The possibility of new treatments in coming years that could, slow, halt, or reverse the progression of ALS demands advance planning across a wide range of issue areas and stakeholder groups. This paper reviews three of the most likely scenarios that new therapies could produce. It anticipates the impact of each scenario on ALS demographics, early detection, physician caseload, clinics and care services, fundraising, clinical trials, insurers and other sources of coverage, and on persons living with ALS (pALS), their caregivers (cALS), and their family finances.
It concludes that therapies that slow or halt the disease will produce major but manageable challenges to organizations dedicated to ALS care services, fundraising, research, and advocacy. Some of these challenges will require effective advanced planning to mitigate. Two of the most important emerging issues will include the need to develop much better early detection capacities, and the need for much higher levels of fundraising to cope with the dramatic increase in the number of people living with ALS.
Impact of therapies that slow or halt the progression of ALS on pALS, their caregivers, and their family finances will be highly variable, resulting in very positive outcomes and options for some, and very difficult choices for others about whether the new therapies’ benefits outweigh the costs.
A scenario in which a therapy reverses the symptoms of ALS for most or all pALS is obviously the most unambiguously positive and least complicated outcome. It will highlight the need to expand access, via international aid programs, to make the therapy affordable and accessible for the large and growing caseload of pALS in poorer countries. Advanced stages of the battle to defeat ALS will be waged in the global south.
With several drugs and treatments now in Phase 3 clinical trials, and more in the research pipeline, medical researchers are increasingly expressing hopes that we will soon see one or more new ALS therapies approved and available, possibly within the next two to three years.
This optimism comes with lots of anxieties and uncertainties – about which therapies or combinations of therapies will prove to be effective, when they will be available, what percentage of people with ALS (pALS) will respond well to them, how much they will cost, whether insurance companies will cover them, and what kind of impact they will have on disease progression.
The latter question is especially critical. Will the new therapies slow ALS progression? Halt it? Reverse it?
Whatever the case, more effective therapies are going to have wide-ranging impact — on pALS, on pALS’ families, and on the wider ALS support, care, advocacy, research, and coverage ecosystems. It is not too soon to start planning and preparing for all of the opportunities and challenges that new therapies will bring, even if the first new therapies are several years away.
These need to be frank discussions, because not all of the impacts of new therapies are going to be uniformly positive. We have to be ready to handle both the good and the bad.
The good news is that organizations involved in ALS work are already thinking ahead about some of these issues. The ALS Association convened a meeting in late October to bring together representatives from pharmaceutical companies, the FDA, and insurance companies – with some pALS representatives actively involved — to jumpstart discussions on questions of coverage of potential new therapies. This kind of forward thinking is crucial to help us get ahead of the curve on all of the issues that a new therapy will raise.
This paper is intended to anticipate the impacts of new therapies, based on three different scenarios. All of them over-simplify what will likely be a much messier reality. First, they assume uniform impact of new therapies, even though we know that variability of impact is much more likely, given the heterogeneity of the disease. Second, all refer to a single new therapy when we know that a more likely outcome will be an effective “cocktail of therapies” that will emerge gradually rather than all at once. And all are based on impacts in the US setting. In other countries with different health care systems and income levels, aspects of these scenarios could play out quite differently.
It should be noted that though these are presented as separate scenarios, they could, and probably will, occur sequentially.
The author welcomes suggestions for amending this first cut at an “impact inventory” and hopes to update the paper using reader feedback to improve the analysis.
Scenario 1: Slowing of progression
All of us living with ALS are hoping for new therapies that reverse the disease’s progression or even cure it. But we have to be prepared for more modest advances.
One possible outcome of this current round of new therapies could be a drug, a combination of drugs, or a gene therapy, that does not reverse the disease for most of us, but that significantly slows it down.
Let’s assume, for the sake of argument, that a therapy is approved by 2021 that on average halves the speed of progression. That will double the median, post-diagnosis life expectancy of people with ALS from 3 to 6 years. For pALS with slow progression, they could see their life expectancy leap from 7 to 14 years, or 10 to 20 years, or even more.
What are the implications?
