Elementary, my dear Watson

One of the enduring mysteries in Arthur Conan Doyle’s delightful Holme’s series is that whether Watson was needed at all. However, it transpires in the text that Watson is more like a second person to whom Holmes is speaking with (much like a sounding board).

Purists although would point out the truth hiding in plain sight.

In real life, the modern day Watson is far from perfect, and its cheerleaders sound even dumber.

In a scathing write up in Wall Street Journal, the reporters have laid bare the hype behind IBM Watson that was supposed to have revolutionised cancer treatment. Doctors from a reputed hospital joined the project to “provide direction” followed by a series of photo-ops. The word out was that we were, at last, on the brink of revolutionising the healthcare as we knew it.

To cut a long story short, it didn’t happen. It was being used for marketing by prominent hospital chains with “opinions” sought from the “latest literature”. There is NO scientific evidence that it made an iota of difference.

I have no idea what is the problem that they were trying to solve in the first place. Everything is available off the shelf, and it is incredibly easy to start off a chemotherapy regime. The promised efficiencies of the scale never materialised. Watson was supposed to tap into existing electronic medical records so that it can pre-fill and auto-populate the fields. However, these are limited to restricted geographies and hence do not have worldwide relevance. They do not have a mechanism to quantify the outcomes and measure responses. How would they know what works and what doesn’t? If the results have to be determined by the clinician, what is the point of having this expensive system in the first place? Another issue with it is its poor adaption to clinical ontology. I have seen and heard about the way it struggles with building up the “clinical dictionary” that makes it difficult for it to adapt to hand-written notes. It is likely to lose out all the context of patient’s clinical history. How accurate would its recommendation be if there are significant gaps in the patient’s verbal history? Clinicians often make educated guesses and implied understanding of patient’s issues.

I remain sceptical about the broad-based “research” that multinational corporations push out. There seems to be no truth in the advertising. The original biomedical research has plateaued concerning outcomes. If we have run out of targets, we dig deeper to find new ones! How much do we need to “understand” about pathogenesis? Let us find something worthwhile from what we have discovered. We require an audit of existing “research” to prevent overlaps.

Instead, we need similar and parallel approaches in patient support and ancillary services. The use of mobile technology with adequate privacy safeguards to assist affected patients is promising.

Even from the perspective of Radiation Oncology, we need more to understand this fascinating science. Radiation Biology hardly ever scores funding; for example, we need a scoring system to quantify plans and qualitative analysis for clinical outcomes. We also lack standards to match it with reported clinical results.

The undue focus on the biomedical research will rob us away from our real targets- the patients. In the quest for mutations, we forget its the real people who need good palliative care and support system.

Imagine, if we could channelise the millions of dollars for something constructive! I strongly feel that it is a wasted effort. AI in healthcare can wait.

Achieving the digital detox.

Over the past few months, during my interaction with various people on Twitter and offline, I have been hearing about the information deluge that makes it impossible for them to acquire new skills. We indeed have limited 24 hours!

I wouldn’t be able to give a blow by blow account of how I manage things, but I have had to stick to certain good habits that have made things more comfortable for me. I will mention a few services below that make it incredibly easy to flow past the flood of distractions.

1) Mobile phone:

This is the biggest annoyance! I am off the social networks on the device barring Telegram. More on that later.

Twitter is accessed only on the browser. No dedicated applications exist. All notifications on the device are blocked except for text messages.

Telegram helps me to mute all conversations except people whom I deem essential. I have a lot of channels where I consume content passively. No mainstream social networks like Facebook or Instagram for me. They are antiquated because I cannot control them.

I also don’t have a fear of missing out. My associates either call me or text me if needed. Android has become better to manage notifications in recent times. I don’t have any experience with iOS, but I remain convinced that Apple iPhones are merely iPods with a calling facility.

2) Email.

I had mentioned this earlier too. I use Fastmail because I find there is inherent value in paying up for the email. I use a lot of aliases whenever I sign up for the service. It helps to signup with a unique email address. For example, for Dropbox, my alias will be dropbox (at) FastMail dot com (it is a hypothetical- just for illustration). Therefore, if any spam flows into my inbox, I know where is the leak from. All I have to do is to delete the alias.

This simple hack has served me well over six years, and I am happy to stay with this service. Mainstream email applications like Gmail or Yahoo are useless.

I have also created extensive rules which directs the email in the trash. It helps to clean up the clutter at the server itself without manual intervention. For example, all newsletters go to trash directly. Some of them are automatically marked as read and stay in the inbox- I scan through them when I get time. When they are marked as read, I don’t get a notification. Therefore, can easily stay focused on my work without being distracted by the flow in the inbox.

