Personalized, 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!