Personalised, preventive, predictive, participatory: the 4Ps of tomorrow’s medicine

The paradigm of tra­di­tion­al medi­cine, which focuses primar­ily on cur­at­ive treat­ment, is today under­go­ing rad­ic­al change, giv­ing way to a prac­tice that focuses more on pre­ven­tion than cure. In this new approach to medi­cine, the patient is no longer neces­sar­ily a per­son who is already unwell. They are con­sidered to be healthy at a giv­en moment, but poten­tially ill in the future. This art­icle aims to cla­ri­fy the real­ity of a silent revolu­tion that is for­cing us to rethink the status of what is nor­mal and what is pathological.

The word “patient” has its ori­gins in the clas­sic­al Lat­in, patiens, derived from the verb pati, “to suf­fer”. Ori­gin­ally, “patient” was used to describe a per­son suf­fer­ing from a dis­ease or dis­order of some kind that he or she was endur­ing. This defin­i­tion is no longer appro­pri­ate for the medi­cine of the future, inso­far as the future “patient” may be in good health, at least at the time of the med­ic­al exam­in­a­tion, but will still receive care to treat a poten­tial illness.

This dynam­ic con­cep­tion of a state of health (well today but ill tomor­row) marks the end of the era of tra­di­tion­al medi­cine, which was primar­ily inten­ded to be react­ive and cur­at­ive. This dynam­ic vis­ion is at the ori­gin of the concept of chron­ic dis­eases, releg­at­ing acute ill­nesses to second place since it is now rare to die from them. Today, the vast major­ity of patients are cop­ing with a long-term ill­ness (mainly car­di­ovas­cu­lar, meta­bol­ic, or men­tal and neur­o­lo­gic­al) that has a con­sid­er­able impact on their qual­ity of life.

The rise in the num­ber of cases of chron­ic dis­ease, com­bined with a bet­ter under­stand­ing of the ori­gins of patho­lo­gies, argues in favour of abandon­ing the clas­si­fic­a­tion of dis­eases as it was estab­lished towards the end of the 19th cen­tury¹. We are enter­ing a new era of medi­cine, which calls for a more glob­al and sus­tain­able approach to health. This new prac­tice is called “4P” medi­cine. It pro­motes the idea that medi­cine should not just be react­ive and cur­at­ive, but should also be pro­act­ive, inter­ven­ing well before the onset of dis­ease. The name “4Ps” aims to identi­fy the ori­gin of the semant­ic break with tra­di­tion­al prac­tice: per­son­al­ised, pre­vent­ive, pre­dict­ive and participatory.

To under­stand the advent of this new prac­tice, we first need to gain a bet­ter under­stand­ing of the his­tor­ic­al issues facing tra­di­tion­al medi­cine, and then con­sider the spe­cif­ic fea­tures of the glob­al approach to health offered by 4P medi­cine. Finally, it is import­ant to exam­ine the eth­ic­al chal­lenges we will face when this concept is developed on a large scale.

The term 4Ps medi­cine was ori­gin­ally coined to sig­ni­fy the emer­gence of a new way of prac­tising medi­cine². This approach pro­poses a new thera­peut­ic frame­work that aims to treat not only the symp­toms, but also the under­ly­ing causes of dis­ease, with great­er emphas­is on pre­ven­tion and pro­mot­ing over­all bal­ance. It is for this reas­on that the World Health Organ­isa­tion (WHO) defines health as “a state of com­plete phys­ic­al, men­tal, and social well-being and not merely the absence of dis­ease or infirmity.”

In order to under­stand this new defin­i­tion of health, 4P medi­cine is first of all described as per­son­al­ised, because unlike con­tem­por­ary medi­cine, which is prac­tised on the scale of a gen­er­al pop­u­la­tion³, 4P medi­cine takes account of an individual’s spe­cif­ic char­ac­ter­ist­ics, such as his or her genet­ic and epi­gen­et­ic pro­file, by using the cloud of data con­cern­ing him or her. It is then pos­sible to assess the genet­ic and envir­on­ment­al con­tri­bu­tion to their health. In the United States, the dose admin­istered for cer­tain anti­co­agu­lant treat­ments is now determ­ined once the subject’s genet­ic pro­file has been estab­lished. This focus on the indi­vidu­al offers prom­ising advant­ages when it comes to design­ing clin­ic­al tri­als for drugs, because it is unreal­ist­ic to assume that all indi­vidu­als react in the same way to a treatment.