ALS demographics. This will potentially double the number of people living with ALS. In the US, our numbers will quickly grow from 30,000 to 60,000, assuming most everyone has access to and uses the new therapy.
In fact, this could actually be a significant underestimation of the total number of cases. How so? The aging of the US (and global) population is expected to naturally increase the number of ALS cases in coming decades, even without any new therapies to slow the disease down. One recent study estimates a 69% increase in the number of people with ALS globally from 2016 to 2040 (from 223,000 to 337,000), solely based on aging of the population. Preparing for a sizable increase in the number of pALS seems prudent even if no new therapies are developed in coming years.
To borrow from the terminology of epidemiologists, ALS incidence rate (rate of occurrence of new cases, often expressed as the percentage of new cases of a disease per year per 100,000 people) will increase simply because of the aging population. The ALS prevalence rate (proportion of total cases in a population at a given time) will leap both because of the impact of the therapies that extend life expectancy, and because an aging population will produce more cases of ALS.
It is worth noting that this level of increase in the population of people with ALS in the US would not change the FDA and NIH’s categorization of ALS as a rare disease (defined as fewer than 200,000 affected by the disease), so ALS therapy development would continue to benefit from the provisions of the 1983 Orphan Drug Act.
Early detection. Drugs that significantly slow disease progression will have much more positive impact if paired with early detection, which has been a chronic problem with ALS diagnosis. The need for earlier detection will be urgent in this scenario. This will require primary physicians and neurologists to be better trained on ALS and made aware of the need for speed in diagnosis. If delayed diagnosis remains a problem, drugs that slow progression down will have limited impact, as they will simply arrive too late to extend life expectancy as much as they could. They will also miss the opportunity to extend the initial period of symptom onset, when symptoms are more mild and when pALS are most physically functional.
ALS physician caseload. For ALS neurologists, this scenario will, within four to five years, double the number of cases they have to carry. They could cope by reducing the number of annual consultations with pALS from quarterly to bi-annually. But how would that impact data collection, and quality of support to pALS, especially those who may not respond as well to the treatment? Another response could be policies to promote expansion of the number of newly trained neurologists who specialize in ALS. In the short term, do we have enough ALS specialists in the medical school pipeline to respond to heightened demand? Recent reports suggest that in the coming decade the US will actually be facing a serious shortage of doctors, so the odds of increasing the number of neurologists specializing in ALS may not be good. The physician caseload in this scenario looks to be a potentially serious bottleneck.
ALS inter-disciplinary clinics, and care and support services. For ALS interdisciplinary care and support work, this scenario will significantly increase demands on their services, doubling the requests for equipment, counseling, respiratory therapy, in-home care-giving, and other support. Rationing existing resources and care support would constitute a major drop in quality of care. Responding fully to new demands would require a major ratcheting up of fund-raising efforts, as well as an expansion of hiring of specialists and expansion of new clinics. The possibilities of harnessing new technologies to reach new pALS with telemedicine and virtual care could partially offset the spike in demand for care and support services, but would be no panacea.
Fundraising. The need to increase fund-raising for a doubling of care and support services will be acute. This will very likely exacerbate tensions between those who want to prioritize funding for research for a cure and those prioritizing fundraising for care services. Even though care services and research are much more closely interconnected than most of the public realizes, tensions over allocations of funds for research versus care services are real, and will be aggravated by a doubling in need for care services.
The solution — a successful ratcheting up of fundraising to fully meet all needs — is easier said than done. ALS competes with many other worthy charitable causes, and in the US total charitable giving has been flat despite a long period of economic expansion. Powerful public awareness campaigns will be required to explain why advances in ALS therapies are actually increasing the need for more funding.
Insurance companies, Medicare, Veteran’s Health Administration. For insurance companies, Medicare, and the Veteran’s Health Administration, the cost of new therapies and the doubling of patient life expectancy will create additional payouts, but given the relatively small number of cases this will not be a significant problem. The high cost per patient of ALS cases could, however, create pressure for cost control or create access problems. Some insurance companies could decline to cover expensive new “orphan drugs” if they have doubts about evidence of effectiveness.
