5) Challenge Programmes

Part 5 of the 12-part series - 'A Grand Machine to Beat Covid-19' - zeroes in on an example Challenge Programme, focussing on innovating new medical treatments for C-19.

The MMM approach is especially well-suited to the development of treatments and vaccines. Applying Challenge-structured innovation, multi-dimensional crowdsourcing, and third-party scientific evaluation, within the field of pharmaceutical R+D has particularly interesting ramifications.

Pharmaceutical Development

Before investigating this, let’s simplistically summarise the traditional process for developing new treatment therapies:

1. Drug Discovery – identifying and developing new chemicals and compounds… the most promising ‘Clinical Candidate’ drug therapies are taken forward for testing

2. Test-tube-based testing (can blur into previous step)

3. Animal-based testing

4. Testing on small group of humans – Stage 1 Clinical Trial

5. Testing on mid-sized group of humans – Stage 2 Clinical Trial

6. Testing on large group of humans – Stage 3 Clinical Trial

7. Official licensing for successful treatments

8. Monitoring continues as treatment rolls out – Stage 4 Clinical Trial

Pharmaceutical companies employ a team of professional scientists to select the best candidate drugs and methodically go through these steps, generally using resources internal to the organisation, but outsourcing clinical trials to specialist companies. It’s a long, expensive procedure… especially the task of implementing the new treatment on thousands of volunteers. The whole process is strictly-regulated, takes over a decade, costs a couple of billion dollars, and the majority of trials fail to produce an effective therapy.

To make back the vast amounts they’ve invested in drug development, pharmaceutical companies need to earn as much as possible from their (relatively-few) successful therapies. Unfortunately, the current system only enables them to do this, by granting the corporations monopolised intellectual property rights – preventing others from competitively producing the drugs, so they can be sold at a price far above production costs. To make matters worse, because the private IP is worth far less than the real value of the associated innovation, patent rewards represent an inadequate incentive to invest in R+D in the first place.

This is not the most efficient system at the best of times.

Treatment Challenge Programme

Now let’s explore the MMM approach, taking the example of the hypothetical ‘Treatment Challenge Programme’ – focussed on innovating therapies to alleviate severe C-19 symptoms. Instead of a team of directly-employed scientists (and an outsourced specialist) taking a drug through all eight steps, the process is divided up mass-production-style to test a large number of drugs, all at once. The steps are separated out, with each stage of testing conducted at maximum scale and teams of directly-employed scientists collaborating with the MMM cogs every step of the way. Essentially, the Machine tests all pharmaceutical technologies together in one gigantic Mega-Trial.

Every existing treatment we have, that has reasonable potential to be retargeted at C-19, should go straight into the Mega-Trial Mainstream (equivalent to a Stage 3 / 4 Clinical Trial) for rigorous assessment. Teams of professional scientists and health-workers are deployed to carry out the tests, overseen by esteemed scientific institutions. Volunteers are gathered through the platform (mostly via hospital doctors), with the enormous scale of the Machine enabling this to be done with maximum efficiency.

Therapies are assessed according to key criteria, including: mortality rate, medical outcomes, time-to-recovery, cost-per-patient, ease-of-application, impact of side-effects, etc. The nature of the system enables the collection of top-quality control-group and baseline data. As with all Challenges, results and information are displayed openly, as soon as reasonably possible, with a live leader-board highlighting the most-promising treatments.

We’ve already made good progress, repurposing and testing our existing drugs, but tackling C-19 will inevitably involve discovering and developing new pharmaceuticals. Therefore, the ‘Treatment Drug Discovery Challenge’ is one of the key competitions within the ‘Treatment Challenge Programme’. Innovators are invited to submit clinical candidate pharmaceuticals and to provide arguments and evidence to support their suggestions.

Challengers can make use of the vast quantities of information and data, knowledge and innovation, churning out of the Machine. Especially useful is the searchable database of all the research that’s been done in the past… and the detailed mapping of projects currently underway. One important aspect is the systematic and detailed recording of ‘failed’ research paths, so that other innovators can avoid following dead-end routes. And then there are the various in-built systems for facilitating collaboration, information-exchange and networking.

It may be useful to break the Drug Discovery Challenge down into Sub-Challenges, focused on Ideation, Prototype-development, Data Analysis, etc. Or there could be a Sub-Challenge centred around virtually-testing pharmaceutical designs within specially-built modelled environments. A cleverly-gamified example of this approach is provided by ‘Foldit’, which invites innovators to design and virtually test (antibody-like) ‘protein-binders’… with the best designs offered to real-world researchers. Through various such methods, the Drug Discovery Challenge can build up an arsenal of clinical candidate pharmaceuticals… along with a diverse armoury of component technologies.