Every can­cer and every tumour has genet­ic and bio­chem­ic­al dif­fer­ences that can be used to design pre­ci­sion medicines.

This new med­ic­al prac­tice is also pre­vent­ive, as it con­siders the state of well-being before ill­ness. To achieve this, it relies on the digit­al revolu­tion, which enables the col­lec­tion of data on a massive scale⁴, epi­demi­olo­gic­al sur­veil­lance and the per­son­al­isa­tion of health recom­mend­a­tions accord­ing to patients’ indi­vidu­al char­ac­ter­ist­ics. It is also pre­dict­ive, since it allows us to con­sider the most appro­pri­ate treat­ment for a patient, max­im­ising its effect­ive­ness. As with per­son­al­isa­tion, pre­cise know­ledge of the patient also makes it pos­sible to anti­cip­ate pos­sible side effects. Finally, unlike tra­di­tion­al medi­cine, which mainly uses the health pro­fes­sion­al and pub­lic ser­vices to provide health edu­ca­tion, 4P medi­cine places net­works (pub­lic, patient and health pro­fes­sion­al) at its heart to inform and edu­cate patients, health pro­fes­sion­als, carers and fam­ily and friends. It is for this reas­on that it is described as par­ti­cip­at­ory since it invites the sub­ject to become a play­er in their own care pro­gramme⁵.

The advent of this type of medi­cine is due to the con­ver­gence of five new paradigms. The first was the devel­op­ment and demo­crat­isa­tion of tools for ana­lys­ing the mech­an­isms of liv­ing organ­isms. This step was the res­ult of the birth of molecu­lar bio­logy, marked by the award of the Nobel Prize for Medi­cine to three French research­ers, André Lwoff, Jacques Monod and François Jac­ob, the founders of this new dis­cip­line⁶, which ini­tially made it pos­sible to devel­op gene clon­ing, and then to lay the tech­no­lo­gic­al found­a­tions for bio­tech­no­lo­gies. The second paradigm was the imple­ment­a­tion of major fed­er­at­ive and transna­tion­al pro­jects, which led in par­tic­u­lar to the sequen­cing of the human gen­ome. For the first time, it became pos­sible to cor­rel­ate genet­ic vari­ants with phen­o­types⁷. The third paradigm is based on the cre­ation of mul­tidiscip­lin­ary med­ic­al and sci­entif­ic teams, bring­ing togeth­er doc­tors, bio­lo­gists, chem­ists, engin­eers, com­puter sci­ent­ists and oth­ers. This need for inter­dis­cip­lin­ar­ity poses a real chal­lenge to cur­rent teach­ing pro­grammes in bio­med­ic­al sci­ence uni­ver­sity courses. Next, the fourth was the devel­op­ment of a new dis­cip­line, sys­tems bio­logy. Sys­tems bio­logy is a more glob­al and integ­rat­ive study of the rules of liv­ing sys­tems. It dif­fers from the old reduc­tion­ist strategy, which con­sisted of under­stand­ing bio­logy at its simplest level, gene by gene, then pro­tein by pro­tein, and so on. The final paradigm shift was the con­cep­tu­al­isa­tion of a new med­ic­al prac­tice known as sys­tems medi­cine, the res­ult of apply­ing sys­tems bio­logy to med­ic­al practice.

In per­son­al­ised medi­cine, care and treat­ment are geared towards the indi­vidu­al. The aim is to select the most appro­pri­ate treatment(s) based on the individual’s genet­ic, phen­o­typ­ic and life­style char­ac­ter­ist­ics. Per­son­al­ised medi­cine is now a real­ity in onco­logy, and 70% of the com­pounds developed in this field are so-called pre­ci­sion medi­cines. This makes par­tic­u­lar sense now that know­ledge and under­stand­ing of can­cer mech­an­isms have improved. Every can­cer and every tumour has genet­ic and bio­chem­ic­al dif­fer­ences that can be used to design pre­ci­sion medicines.