Research and clinical trials. If most of the population of pALS is taking drugs that significantly slow down disease progression, how will this effect eligibility criteria for new clinical trials? Will it make it harder to discern positive impact of drugs in clinical trials? We know that slow progression cases tend to confound clinical trial results. In this scenario pretty much all pALS would become, to varying degrees, slow progression cases. This author is not expert on clinical trial design issues, so cedes the floor to others on this question. But it seems to be a question worth raising now.
The heightened importance for the need for early detection and screening will likely lead to calls for more research to advance that capacity.
Social Security disability insurance program. Our longer life expectancy could potentially raise questions as to whether newly diagnosed pALS should continue to receive expedited access to disability benefits, since at least some pALS will have the capacity to continue to work for a longer period of time (depending on their line of work and disease progression).
People with ALS, their caregivers, and their families. This is by far the biggest issue to consider.
First, the impact of this scenario on pALS, caregivers, and families will clearly be highly variable.
For some pALS in advanced stages of the disease, this scenario may be perceived to bring minimal benefits, as it will only prolong the most difficult, final phase of the disease when quality of life calculations can come into play. Some might have good reasons to want to extend their lives nonetheless — Stephen Hawking serves as a reminder that pALS who are entirely paralyzed can continue to pursue meaningful and productive lives. But some in late stages might forego treatment completely.
For most pALS and their caregivers, the benefit of living twice as long with the disease will be weighed against the doubling of the period of time of intensive, expensive home care for the pALS. This will put huge additional demands on caregivers, and huge additional expenses on family finances. A therapy that only slows the disease down could inadvertently produce a spike in ALS-related bankruptcies and could push some caregivers to the breaking point. Here we could expect to see a big split in choices based on household wealth. Those with ample resources will be in a better position to choose to extend their lives than those with modest resources.
The pALS who will stand to gain the most from this scenario are those in early stages of the disease, and those with slow progression. They will potentially be able to live many more years than they expected, and could remain in possession of most of their physical capacities for much longer. Some could live long enough to end up dying of other causes. Importantly, this scenario will also buy them more time to benefit from future medical breakthroughs that could reverse or cure ALS. But the flip side of the coin is the prospect of a very long period of partial or total incapacitation, with all of the difficulties that entails for the patient, the caregivers, and family finances. Some might opt for a two-track approach — taking the therapy during the period when they have retained most of their physical capacities, but then dropping it once they reach advanced stages of the disease.
Assessing Scenario #1. This scenario produces sizable but mostly manageable challenges for organizations involved in care, support, research on, and financial coverage of ALS. Impact on pALS and their caregivers will be more problematic and variable. The possibility of new therapies that significantly slow but do not halt or reverse ALS will be a positive development for some pALS, but a Faustian bargain for others. PALS and their caregivers and families already face very difficult and emotionally wrenching decisions on whether to use or forego procedures that extend life. This scenario will significantly increase the difficulty of weighing the costs and benefits of using therapies that extend life expectancy.
Scenario 2: Halting of progression
In this scenario, a new drug or combination of drugs effectively stops further disease progression, but does little or nothing to reverse damage already done. Everyone with ALS who gets this treatment must live with symptoms that are present at the time they start the new therapy. ALS is transformed from a fatal to a chronic disease.
What are the implications?
ALS demographics. In this scenario the total number of people living with ALS in the US will steadily increase by about 6,000 per year, less the (initially) small number who die of other causes – a number that will increase as the population of pALS ages. Moreover, as the American population ages (the total number of Americans over the age of 65 will double between now and 2060) the total number of new ALS cases is expected to rise well above 6,000 per year, increasing the number of people living with ALS even further. It would take a skilled team of demographers, epidemiologists, and statisticians to give us an accurate estimate of the total number of people living with ALS by 2040-2050 in this scenario. But we can all do a quick back-of-the-envelope rough estimate, and reach the conclusion that the number of people with ALS in the US could easily reach the hundreds of thousands.