Selecting which therapies to take forward for testing can be done in a number of ways:

1. The standard Ideation Challenge process, with crowd-filtering followed by judging-panel assessment

2. Testing the innovations within modelled, virtual environments

3. Crowd-wisdom-style approach, where a specialist crowd (of 1000+ expert scientists) make individual ‘bets’ on different drug candidates – thus using a gamified ‘innovation-investment-marketplace’ to identify the therapies with the most potential

4. Rather than centralised selection, testing labs could race to pick what they think are the best candidates to take forward. Using this model would alter the dynamics of the system in a number of interesting ways

It’s probably preferable to use a mixture of these approaches – striking a fine balance between breadth and focus when deciding how many therapies go through for testing. Before entering the Mega-Trial Mainstream, these new-to-the-world pharmaceuticals need to undergo precursor evaluations for safety and relevance.

So, in the next stage, the clinical candidates are assessed in test-tubes. The testing is centrally coordinated (likely involving a network of labs) and conducted en mass. Lab teams might want to call on the crowd for assistance at certain points – for example, asking them to process data, or to provide translation services. All experimental results are openly displayed on the MMM platform.

The evaluation will highlight some drug candidates that should clearly be taken forward, although the potential of others could remain difficult to objectively assess at this stage. A ‘Results Analysis Challenge’ might help – perhaps someone’s spotted potential value, that hasn’t been recognised elsewhere.

The most-promising therapies then go through to the animal-based testing stage. Which is conducted in a similar way to the test-tube stage, funnelling treatments with the highest potential through to the human trials. (As a side-note: traditional pharmaceutical-development regulations generally require the slaughter of an unnecessarily large number of test-animals. The Coronavirus Crisis provides a good opportunity to make long-overdue reforms to the system… and the MMM platform could be the perfect place to discuss and develop such advances.)

Human testing is implemented as one massive trial, with the small and mid-sized group experiments systematically feeding into the Mega-Trial Mainstream. As always, the cogs are involved in processing and analysing the results.

Programme Features

Within the Treatment Programme, cross-cutting Challenges focus on providing foundational or enabling technologies to support core innovation efforts. For example, developing modelling software for simulating virtual environments, or useful data analysis tools. Where appropriate, support systems and technologies will be built into the Machine directly, automatically subjecting experimental results to the whole suite of applicable algorithms.

Perhaps, over the course of the Mega-Trial, one of these algorithms picks up a pattern in the data that others have missed… or a Results Analysis Challenger notices something peculiar. Maybe a drug with unimpressive results overall, actually works rather well in particular conditions (e.g. for a certain sub-section of the population, going through a specific phase of the disease). In these circumstances, the Mega-Trial would fluidly adapt to refocus treatment-testing accordingly – hopefully, leading to the development of a therapy that works in specialist cases… and a greater general understanding of C-19.

Thus, the scale and dynamics of the Machine turbo-charges our leap into the age of ‘Personalised Medicine’ proper. Open innovation, applied to MMM datasets that are both massive and granular, will uncover not only what therapies work in general (for a certain percentage of the population), but also what treatments work for specific sub-sections of the population… and ultimately which individuals. This is one example of how the Machine’s mass-production approach improves the quality, as well as quantity, of innovation outputs.

Governmental regulatory bodies should be involved in the development of Challenge success criteria and provide oversight and input throughout the innovation process. Ideally, victory conditions will be designed so that winning technologies automatically attain worldwide licensing for full-scale deployment. Closely integrating regulators into the MMM system should also facilitate the development of improved ‘Adaptive Regulations’ – flexible enough to allow innovators to tackle C-19. With the platform hosting open debates and dialogues on the subject, and utilising mechanisms such as expert-crowd-voting and virtual hackathons to assist decision-making.

All core Coronavirus treatment pharmaceuticals should be protected as public intellectual property, so anyone can manufacture them. Public IP seems natural as the Mega-Trial and Challenges are ultimately financed by global citizens. Private pharmaceutical companies have a key role to play, so the system should financially reward those who help in the development of successful therapies.

There are many ways to distribute prizes. We won’t go into the detailed economic technicalities for now, but the good news is: because the current IP regime provides such poor incentives for the most valuable innovations, it’s very possible to make improvements that genuinely work out better for everybody – i.e. win-win-win solutions for citizens, governments and private enterprise.