The medi­cine of the future will leave a large part to the involve­ment and act­ive par­ti­cip­a­tion of the patient in the treat­ment, mak­ing it more effect­ive. The aim of this type of medi­cine is to facil­it­ate cooper­a­tion between doc­tors and patients through a bet­ter under­stand­ing of their patho­logy and its impact on their daily lives, and to sig­ni­fic­antly improve their life expect­ancy and qual­ity of life. In prac­tice, this col­lab­or­at­ive dimen­sion is trans­form­ing the patient from a pass­ive par­ti­cipant to a cent­ral play­er in the care process.

To facil­it­ate this trans­ition, the “Kouch­ner Law” marked a major turn­ing point by promoting:

1. Patients’ free and informed con­sent to the pro­ced­ures and treat­ments pro­posed to them
2. Patient’ right to be informed about their state of health.

But the law was not the only cata­lyst for this trans­form­a­tion. The tech­no­lo­gic­al pos­sib­il­it­ies for imple­ment­ing par­ti­cip­at­ory medi­cine are infin­ite. These include mobile applic­a­tions for man­aging patho­lo­gies and/or treat­ments, con­nec­ted objects, com­mu­nic­a­tion tools between patients and health­care pro­fes­sion­als, e‑prescription, and the pos­sib­il­ity of con­sult­ing the res­ults and reports of vari­ous ana­lyses and treat­ment pro­ced­ures online.

This irre­vers­ible evol­u­tion of medi­cine is a major chal­lenge for the 21st cen­tury and its future generations

Finally, it should be emphas­ised that the use of per­son­al­ised medi­cine offers an oppor­tun­ity to renew bio­med­ic­al research. Patients can be called on to take part in research pro­grammes that go bey­ond the tra­di­tion­al clin­ic­al tri­als for new drugs. To make the pro­cess of devel­op­ing new drugs short­er and cheap­er, the All of us research pro­gramme, for example, run in the USA by the Nation­al Insti­tutes of Health, aims to col­lect data from at least one mil­lion people liv­ing in the United States. The aim is to provide research­ers with per­son­al data to study the pro­spects offered by pre­ci­sion medi­cine, by examin­ing the exist­ing dif­fer­ences between the life­style, envir­on­ment and bio­lo­gic­al char­ac­ter­ist­ics of each indi­vidu­al. Based on envir­on­ment­al expos­ure, genet­ic factors and the inter­ac­tion between these two ele­ments, it will be pos­sible to assess the risk of con­tract­ing a num­ber of dis­eases, to determ­ine the causes of the dif­fer­ences that exist from one per­son to anoth­er in terms of the effects pro­duced by com­monly used drugs, to identi­fy bio­lo­gic­al mark­ers asso­ci­ated with an increased or reduced risk of devel­op­ing cer­tain com­mon dis­eases, to estab­lish new clas­si­fic­a­tions of dis­eases and new links between them, to com­mu­nic­ate data and inform­a­tion to study par­ti­cipants to give them the means to improve their state of health, and finally to cre­ate a plat­form designed to enable tar­geted ther­apy tri­als to be car­ried out.

Sim­il­ar pro­grammes exist in France, such as the pub­lic Com­PaRe pro­gramme (Com­munity of Patients for Research)⁸ pro­posed by the APHP (Assist­ance pub­lique des hôpitaux de Par­is) in col­lab­or­a­tion with Uni­versité Par­is-Cité. It is based on an e‑cohort of adult patients suf­fer­ing from chron­ic ill­nesses, who will give up some of their time to reg­u­larly answer online ques­tion­naires on the state of their ill­nesses and treat­ments, using a col­lab­or­at­ive plat­form. The aim is to be able to use the data col­lec­ted to answer research ques­tions on chron­ic dis­eases. This is achieved through a com­munity of patients who can get involved in the design, imple­ment­a­tion, and ana­lys­is of research pro­jects. So, as with pre­vent­ive, pre­dict­ive, and per­son­al­ised medi­cine, this col­lab­or­at­ive dimen­sion is based on the gen­er­a­tion, stor­age and ana­lys­is of mul­ti­di­men­sion­al data to improve qual­ity of life, optim­ise care path­ways and guar­an­tee the well-being of pop­u­la­tions. This trend shows that it is pos­sible to take an interest in both the indi­vidu­al and the col­lect­ive, without hav­ing to over­come para­dox­ic­al injunctions.