3) Password Manager

1Password is the password manager that is my life saver. It generates unique passwords for all the websites. It is a paid service, but good cloud sync helps me to sync it with my Android device as well. It eliminates the need to remember unique passwords.

4) The use of Telegram chat app

Telegram remains the only way to stay connected with any semblance of “social network”. I use a combination of groups and channels to stay informed. Channels work as public broadcasts. Any specific information I need is transmitted to it. I use bots (both paid and free) to achieve the effect.

For example, I use the IFTTT bot to work with the RSS feeds to populate the channels with the Pubmed content. If I need to track, say the latest publications in the development of MR-LINAC, I don’t have to visit the website manually. By use of booleans, I can filter the content, generate the specific RSS feeds which pipes it elegantly in the channel via IFTTT bot. Likewise, I use junction-connection bot and Feed-Reader bot for different purposes. I pool in information from all specific channels I need to follow into one omnibus channel so that I don’t have to deal with a multitude of channels. I do this by using junction-bot on Telegram.

Feed-Reader bot helps me to tap into various other social networks. For example, I have a specific channel devoted to cycling. All posts from multiple Instagram accounts flow in the channel. It helps me to keep track of the sectoral development. Likewise, I developed a channel for journalists on Telegram to keep track of telecom sector and clean energy. I also have a dedicated art channel that I helped to make for a friend. That collects all impressionist art, beautiful nature pictures and graffiti! None of the posts is done manually.

Focused groups require extensive group management. I recommend using Combot because it comes with a beautiful web-interface. Although the community bot management has introduced a paid plan, it is free for groups that have up to 100 members. The bot deletes specific stop words automatically along with other nifty features like muting users. The bot also keeps groups free of spam messages. Therefore, the groups stay efficient, productive and on course. It is unlike WhatsApp where users start spamming others without any rhyme or reason.

This above may sound onerous, but it helps to maximise the efficiency gains. As long as you are not distracted, it helps to keep focused on work.

In the busy schedules that we keep, always find time for solitude. That is the most critical period to stop and reflect on your goals.

Digital tools need a constant refinement. Hopefully, I will update this in the future.

(Images are for representational purpose only. This blog post is not intended for any commercial purpose).

Biomedical research, outcomes and survivorship

This post was the result of being tagged in an interesting discussion on Twitter about survivorship. I want to give in my viewpoint.

Survivorship isn’t just about a hard clinical outcome. It is about the functional autonomy of an individual. There are various issues tied up here; it wouldn’t be appropriate to discuss survivorship issues in isolation. I would, of course, take the example of brain tumours per se and weave in the narrative for various interconnected problems. I have been thinking about it for the past two weeks and here’s my observation.

I was lucky to attend Paediatric Neurooncology conference- which was my first trip to States. It had been a fantastic experience; great organisation as well as well attendees from different parts of the world. However, one thing stood out- the predominance of biomedical research. I wouldn’t hesitate to call it as vanity research because it is an arms race to practically nowhere. We have expended billions of dollars in hair-splitting pathways and identifying newer targets, but as an opportunity cost (investment versus tangible outcomes) it is a downward spiral and a wasted opportunity. I am not advocating less of research but one that has measurable practical results.

Let’s look at survivorship from three examples. Meningiomas, Medulloblastomas and DIPG (as the extreme). Meningiomas are mostly indolent but are considered “curable” after definitive surgery followed by an indication for radiation therapy. How and why the need for drugs has come in? What proportion of patients needs it? Are they effective? And if the disease is aggressive and progressive, when do we call it a day and suggest best supportive care for the patient? The hapless patient would need dependent care (based on what neurological functions have deteriorated). How do we define survivorship here? Have we made the patient functionally autonomous or helped the patient to adjust to the disabilities?

The “middle rung” (as I would call it because it has a decent prognosis) is medulloblastomas. Elegant research has divided this into various subtypes with the promise of “de-escalation” of treatment. How much, do we know that “less is less” and not “really less” of radiation therapy? Chemotherapy, from the classical radiobiological constructs, eliminates only the most active cell populations but still, the “spurters” remain in the cell pool. Reducing the radiation dose will, in all probability, really compromise with the eradication. The “myth” of radiation-induced side effects continues to this day without really accounting for the long-term neurocognitive effects of chemotherapy.

What is survivorship in this context?

The last but not the least is relative rare diffuse intrapontine glioma. This diagnosis is universally fatal, and despite an intense outpouring of research, the outcomes haven’t improved. They have drilled catheters to deliver drugs right at the source and have claimed “success”, but the overall scenario remains bleak. What is survivorship here for DIPG?