Treatments that achieve victory conditions can quickly go into full-scale production and distribution. Although, they don’t leave the Mega-Trial – the rollout programme is closely monitored… and even after that, it’s still useful to keep the data coming in. It’s likely we’ll need more than one therapy, so the process continues until we have a whole suite of treatments, able to reliably cover any eventuality.

It should be noted, that the MMM doesn’t seek to control and micro-manage all C-19 research. Those working within the system should enjoy maximum scientific and intellectual freedom – with the Machine tailoring itself to their needs, rather than the other way around. Of course, some innovators won’t want to fully integrate into the system, undertaking their own research projects with separate clinical trials. These researchers can pick and choose from any MMM resources they may wish to use. Perhaps they’d like to run their own programme most of the way, and then dip into the Mega-Trial for large-scale testing… or maybe they just want to utilise some specific crowdsourcing and AI mechanisms.

Researchers working outside the Treatment Challenge Programme’s main funnel could potentially participate in Challenges focused towards independent projects. With the evidence such innovators submit being assessed through the MMM, and research funds distributed towards the most promising endeavours. The system can also help innovation projects with the least potential ‘fail-fast’ (i.e. identifying scientific dead-ends, before too many resources are consumed exploring them).

Whatever happens, almost all relevant projects will, at least partially, subsume within the system – as information from their research feeds into the Machine. And, of course, all significant, externally-developed innovations will eventually be assessed through the MMM process directly.

Summary

This section has sketched the rough outline of a system for pharmaceutical development – intended as an example of how integrated crowdsourcing could be applied, rather than a definite proposal for how it should work in this specific context. There is plenty of scope for alternative models based on the same core principles and the details will ultimately need to be wrestled into reality through a painstaking, collective process of Challenge Definition.

The MMM C-19 treatment innovation procedure can be summarised as follows:

1. Refined knowledge flows into the Innovation Factory

2. Cogs develop C-19 Treatment Challenge Programme

3. Cogs identify existing drug therapies that could potentially be re-targeted at C-19

4. System assesses suggested therapies and selects most promising for experimental testing

5. System objectively tests existing drug therapies – rating, ranking and identifying success

6. Cogs generate ideas for new innovations to support treatment researchers

7. System assesses innovation ideas – highlighting most useful and filtering extraneous

8. Cogs develop prototypes of new innovations to support treatment researchers

9. System objectively tests new innovations – rating, ranking, identifying the gold-standard… and building many of these technologies into Machine itself

10. Cogs generate ideas for new drug therapies

11. System assesses suggested therapies – highlighting most useful and filtering extraneous

12. Cogs develop clinical candidate therapies

13. System assesses clinical candidate therapies and selects most promising for experimental testing

14. System conducts test-tube-based evaluation of therapies – rating, ranking and identifying candidates to take forward

15. Cogs help to process and analyse test-tube-based experimental results

16. System conducts animal-based evaluation of therapies – rating, ranking and identifying candidates to take forward

17. Cogs help to process and analyse animal-based experimental results

18. Cogs develop Mega-Trial system and sources volunteers

19. System conducts first-in-human testing with small group of healthy volunteers – rating, ranking and identifying innovations to take forward

20. Cogs help to process and analyse small-group human experimental results

21. System conducts human testing with mid-sized group of volunteers – rating, ranking and identifying innovations to take forward

22. Cogs help to process and analyse mid-sized-group human experimental results

23. System conducts human testing with large group of volunteers within the Mega-Trial Mainstream – rating, ranking and identifying success

24. Cogs help to process and analyse large group human experimental results

25. System awards prizes to treatments that fully meet victory conditions – purchasing associated IP on behalf of the world

26. System facilitates regulatory approval for treatments proven to work

27. System monitors treatments as they are deployed full-scale

28. All info, data, knowledge and innovations fed back in, assimilated and presented on the MMM platform… the process repeats, cycles and continues

29. Cogs work continuously to improve Innovation Factory – developing new systems and AI features

The MMM never sleeps as it works to bring new technologies through the research and development process. A vast conveyer belt of projects endlessly progressing through the Innovation Factory. Once the Machine is up and running, each of these steps is happening continuously – an endless pipeline of treatment ideas and technologies coming through. And, of course, a similar process should be employed to develop vaccines… for the MMM is designed to work on everything, all at once.

Read the next blog in the series - Part 6 - Action Network