Des­pite the undeni­able advant­ages offered by this new med­ic­al prac­tice, it poses sev­er­al chal­lenges that need to be over­come before we can fully bene­fit from its pos­it­ive effects.

#1 Technical challenges

In any clin­ic­al study, only a frac­tion of the bio­lo­gic­al vari­ab­il­ity is cap­tured (and there­fore ana­lysed) because of tech­nic­al lim­it­a­tions (data har­mon­isa­tion, data het­ero­gen­eity), the exper­i­ment­al tools avail­able and the cost involved. The devel­op­ment of exper­i­ment­al tools will cer­tainly gen­er­ate new inform­a­tion, but at the same time, massive quant­it­ies of data will have to be prop­erly pro­cessed, ana­lysed and inter­preted. This poses a num­ber of tech­no­lo­gic­al chal­lenges in terms of the mean­ing of the data col­lec­ted, which could be resolved using gen­er­at­ive arti­fi­cial intel­li­gence. Machine learn­ing tech­niques for learn­ing and gen­er­al­ising from data, as well as advanced stat­ist­ic­al tech­niques, will play an import­ant role in ana­lys­ing all the mul­ti­di­men­sion­al data gen­er­ated by tomorrow’s med­ic­al tech­no­lo­gies. Unfor­tu­nately, neither France nor Europe can cur­rently guar­an­tee the sov­er­eignty of these analyses.

What’s more, it’s clear that IT tools alone will not be enough to meet the chal­lenge of deci­pher­ing the com­plex­ity of liv­ing organ­isms. Expert­ise in the field of bio­logy is essen­tial, as dec­ades of research can be put to good use in help­ing to inter­pret the data that is begin­ning to accu­mu­late. Without a deep and grow­ing under­stand­ing of liv­ing phe­nom­ena, it will not be pos­sible to find crit­ic­al sig­nals amid the vast quant­it­ies of data col­lec­ted in het­ero­gen­eous data­bases. Find­ing the weak sig­nals in the din of back­ground noise remains a major tech­nic­al chal­lenge for 4P medicine.

#2 Challenges for healthcare systems

The steps needed to make this new med­ic­al prac­tice a real­ity go far bey­ond simple techno-sci­entif­ic advances. The entire struc­ture of the health­care sys­tem needs to be rethought to work with mul­tidiscip­lin­ary teams made up of doc­tors, epi­demi­olo­gists, bio­lo­gists, com­puter sci­ent­ists and stat­ist­i­cians, and enriched by new expert­ise (genet­ic coun­sel­lors, beha­vi­our­al coaches, spe­cial­ised edu­cat­ors, etc.).

What’s more, most chron­ic dis­eases require com­plex man­age­ment involving dozens of dif­fer­ent parties: health­care pro­fes­sion­als, para­med­ic­al staff, social care pro­fes­sion­als and so on. How­ever, with the hyper-spe­cial­isa­tion of pro­fes­sions, the num­ber of play­ers increases ten­fold and the patient’s path­way becomes increas­ingly chaot­ic. The need for coordin­a­tion and shar­ing of patient data between all these vari­ous pro­fes­sion­als is vital to the suc­cess of patient care⁹.

As far as patients are con­cerned, although half want to let their doc­tor tell them what is best for them, the oth­er half want to receive care from this new prac­tice. It will be vital to ensure that the adop­tion and demo­crat­isa­tion of this medi­cine of the future does not pro­duce more health inequal­it­ies than already exist. To this end, it is advis­able to con­sider 4P medi­cine edu­ca­tion pro­grammes to ensure that cit­izens are aware of this prac­tice and can bene­fit from it. Finally, the eco­nom­ic cost of this new med­ic­al prac­tice should not be a bar­ri­er to patients, and innov­at­ive busi­ness mod­els should be devised accordingly.

#3 Ethical data challenges

Respect for patient pri­vacy remains one of the main obstacles to the imple­ment­a­tion of a new 4P medi­cine. Trust in a medi­cine based on the use of digit­al tech­no­logy to gen­er­ate, col­lect, store, and ana­lyse private data is intim­ately linked to the issue of con­fid­en­ti­al­ity, integ­rity, respons­ib­il­ity, authen­ti­city and secure data man­age­ment. The chal­lenges posed by cyber­crime and the secur­ity of per­son­al data are major stakes in the suc­cess­ful demo­crat­isa­tion of 4P medicine.

