in the open? It is more important to understand the need to publish negative trials. The focus of the oncological community is towards the big bang positive studies; especially for the “blockbuster” drugs. These are often intricately linked to prevailing stock prices. There are perverse incentives as well, not to take the financial risks. It is the pharma companies that decide on “treatment protocols” and the “standard of care” where conflicts of interest are given short shrift in the protocols. That is the reason why I insist on public funding of trials where a leeway has to be made to fail. Previously, I have also argued that “personalised medicine” is way too much in its infancy. We are only nibbling at the outliers and nowhere near the core of the problem.

It is also incredibly naive to assume that if a company is offering an “unrestricted educational grant”, it has no say in the outcomes. It gets them a seat on the board to be able to influence the reports indirectly.

So does size matter? More extensive trials, are time honed but require immense resources. I strongly feel that hair-splitting in current treatment options offers no means to an end. Instead of a clear focus on the outliers (like the drugs), protocols need to include radiation therapy as an inherent component of treatment.

Translational medicine needs to become the centre-stage, and public funding should avoid a substantial scale duplication of work. It comes with its caveats.

Research in radiation oncology: Break the logjam

I came across this on Twitter (where else!) Despite the “weirdness” (pun intended), it was apparent that it raised substantial issues. I had responded to it, but it merited a blog post.

There has been an institutional push to observe and record in western countries. Higher disposable incomes with specific segments of society helped them to get a better education and as a result, better opportunities. It is not getting into a nuanced debate about the racial differences or affirmative action. Inequalities have always played a part but so is the ability to capitalise on opportunities that present itself.

A lot of research happens because of institutionalised mechanisms. The children have exposure to ideas from the school and paid internships, scholarships and grant opportunities. In India, the approach is entirely insular and works in silos. Medical science has grown incredibly complicated, and it is beyond the purview of anyone to grasp nuances of differentials.

As a result of those initiatives, a few developed economies have led and broken ground in “research” (whether it is transformational or applicable to real-world solutions is immaterial). It has spurred on the likes of China (an aspirational economy) to ape the same system led by the US, but rigid hierarchies stymie them. It is indeed laughable when Government of India decides to set up a “scientific officer for innovation” because it cannot happen in silos. Throwing money at central “research institutes” isn’t going to help because lack of real-world application has hardly moved the needle in any meaningful direction. Likewise, the research is mostly divorced from socio-cultural contexts.

We can only break the log-jam if we first identify the cause of the problem. Outsourced research to understand molecular pathways and then to apply developmental molecules for “blocking them” only perpetuates, what I call a scientific fraud of “monumental proportions” because of perverse incentives associated with “pharmaceuticals”.

(Radiation Therapy needs love- not in delivery methods but radiobiology and fractionation). It is sad that radiation oncologists have more faith and belief in “combination regimes”- altered fractionation schemes have been beneficial too. But progress is excruciatingly slow here.

It would be difficult to think beyond patent protections and intellectual property if someone else controls the purse strings.

Financial Disclosure: Much more than meets the eye

I have always wondered what the disclosures mean. Financial disclosure, to my understanding, means that no sums of money are involved in the publishing of the manuscript.

If a funding organisation has offered grants to a researcher that leads to publication, is the researcher acting as an “agent” of that organisation by researching what the agency wants?

There’s always an agenda.

Conflicts of interest sound more fanciful. It is a philosophical argument that seems like more of an afterthought and a subtle print as a footnote. I believe that most readers have turned a blind eye to this relative obscurity. I am also surprised that people in conferences often highlight this, but I digress. It is a matter of personal preference.

I think that the time has now come to be more comprehensive about the research agendas as well as identify motivation behind publications. This post was triggered by an innocuous write up in one “prestigious journal” where the lead author had pushed for a particular technological breakthrough in the healthcare system (Disclosure: I don’t want to highlight it for fear of reprisals!). One of the names that caught my eye was a company I had previously aliased. I was keen to bring in the same technology in India and report it’s suitability for Indian conditions. The executives decided not to implement it (and that’s another story!)

But how many people aware that the company in disclosure has precisely the same division working to popularise the health care intervention listed in the article? I have my genuine doubts because it is very niche.

Hint: Most users are unaware of who manufactures the innards of mobile devices.

I think it is time to explain these disclosures comprehensively in the context of the article.