Early detection. In this scenario early detection becomes an absolute priority. Every month of delayed diagnosis will mean permanent loss of some functionality for a person with early stage ALS, losses that could have been avoidable. Delayed diagnosis will be viewed as malpractice, not as an unfortunate reflection of the slow, “process of elimination” approach to determining if someone has ALS. Ideally, if advances in diagnostic tools are developed, detection will be done before patients even reach the diagnostic threshold, so that treatment can begin before symptoms appear or advance. Primary care physicians and other medical professionals who are often the first point of contact with people with possible ALS will need to be given much more training and guidance on referrals of possible ALS cases to specialists. Protocols might be needed to give possible but not definitive cases of ALS access to the therapy.
ALS physician caseload. The ALS caseload will explode in this scenario and will require a complete rethink of the current clinical support system. There is no way that the current system, which sees 20,000-25,000 cases, could shoulder several hundred thousand cases.
This potential crisis could be partially offset by the possibility that the new generation of “stabilized” pALS might not need to see an ALS specialist regularly, or even at all once diagnosed and given access to the new treatment. They could instead be monitored by their family physician and only referred to the ALS neurologist if their condition changed, if they experienced side effects from the therapy, or had other complications. This switch in the site of care and monitoring could erode or complicate data collection on ALS cases, and could require a rethink of the role of clinics in trials of new therapies.
ALS inter-disciplinary clinics, and care and support services. For ALS interdisciplinary care and support work, this scenario will create dramatic swings in demands for services over time. Initially, demand will be steady, since the number of ALS patients with moderate to advanced stages of the disease, now with much longer life expectancies, will go largely unchanged. Over time, the profile of the total ALS population will shift, with a declining percentage of pALS in moderate to advanced stages of the disease, and a rapidly growing percentage and number of pALS stabilized in early stages of the disease. The type of care required will shift accordingly, with more support to deal with partial loss of limb or voice strength, and far less need for support associated with advanced stages of the disease.
Fundraising. Fundraising for care services would initially need to be increased, then over time reduced, as the needs of the pALS population shifts almost entirely toward early onset issues. Fund-raising for screening and early detection services, and training of additional specialists for this task, will become a major new priority. Fundraising for research to reverse and cure the disease will also become a dominant priority. Whether fundraising becomes easier or harder in this scenario is hard to know, On the one hand, the success enjoyed by new therapies could create momentum for more support for research. On the other hand, it might become more difficult to argue that ALS is a top priority when the disease is transformed from a fatal to a chronic condition.
Insurance companies, Medicare, Veteran’s Health Administration. For insurance companies, Medicare, and the Veteran’s Health Administration, the high cost of new therapies combined with the exponential increase in people with ALS will constitute a significant expense, though the price of new therapies will presumably drop over time. Since most people with ALS in this scenario will be dealing with stable, early onset symptoms, many more will continue to be able to work, so a disproportionate percentage of the costs will fall on private insurance companies, not Medicare.
Research and clinical trials. If the population of pALS is using therapies that halt disease progression, eligibility criteria for new clinical trials will have to move away from the current practice restricting participants to those with fewer than 24 months since symptom onset. For some clinical trials, clean samples of pALS might be needed, which will pose a challenge.
Research to advance capacity for early screening and detection will be a high priority.
Social Security disability insurance program. Once pALS have a drug or drugs that stabilize their condition, and presuming most are diagnosed in time to minimize symptom onset, a much larger percentage of pALS will be able to continue to work, though some may have to find new lines of work depending on their condition. This would likely lead to pressure to eliminate the expedited access to disability benefits for pALS.
People with ALS, their caregivers, and their families. The impact on pALS and caregivers will vary dramatically by generation and income level. Those with advanced stages of disease progression at the time the new therapy is made available will only benefit if they have a powerful reason to want to continue to live despite severe physical constraints and if they have access to financial resources to cover costs of caregiving. For others with advanced progression, the therapy may not be an attractive option, though some might opt for it anyway in hopes of extending their lives long enough for a new therapy that reverses disease progression.
For pALS in early stages, suffering from only minor to moderate symptoms, this scenario is a life-saver, and almost all will seek access to the therapy.
