Personalized Medicine and Public Good: 3 Critical Issues (Part 2 by Johnathan Ng)

This article is the second part in a two-part series by Dr Johnathan Ng of Epibone, on personalized medicine and public good.

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Personalized Medicine and Public Good: 3 Issues that Must Be Tackled

In my first article, I gave an overview of personalized medicine: personalized disease-modifying drugs, autologous cell therapies and stem cell therapies.

It is easy to be swept away by the promises of precision medicine. In his speech on the Precision Medicine Initiative, then-President Obama made uplifting points, “And that’s the promise of precision medicine – delivering the right treatments, at the right time, every time to the right person… we want to have a nation in which the accidents and circumstances of our birth aren’t determining our fate, and therefore born with a particular disease or a particular genetic makeup that makes us more vulnerable to something; that that’s not our destiny, that’s not our fate – that we can remake it.” 

Indeed, the potential benefits are tremendous, but so are the risks: in the form of escalating medical bills, with unproven – or worse still – harmful treatments. In this article, I give Governments and Healthcare providers three areas to pay attention to when it comes to personalized medicine: Regulation,  Healthcare Finance, and democratizing the benefits of personalized medicine.

  1. New Pressures on Regulation

As new personalized treatment modalities emerge, regulators are facing increasing pressure to green-light interventions, even if clinical benefits are not clear – to provide patients with a chance to live.

A watershed case was the US Food and Drug Administration (FDA)’s ruling against a scientific advisory panel, in favor of patient advocacy groups to approve Exondys 51 marketed by Sarepta for treating Duchenne Muscular Dystrophy. Despite a majority (7 to 6) of the experts citing inadequate convincing clinical evidence, the FDA director greenlit the approval of Exondys 51 due to a lack of clinical alternatives. Many commentators felt that this case set a precedent for the approval of personalized medicine products based on surrogate endpoints without clinical benefits.

There are also many grey areas when it comes to regulating clinical trials. As with any emerging technology, the benefits come at a risk, which people desperate for a cure may be willing to take. Due to the exploratory nature of trials involving new treatment modalities, patient safety is often left in the hands of researchers: a simple search on ClinicalTrials.gov shows nearly 6000 clinical studies involving stem cells, some of which have not been approved.

Some of these trials have resulted in debilitating consequences. For example, severe adverse effects, some resulting in death, turned the spotlight on Juno Therapeutics’ lead CAR-T cell therapy for treating adults with late stage acute lymphoblastic leukemia. The risks of stem cell therapy are also not well understood. Although treatment with autologous fat-derived stem cells has been used for various indications, a poorly administered trial recently led to permanent eye damage in three elderly patients with macular degeneration (damage to parts of the retina in one’s eye).

Without proper regulation and well-controlled clinical trials, the safety and efficacy of stem cell treatments cannot be determined.

Some researchers show more caution than others. In the first human trial that uses an induced pluripotent stem cells (iPSCs) derivative, investigators from Japan successfully treated macular degeneration  by administering retinal pigment epithelial cells grown from the patients’ own stem cells. Yet, after identifying a few mutations in the second patient’s cells, the RIKEN group decided to suspend the trial in September 2015 before obtaining clearance from health authorities in Japan to resume in February 2017. Perhaps all scientists and clinicians would do well to hold themselves to a similar standard.

Regulatory bodies such as the FDA must continually engage and balance the needs of the scientific, patients, and clinical communities in meeting these new regulatory challenges – unfortunately, there are no easy answers.

2. New Pressures on Healthcare Finance

With the flood of new interventions, another issue to consider is cost. If all interventions are fully reimbursed (i.e. paid for) by state and private payers, the healthcare system will soon become bankrupt. Yet, if no help is given, the cost to patients of living longer is bankruptcy. The American Society for Clinical Oncology (ASCO) wrote in a brief that a patient living with cancer is now three times more likely to file for bankruptcy than a healthy person.

Policymakers must strike a fine balance of curbing the rapid rise in healthcare spending without disincentivizing innovation and depriving patients of access to life saving treatments.

When weighing the clinical benefits of a new drug product with the cost, healthcare economists typically apply a measure called the incremental cost effectiveness ratio (ICER) which takes the difference in cost between the new drug and existing alternatives and divides it by the change in quality adjusted life years (QALY). The National Institute for Health and Clinical Excellence (NICE) of the U.K., for example, sets an ICER limit of £30,000 per QALY gained for new drugs including targeted therapies. Most policymakers in the U.S. generally apply an ICER limit of USD$50,000 per QALY gained.

Early evidence suggests that personalized medicine tests are generally cost effective, with 20% of them resulting in cost saving and more than half achieving ICER of less than $50,000 per QALY gained. However, measures of cost effectiveness apply a single threshold to a heterogeneous population. If reimbursement was based on this alone, some people would receive more healthcare than they would choose, and others less. As such, commentators have noted that “reimbursement mechanisms for targeted therapies are still very blunt in an era of personalized medicine”.