Apple health: The new age digital colonialism

Mobile ecosystems have now boiled down mostly to a duopoly- Android and iOS. Android portrays itself to be an open source but now increasingly locked down by Google with incremental updates. Apple promotes its iOS operating system- increasingly popular with the physicians and lay people in developed and developing economies.

I am not delving into technical nuances, but perceived benefits of Apple are its flawed privacy stance based on its marketing spin called “differential privacy”. Apple hasn’t shown any inclination towards having any independent advertisement networks, and this division doesn’t get any mention. It gets it’s revenues from superior hardware and locked in services (these revenues are never repatriated back to the country of origin). Apple also has controversial policies concerning foreign workers in China, and the manufactured debate about the privacy (it fought FBI) was frivolous. It did divide the tech community. Interestingly, it’s foray in China is opposite of what it does in the US. It has handed over the encryption keys to Chinese government citing the local laws (paywall).

Personally, I find that their stance on privacy as a PR stunt. When I read or hear about their foray into healthcare, I recoil with horror. My privacy stance will not be enough to oppose them, but I was alerted to a write up in Harvard Business Review, which in my opinion, was a plug for Apple.

I can only surmise that interoperability within the electronic health records is a significant pain point. I know this because, at some point in time, I had been privy to getting one for my department. At the same time, my employer was keen to move towards it. (It did not materialise- but that’s another story). The question about the data portability came in, and it was apparent that it relied on some obscure protocol which didn’t have any open source equivalent. It meant that once the company goes belly up, all data, even if exported out, would only disappear into thin air. Or become useless.

Now you can foresee similar issues with the current tech companies. They would push for their proprietary protocols because big money lies in locking up users in their ecosystems. While the initial enthusiasm is understandable (a familiar user interface to work with like messaging applications) but it’s cheerleaders are ignoring the longer and more sinister implications of this move.

When the authors dream up instances of voice assistants detailing health information, I can only roll up my eyes. Either it is naïveté or stupidity or a mixture of both. These ancilliary companies are circling in anticipation of emerging technology, to feed on spoils from the ecosystem.

Is it suitable for the patients? Let’s examine that.

Healthcare data is most valuable commodity in dark web. Primarily, it has been used to impersonate individuals to gain access to medications (further sold in black markets). More importantly, healthcare data is of paramount importance- patterns of diseases, required interventions etc. should strictly be the purview of the governments and not private companies. None of which can be made accountable. The authors have explicitly mentioned about access to the third party companies where individual users are signing away the rights. The same consumers have been signing off the terms of services for Facebook, for example, and are shocked and horrified if they realise that their data is being used for psychological manipulation. People don’t recognise the importance of “caveat emptor”. Most users are technologically averse with very little understanding of the nuances involved.

Therefore, giving up data to these companies is a bad idea. I also see thought leaders and influencers pushing this line on the social media, but then, they have a lot to gain. I guess, no one reads the financial disclosures or stakes in the companies that stand to benefit from this push.

Healthcare and technology are getting more intertwined and complex. Let the likes of Apple and Amazon be excluded from this.

Or else, this would be the new wave of digital colonialism.

Open Source? Why does it matter?

I was alerted to a news about German Universities getting together and negotiating a national license with Elsevier.  This would be a fundamental game changer for Europe as well as rest of the world- for its huge implications.  My thoughts on this a little while later but consider this:

The institutions had formed a consortium to negotiate a nationwide licence with the publisher. They sought a collective deal that would give most scientists in Germany full online access to about 2,500 journals at about half the price that individual libraries have paid in the past.

Here’s what someone else has to say about this development:

Most papers are now freely available somewhere on the Internet, or else you might choose to work with preprint versions,” he says. “Clearly our negotiating position is strong. It is not clear that we want or need a paid extension of the old contracts.”

I am personally not getting in the politics of “open source”- its too contentious with proponents on both sides of the divide. Considering the fact that much of heavy lifting (peer review) is done free of cost; subtracting the administrative costs, publishing houses are left with profits. For someone who’s starting out, getting published in a marquee journal becomes almost “imperative”. Notwithstanding the “anonymous comments” that can be downright nasty!

The final word hasn’t been said as yet but lets wait for the outcomes. I hope they implement such a model in India as well- using a uniform log-in system to provide access. Its asinine to cough up over USD $30+ per article! Luckily, my institution does provide an access to Clinical Key but not all journals are available.

Is mandatory country repository a way out? No idea but its a logical extension that if public funding has been made available to researchers, the benefits should flow to public.

I am watching this space.