PALS who are newly diagnosed after the new therapy is made available will constitute a new generation of pALS for whom the disease is chronic, and hopefully – if diagnoses are made early enough – featuring only mild and manageable symptoms such as foot drop or slight speech impediment. The entire profile of pALS will shift over time.
Assessing Scenario #2. The halting of ALS will lead to an explosion in the total number of people with ALS, place significant new demands on sources of health coverage, require much more capacity for early detection and diagnosis, and create changing demands over time on support and care agencies. For pALS with advanced disease progression, this scenario presents them with very difficult choices. For the rest of the pALS population, the rendering of ALS from a fatal to a chronic condition will be a welcome new lease on life, tempered only by frustrations over whatever physical abilities have been lost to the disease. Hopes and expectations that new therapies will be developed to reverse disease progression will be high.
Scenario 3. Reversal of progression
This is, of course, a happy scenario to contemplate. For pALS and their families and friends, a therapy that reverses progression to produce a (more or less) symptom-free form of ALS will be met with tremendous joy and relief. The gradual recovery of strength and physical capacity once lost to the disease will be a tremendous emotional journal for pALS (though it is possible pALS in advanced stages of the disease could suffer some irrecoverable losses in functionality).
Almost all US-based pALS, regardless of stages of progression or level of income, will benefit equally from the prospect of a therapy that reverses progression. The exception will be those without insurance, Medicare, or VA coverage, who, faced with exceptionally high costs of the therapy, could face the prospect of bankruptcy and loss of their home before qualifying for Medicaid. This is a potentially solvable problem, if the right legislation were passed or policies developed, and one that will demand close attention as a matter of equity and social justice.
What would be the wider impact of a therapy that reverses ALS progression?
ALS demographics. The population of people living with ALS in the US as a chronic, largely symptom-free condition will eventually grow to several hundred thousand.
Early detection. Early detection will no longer be as urgent, since symptoms are reversible. Delayed detection will constitute an inconvenience and annoyance for patients dealing with temporary unwanted symptoms.
ALS physician caseload. For ALS neurologists, their work will shift to confirming diagnosis and trouble-shooting cases of complications.
ALS inter-disciplinary clinics, and care and support services. Most ALS interdisciplinary care and support will gradually be rendered unnecessary. Those serving groups with other neurological conditions will simply shift their focus to those patients. The wild-card in this regard is the degree of variability of impact of new therapies. If not all pALS respond positively to the new therapies, care services will still be in demand, though at more modest levels.
Fundraising. Fund-raising might be needed to continue to support some research on the disease – mainly devoted to finding a cure — but that would be a lower priority compared to other medical research needs. Most of the organizations dedicated to fundraising for ALS will either close down or repurpose their mission, as the March of Dimes did once a polio vaccine was developed.
The wildcard in fundraising for ALS would be the possibility of a major shift in focus from domestic to international programming – an option considered below.
Insurance companies, Medicare, Veteran’s Health Administration. For insurance companies, Medicare, and the Veteran’s Health Administration, the cost of a new therapy required over the course of a lifetime, for hundreds of thousands of pALS, will be a significant new expense. Over time, presumably, the cost of the drug or therapy will drop.
Research and clinical trials. Research in pursuit of an actual cure for ALS will still be conducted, but most researchers in this scenario will move on to work on other medical research endeavors, as ALS research will likely be viewed as a less urgent priority by the NIH and other funding agencies.
Social Security disability insurance program. PALS will no longer have any need to go on long term disability, though some might require short term disability if serious symptoms presented themselves and diagnosis was slow.
Assessing Scenario #3. A cocktail of drugs and therapies that reverses ALS will produce almost all benefits and very manageable costs, mostly related to insurance coverage. This is a dream outcome, and is much less fraught and complicated than scenarios #1 and #2. Even those people who lose their source of employment in ALS fundraising, advocacy, and care service organizations and have to move on to tackle other diseases will take great satisfaction that they put themselves out of business by doing what they set out to do — defeating ALS.