Policymakers must leverage data and work with other stakeholders to improve reimbursement policies, especially taking into consideration the underserved population. Yet, the onus does not belong to the policymakers alone. Drugmakers, payers and clinicians are very much involved in the determining how drugs are priced and reimbursed. Recently, there have been exhortations by clinicians for more value-based pricing whereby reimbursement is contingent upon patient outcomes. The focus on outcomes could ensure that personalized medicine realizes its full clinical value. To achieve that, drugmakers could enter risk-sharing agreements with payers for partial reimbursement prior to demonstrating clinical effectiveness.

Alternatively, clinicians can also exert pricing pressure on drugmakers indirectly. In 2012, researchers from Memorial Sloan Kettering Cancer Center (MSK) evaluated the drugs Zaltrap and Avastin for treating colorectal cancer. Although Zaltrap cost twice as much as Avastin, the MSK researchers found no differences in efficacy between the drugs. Consequently, MSK decided to not recommend Zaltrap to patients and this led the drug’s co-marketer Sanofi to drop the price.

Together, stakeholders can work to ensure that personalized medicine is conscionable and cost effective.

3. Democratizing the impacts of Personalised Medicine

Finally, perhaps personalized medicine should be about more than just the diagnosis and the cure. Personalized medicine could go a long way towards disease prevention and mitigation by engaging the laymen and teaching them to monitor and manage their own health. In a recent trip with my parents to their dental appointment at a polyclinic in Singapore, I could not help but notice that the Health Promotion Board set up a booth that encouraged senior citizens to get screened for colorectal cancer. Participants were instructed to fill out their information, collect samples of their stool at home in the kits provided, and send the kits back for analyses. Though seemingly mundane, campaigns like this are probably the most effective way of bringing personalized medicine to the masses.

Low cost point-of-care diagnostics can also help to bridge the divide between first world medicine and third world need for solutions. After all, if the goal of personalized medicine is to understand and improve lives, esoteric treatments will hardly do a majority of the public any good.

Finally, it is a positive development that countries are thinking about how to democratize the benefits of personalized medicine. For example, the U.S. National Institute of Health is collecting data from underserved populations that are historically underrepresented in biomedical research, so that they too can benefit from personalized medicine.

In conclusion

We have already seen the good that personalized medicine can do. Yet, if we want the broader public to benefit from personalized medicine while minimizing both the financial and clinical risks to society and patients, there is still so much more that we must do. Stakeholders must continue working together to advance the personalization of medicine, not for fame or fortune, but for the greater good.

Johnathan Ng
Thanks, Johnny!

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Thanks for reading this two-part series on personalized medicine and public good. When I started this blog, one objective was to use it as platform for issue-experts in technology fields to give us mini crash-courses, and to sketch out the implications for society. I am sure Johnathan will be more than happy to discuss these issues further. Let me know if you’d like to be connected!

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Better Consumer Access AND System-level Sustainability: Can Cities Have Both?

 

This week I read three parallel articles: one on healthcare, two on transport, all with the same theme: how the introduction of disruptive technology in traditional ‘public services’ led to a flood of new demand, calling sustainability into question.

I’ve thus far painted a positive picture of how new technologies can democratize access to services: Riding in the comfort of a private vehicle is no longer restricted to those who have money to own a car. Tele-health, where patients can consult their doctors online rather than face-to-face, is cheaper and more accessible than a traditional doctor’s visit, cutting down unnecessary waiting and travelling time (issues that disproportionately affect the poor and elderly!).

But improving access often leads to a surge in demand, creating new problems for society. These articles point towards an important trade-off between consumer access and system-level health that I haven’t quite addressed. [Spoiler alert: we should care about both because they are ultimately about the consumer!]

Transport

“The Downside of Ride-Hailing: New York City Gridlock” empirically shows how ride sharing has worsened congestion in NYC because many have replaced their subway rides with an Uber or Lyft. “Average travel speeds in the heart of Manhattan dropped to about 8.1 miles per hour last year, down about 12 percent from 2010”. New Yorkers have famously pushed back against their Mayor’s attempts to restrict the number of Uber cars.

“Autonomous Vehicles: Hype and Potential” shows how autonomous vehicles can also exacerbate traffic congestion, slowing down the movement of people and goods around the city.

  • One of the promises of autonomy is that the car can be re-imagined. IDEO imagined how cars might become work-spaces in the picture below. Once the car becomes a comfortable place to work or relax, many of us might not mind spending more time on the roads. I might opt for an Uberpool even if takes twice the time of a train journey because it’s such a comfortable, productive ride.
  • If these autonomous vehicles are privately owned, people might send their cars on trips they would normally take. For example, sending their car to the McDonald’s drive-through, or far out of the city center to find cheap parking.
  • We will also take some time to get to roads where vehicles are 100% autonomous. In the interim, human drivers are likely to “bully” autonomous vehicles because they know that these autonomous vehicles are programmed to be risk-averse (an autonomous vehicle killing a person is perceived as a greater travesty than a distracted driver killing a person). In such a scenario, we will see autonomous vehicles driving at slower-than optimal speeds, creating more congestion.