Hence, either way, you look at it, there are no easy answers. The spurt of biomedical research (often cornering the most significant resource) needs to be tempered with the realistic expectations of the pharmaceutical industry (that funnelled research into practical, actionable targets). There have been clamours, of course, for a “close collaboration” between the industry and academia but everyone is aware of the pot of gold. An actionable mutation followed by a drug and patent protection for about ten years is equal to profits. Insane profits. But, how has survivorship improved? Instead, we have newer metrics to measure “survival” like “progression-free intervals” which has no meaning because the disease is always present.

I feel that it is important to pay equal importance to the emerging role of technology and patient support. Like the innovative use of chat applications, the emergence of bots and various platforms that can make life easier to adjust with disabilities. Patient support is an ignored criterion that could get a better impetus and more funding to make lives more meaningful.

The central question remains- when to introduce “palliative care” and “hospice” in the evolution of the disease. These two questions determine the meaningful survivorship.

As from the preceding discussion, it is not easy to quantify survivorship. The goal of research should remain improvement in population outcomes. Cancer aetiology points out towards mostly preventable causes- air pollution, smoking etc. What are we doing to improve our score in that direction?

Last but not the least is cancer prevention. Sadly, it is not relevant for gliomas save for the fact that mobile phones are “probably” a risk factor. That opens up another can of worms because industry-sponsored research fails to show an association between exposure and disease. Oh well, I am not surprised there.

Lets put things in perspective. We are trapped in our web of confirmation biases. Let’s focus on better ideas (pardon my cliche) for “cross-pollination” of disciplines. Radiation Therapy is curative and is the most critical determinator of survivorship.

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.

My Twitter journey so far

It is an honest confession about what I have been able to achieve and put it in perspective. Is the social microblogging website, beneficial?

  1. I have been lucky to come across many excellent individuals! Medical Physicists, Radiation Oncologists and the fraternity which gets together and deliberates on matters of mutual interest.
  2. I had to use a lot of muted words because most people don’t realise that Twitter is meant for “manufactured outrage”. It is lazy person’s means of “activism”.
  3. I follow many accounts, but some of them are muted because their tweets add no value to the discourse here.
  4. Some Twitter users are great. They read whats on their platter, but Twitter sorts out interaction based on algorithms. It means you are likely to miss out on a lot of important things. Your likes, re-tweets or other signals are factored in what you ultimately see. It isn’t educative nor informative.
  5. I participated in my first virtual conference for ESTRO. It was an enjoyable experience, and I have written and shared my ideas extensively. If you wish to factor in Twitter as part of an interactive platform, you need to have a coherent strategy. A generic hashtag adds little value to the overwhelming noise. I would, on any given day, have a Telegram channel, instead.
  6. I am dismayed by the constant barrage of advertisements by many organisations. It is good to promote diversity of thought; however, it is clear that these accounts have been outsourced to different agencies. It appears phoney; as if they are drunk of kool-aid. My bullshit filters typically go up at the very thought. I am not naming them, of course, but it gets my goat. Likewise, for a respected “physician-scientist”. It may be acceptable to make political statements, but it is like mixing wine with water. The result- academics+politics doesn’t make any sense.
  7. Gender politics on Twitter is too stupefying; I am gender neutral (if that is the term) and I prefer to see individuals as such. There is no meaning of gender for me (as far as academics is concerned). Using your Twitter account to wash your dirty linen in public (because you have a specific gender) is labelling your back with the tag of “stupid”. Ultimately, it is your choice as to what you wish to achieve with social media. I usually prefer to stick to a personal account on Twitter or better still; I prefer Telegram.
  8. The click-through rate for articles is abysmal. If you wish to see an improved version of click-throughs for the posted links, you will need to have a large number of followers.

Has there been any luck with getting people to switch over to Telegram? Nope. Nada. Zilch. It is because of my tacit understanding as follows- Twitter as a medium for beginners is intimidating. Many users prefer to stick with the known than to start with something new. It is not laziness, but everyone has a motive to be online using Twitter. Some wish to have a more significant exposure; some users want to interact with peers, some want to express outrage or crib about life’s not fair. There is no one reason. Telegram is much more personal compared to Twitter. I have a couple of groups and channels with me on Telegram. It is good to spend time by consuming content passively. Groups allow more fine-grained control and better-nuanced interaction. And the recent moves by Twitter to force users to access it through web-alone is a stupid move.

Twitter is a bitter-sweet experience. Yes, the constant stream can be tiring and distract you cognitively but it is fun in parts. On the flip side, you end up meeting amazing individuals and people from different departments across the world.

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.