But many of the current team of ALS advocates and fundraisers may not have to shift to another line of work; they will simply have to shift to a different target population. ALS is a global scourge, and will require a major global effort to treat populations in the global south who are far from medical support that can diagnose and treat ALS. The energies and expertise of people working on ALS in the American context could be put to excellent use in an expanded initiative to provide treatment globally.
It is worth briefly anticipating the implications of new therapies globally, especially in the global south, where most of the world’s people reside and where most of the cases of ALS exist.
One study (Arthur et al 2015) estimates that 223,000 people have ALS globally at this time, and that that number will increase 69% by 2040 even in the absence of a new therapy.
Three factors will drive this trend. First, the global population is growing at a rate of just over 1% per year, or 78 million people per year, almost exclusively in the global south. Second, life expectancy has increased dramatically in almost every country in the world, so many more people are now reaching ages when ALS is more common. Third, access to better medical care is improving globally, albeit unevenly, so we can expect that a greater percentage of people with ALS in the global south will soon be diagnosed properly.
The 2015 Arthur et al study observes that, without or without any new therapies, the weight of ALS “will shift away from the developed world towards developing countries.” It concludes that “[t]here are currently no studies outlining the cost of ALS in developing countries, and while economic costs are most likely lower in these locations, the increase in ALS cases will place an immense burden on their healthcare systems in the coming decades.”
Now, consider what would happen if a new therapy were made available globally that halted or reversed disease progression, and that most pALS who needed the treatment could access it. The global population of people living with a managed or symptom free form of ALS could grow about tenfold, to 3-4 million, by 2040.
But how will pALS in poor countries get access to new ALS therapies? The hurdles are daunting.
First, accurate and speedy diagnosis will be very difficult given the limited number of neurologists in the global south and the general lack of familiarity with rare diseases such as ALS among primary physicians. The wealthy cohort of people in the global south will stand a much better chance of correct diagnosis, but the rest of the population will face the risk of dying of ALS without ever knowing the true cause.
Second, even those who are diagnosed will face costs for therapies far beyond what most can afford and beyond what poor national health care systems can provide.
Third, calls for funding and support for ALS therapies will compete with demands for many other more endemic and more urgent health needs in the global south, and may not be a sufficiently high priority for some governments’ public health strategies.
The potential solution to these bottlenecks could be a much smaller variation of the global health initiative to combat HIV/AIDS. Since 2003, the US Agency for International Development has devoted $80 billion through the PEPFAR program to provide affordable, accessible treatment for people in the global south living with HIV/AIDS. It has saved an estimated 17 million lives in the process, rendering what was a fatal disease into a chronic one.
ALS organizations could play a critical role in international aid to raise awareness about, provide diagnoses for, and provide affordable access to therapies for populations in poorer countries of the world. This would be a hugely challenging assignment, but one which warrants preliminary planning now.
This paper is intended to jumpstart a conversation about how best to anticipate and plan for the impact of different ALS therapy scenarios. It is only a first cut at the topic, and an invitation to start a much wider and more thorough conversation.
Next steps could include:
- Collection of feedback on the draft, to revise the paper and make it into a more robust white paper on the topic for general use.
- Development of specific action items culled from the analysis.
- Proposals to convene stakeholders at workshops, virtual workshops, or in electronic forums, for targeted discussion of the most important action items stakeholders want to address for planning for each scenario.
- Agreement on a division of labor among the many ALS organizations for who plays the role of convener for which prioritized topics, to maximize inter-agency coordination and eliminate redundant efforts.
- Consideration of use of surveys as a tool to acquire better information on issue areas we feel are high priority but for which we lack solid data. This would be especially valuable in anticipating likely pALS responses to various options created by new therapies. This too would need to be a coordinated effort by ALS organizations, to avoid redundant surveys and the risk of survey fatigue among pALS and their caregivers.
Comments and suggestions are welcome – this is a living document and the author expects to update it. Send your comments to firstname.lastname@example.org . The analysis presented here is the author’s alone and does not necessarily reflect the positions of any of the ALS organizations with which he is associated. Many thanks to several colleagues who agreed to review draft versions of the paper and who provided very helpful comments.