Source: IDEO

Autonomous work spaces

Healthcare

The parallel in the healthcare system is a study by RAND Corporation, showing how only 12% of tele-health visits have replaced visits to the doctor, while 88% represented new use of medical services. Unsurprisingly, this finding suggests that doctors’ visits are highly price-elastic – by halving the cost, we see a surge in new demand. Net annual spending on healthcare among patients with respiratory illnesses increased by US$45 per tele-health user.

This is a bigger problem if the new users actually didn’t need to see a doctor and a smaller one if they would have deteriorated if not for the medical treatment. The answer is likely somewhere in between – I believe closer to the former – 88% is huge (But a more in-depth study correlating the new use of medical services with health outcomes is needed). There is potential for tremendous waste in our already-stretched healthcare systems if we massively lower the cost of healthcare services without creating disincentives for unnecessary usage.

How can we get the best of both worlds: access and sustainability?

Technologies have amazing potential to help us use scarce resources like doctors’ time and road space more efficiently, creating greater supply. By lowering cost, they also ensure that this greater supply is spread out more evenly across the population, regardless of income.

However, doctors’ time and road space are ultimately still scarce resources that need to be rationed somehow. Capitalist countries are happy to ration these services by income. Countries on the socialist end of the spectrum (think the UK National Health System) tend to ration by waiting time. Neither fully takes into account the most important consideration: need and urgency.

How can we incentivize people to only use these new, accessible services only when they really need it? Here are some ideas.

In transportation

In transportation, cities need to make mass people-mover systems (trains, buses) the core service used by most commuters: ride-sharing must complement, not replace trains and buses. The bulk of commuters should spend most of their journey in trains and buses where the road space per commuter is significantly lower. Ride-sharing can be a first-mile and last-mile solution (e.g. home to train station), but certainly not the default for the whole journey.

To achieve this, cities need to up their game in public transportation. It has to at least be reliable and predictable (which many, many aren’t). Examples of how Singapore has done this here and here. Taking a step further, payments and arrival/departure times should be integrated with ride-sharing platforms so that people can minimize waiting and inconvenience when transiting between ride-sharing and public transportation. Work-friendly design in public transportation (think flip-out work tables in public buses) will also help make these options less unattractive compared to IDEO’s self-driving pods.

When it comes to autonomy, cities also need to think about moving to 100% autonomous vehicles as quickly as possible, since the dynamics between human drivers and autonomous cars will likely increase congestion. A 100% autonomous vehicle scenario also creates the most gains in efficiency and safety – vehicles can travel bumper to bumper (more efficient use of roads) and provide information to each other about road and traffic conditions (safety and efficiency are both enhanced). I cover some strategies in this article though this is a topic worth exploring in greater depth.

Finally, slightly more “interventionist” policies may be needed, such as limiting private-use autonomous vehicles and rationing the total number of cars dedicated to ride sharing so that people are prodded towards mass people-mover systems like trains and buses.

Tech companies sometimes paint these suggestions as the Government acting against the consumer interest. I disagree: it is in the commuter and patients’ interest if we can manage the demands on our roads and doctors such that those who need it most can get the services in an affordable and timely manner.

In healthcare

In healthcare, raising co-payments is a commonly-used tool which helps people think twice before using a service. “Triaging” patients is another way – for example, having them first speak to a nurse practitioner and only passing them to the doctors if it is needed.

But let’s take the patient’s perspective for a minute. What’s motivating them to use a service they may not need? Anxiety that their condition may be more serious than they think, and lack of a place to clarify (short of calling up a doctor). Any new parent empathizes with this. I probably went to the doctor every week in the first month of my daughter’s birth for no good reason at all.

We need solutions that assuage a patients’ anxiety. I believe equipping home caregivers is going to be a big part of this. Home caregiving is currently an informal sector with minimal training, which is an incredible waste. Imagine if home caregivers could be the first line of defence – giving the patient assurance when they do not need a doctor, and quickly helping them access a doctors’ time when it is urgent.

If healthcare systems and healthcare insurance providers want to use tele-health to optimise their use of resources, the technology has to be complemented by human-centred solutions that assuage patients’ anxiety. If not, the technology won’t save them any money at all!

Conclusion

I hope that with the addition of this article, I’ve now painted a fuller picture of the impact of disruptive technologies on public services like transportation and healthcare. Indeed, they will make resources more abundant and accessible to people with lower-incomes. However, complementary policies and services are absolutely necessary to ensure that the system is not over-used – ultimately, so that those who really need the services can get it in both a timely and affordable manner.