It is only by over­com­ing all these chal­lenges that 4P medi­cine will be able to offer a new way of dia­gnos­ing, treat­ing and pre­vent­ing dis­ease, by provid­ing more pre­cise and effect­ive care, tailored to the indi­vidu­al needs of each person.

The 20th cen­tury saw major med­ic­al innov­a­tions such as anti­bi­ot­ics, vac­cines, anaes­thesia, chemo­ther­apy and, more recently, the emer­gence of evid­ence-based medi­cine (based on the best sci­entif­ic evid­ence), min­im­ally invas­ive sur­gery (lap­aro­scopy), out­pa­tient sur­gery and enhanced rehab­il­it­a­tion. At the dawn of the 21st cen­tury, anoth­er more glob­al devel­op­ment is under­way to pro­mote medi­cine that is adap­ted to each individual’s know­ledge of their genes, com­bined with their life­style. The aim of this art­icle is to give a brief over­view of the found­a­tions, to pre­pare us for this revolu­tion and these new chal­lenges, so that we can pro­mote the uni­ver­sal, non-mer­cant­ile applic­a­tion of advances in med­ic­al science.

It is clear that 4P medi­cine offers a much more glob­al vis­ion of per­son­al­ised medi­cine, and that it is destined to trans­form the man­age­ment of our health, our patho­lo­gies and our med­ic­al prac­tices. For this medi­cine of the future, med­ic­al con­sulta­tions will be motiv­ated less by symp­toms than by cal­cu­lat­ing the prob­ab­il­ity of suf­fer­ing from a dis­ease. Of course, this raises a num­ber of ques­tions that invite us to rethink the doc­tor-patient rela­tion­ship and the future role of gen­er­al prac­ti­tion­ers. How can future doc­tors be trained in this approach? This medi­cine of the future emphas­ises the par­ti­cip­a­tion of indi­vidu­als, but this aspect is appre­ci­ated dif­fer­ently by the par­ti­cipants. It’s not just a ques­tion of tak­ing account of people’s choices and val­ues in the shared med­ic­al decision, it’s also a ques­tion of involving people in mon­it­or­ing cer­tain indic­at­ors (organ­ic or bio­lo­gic­al) through optim­al thera­peut­ic edu­ca­tion tailored to each indi­vidu­al, depend­ing on their socio-eco­nom­ic con­text. In oth­er words, if patients become “experts” in the future, will we all be equal and pre­pared for this trans­form­a­tion? How can this move­ment be inclusive?

Search­ing for risk factors and announ­cing them years before the pos­sible onset of the dis­ease entails obvi­ous risks of dis­crim­in­a­tion in recruit­ment or in obtain­ing loans or insur­ance (revised pri­cing accord­ing to risk). This is a major prob­lem inso­far as 4P medi­cine aims to cat­egor­ise patients as “sick”, “at risk”, “not sick” or “cured”. Are we head­ing for a med­ic­al archipel­it­isa­tion of soci­ety? What’s more, group­ing indi­vidu­als into strata accord­ing to their med­ic­al risks car­ries the danger of see­ing a return to “racial­ized” medi­cine, when we know that the somat­ic expres­sion of genet­ic par­tic­u­lar­it­ies is not con­stant, and that epi­gen­et­ics comes into play to vary­ing degrees¹⁰. Finally, since the medi­cine of the future will provide us with know­ledge about our future and our risk of devel­op­ing patho­lo­gies, there is a great risk that the com­munity will become dis­united¹¹.

The chal­lenge for health­care in the years to come will be to take account of each individual’s unique­ness, but also to ensure that each indi­vidu­al is under­stood as a whole. Will 4P medi­cine mean that pre­vent­ive meas­ures and pre­scrip­tions will hence­forth be guided by know­ledge of our DNA com­bined with know­ledge of our life­style? If anti­cip­at­ing the import­ance of 4P medi­cine in the trans­form­a­tion of health and medi­cine is no longer an option, let us remain com­mit­ted to this excit­ing jour­ney towards a future that brings us togeth­er rather than divides us. This irre­vers­ible evol­u­tion of medi­cine is a major chal­lenge for the 21st cen­tury and its future gen­er­a­tions. Let’s not miss this oppor­tun­ity to build a world that is both fairer and more united!