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T*
[(co)19.7(mp)19.6(le)19.5(me)18.4(nt)15(ar)19.7(y,)-666.9(an)19.7(d)-675(i)0(n)20.7(t)0(e)13.8(g)0(r)20.9(a)0(t)19.5(i)0(v)20.7(e)-681.9(m)15(e)0(d)13.9(i)0(c)19.6(i)0(n)20.7(e)-676.1(\(T)19.7(CI)14.1(M\))20(h)19.7(av)19.7(e)]TJ
0 -1.1174 TD
[(cr)19.7(it)20.6(iq)15(ue)19.7(d)-346.7(t)0(h)20.7(e)-353.6(RC)18.8(T)19.7(s)-352.2(l)0(i)20.6(m)0(i)19.5(t)0(a)19.6(t)0(i)20.6(o)0(n)20.8(s)-352.2(an)19.7(d)-352.4(i)0(t)20.6(s)-346.5(di)14.9(sp)21(ro)20.9(po)20.8(rt)15(io)20.7(na)19.7(te)-337.5(ev)13.9(i-)]TJ
0 -1.1116 TD
[(de)19.7(nt)20.7(ia)13.8(ry)-480.2(do)20.8(mi)19.5(na)19.7(nc)19.7(e.)-483.7(Th)19.6(e)-491.8(p)0(r)20.9(e)0(s)14.1(e)0(n)19.7(t)-490.8(wo)20(rk)20.9(,)-493(a)-491.8(sc)19.9(op)20.8(in)15(g)-490.7(r)0(e)19.7(v)0(i)20.7(e)0(w)18.8(,)]TJ
T*
[(re)19.7(pr)15.1(es)19.9(en)19.7(ts)-249.8(a)-261.4()0(r)21(s)0(t)-249.8(r)0(e)19.7(t)0(r)20.7(o)0(s)15.3(p)0(e)19.7(c)0(t)19.5(i)0(v)20.7(e)-261.4(an)19.7(al)19.5(ys)21(is)-249.8(of)-249.8(al)19.5(mo)19.6(st)-249.8(tw)14.1(o)-254.5(d)0(e)19.7(c)0(a)12.8(d)0(e)19.7(s)]TJ
0 -1.1174 TD
[(of)-324.7(re)19.7(se)14.1(ar)19.7(ch)-325.9(de)19.7(si)20.9(gn)-324.7(ad)19.7(va)19.7(nc)13.9(es)-325.7(ma)18.4(de)-325.9(by)-324.7(sc)19.9(ho)20.8(la)19.6(rs)-324.5(co)13.9(m)15(m)0(i)19.5(t)0(t)14.8(e)0(d)-325.9(t)0(o)]TJ
0 -1.1116 TD
[(ri)20.7(go)15.1(ro)20.9(us)21(,)-544.8(h)0(o)20.8(l)0(i)20.6(s)0(t)20.9(i)0(c)-539.1(c)0(l)19.5(i)0(n)20.7(i)0(c)19.6(a)0(l)-533.4(r)0(e)19.7(s)0(e)14.1(a)0(r)19.7(c)0(h)-533.3(d)0(e)19.7(s)0(i)20.9(g)0(n)15.1(s)-542.3(th)20.7(at)-533.4(ac)18.5(cu)19.7(ra)14(te)19.6(ly)]TJ
T*
[(re)19.7(pr)15.1(es)19.9(en)19.7(t)-323.8(t)0(h)20.7(e)-324.8(un)20.8(iq)20.7(ue)-314.4(pa)19.7(ra)19.7(di)20.7(gm)19.6(at)13.8(ic)-314.5(fe)19.7(at)19.5(ur)20.9(es)-314.2(of)-313.2(TC)18.6(IM)-314.1()62.3()0(w)14.2(h)0(o)20.8(l)0(e)]TJ
0 -1.1174 TD
[(sy)21(st)15.1(em)18.5(s)72.9()-323.6(i)0(n)20.7(t)0(e)19.5(r)0(v)15.1(e)0(n)19.7(t)0(i)20.6(o)0(n)20.8(s)0(.)]TJ
/F14 1 Tf
8.9663 0 0 8.9663 62.022 336.0188 Tm
(Background)Tj
/F6 1 Tf
9.843 0 0 9.843 72 319.5779 Tm
[(In)-589.7(20)20.8(03)20.8(,)-596.7(R)0(i)19.7(t)0(e)13.8(n)0(b)20.8(a)0(u)19.7(g)0(h)-589.7(e)0(t)-591(a)0(l)19.5(.)13.9(r)19.8(es)14.1(ea)18.5(rc)19.7(he)19.7(rs)-589.5(in)-589.8(th)20.7(e)-601.3(T)0(C)18.6(I)0(M)]TJ
-1.0137 -1.1116 TD
[(e)19.8(ld)20.7(p)19.7(ub)15.1(li)20.6(sh)21(ed)-274.1(a)-278.7(s)0(e)14.1(m)0(i)19.5(n)0(a)19.7(l)-283.5(ar)19.7(ti)20.6(cl)19.5(e)-284.5(p)0(r)20.9(o)0(p)20.8(o)0(s)21(i)0(n)15(g)-277.6(a)-284.5(n)0(e)19.7(w)-284.2(br)20.9(an)19.7(ch)-274.1(of)]TJ
T*
[(sc)19.9(ie)19.5(nt)15(i)20.9(c)-514.9(i)0(n)20.7(q)0(u)15.1(i)0(r)20.7(y)0(,)-505.6(w)0(h)20(i)0(c)19.6(h)-519.5(th)20.7(ey)-504.5(te)13.8(rm)19.6(ed)-504.5()56.5()0(w)20(h)0(o)20.8(l)0(e)-504.6(s)0(y)15.3(s)0(t)20.9(e)0(m)18.5(s)-519.3(re)19.7(-)]TJ
0 -1.1174 TD
[(se)19.9(ar)14(ch)19.7()62.3()-237.2(\(W)18.6(SR)20(\).)]TJ
7.3823 0 0 6.5614 124.7244 291.0613 Tm
(5)Tj
9.843 0 0 9.843 130.7338 286.696 Tm
-.0202 Tc
[(W)-20.2(S)-1.5(R)-258.5(p)-20.2(io)-20.2(ne)-20.2(er)-20.2(s)-246.8(p)-20.2(r)-5.1(o)-20.2(po)-20.2(se)-20.2(d)-248.2(t)-20.2(o)-247.2(i)-20.2(nn)-20.2(ov)-20.2(at)-20.2(e)-248.3(c)-20.2(li)-20.2(n)-5.2(i)-20.2(ca)-20.2(l)]TJ
-6.9808 -1.1116 TD
0 Tc
[(re)19.7(se)14.1(ar)19.7(ch)-504.5(de)19.7(si)20.9(gn)20.8(s)-519.3(t)0(o)-503.4(a)0(d)19.7(d)0(r)20.9(e)0(s)19.9(s)-519.3(th)20.7(e)-514.9(t)0(h)20.7(e)0(o)19.7(r)0(e)19.7(t)0(i)14.8(c)0(a)18.5(l)0(-)20.7(m)0(e)18.4(t)0(h)20.7(o)0(d)20.8(o)0(l)20.7(o)0(g)15.1(i)0(c)19.6(a)0(l)]TJ
T*
[(di)20.7(ss)15.5(on)20.8(an)19.7(ce)-350.1(th)20.7(at)-349.1(ma)18.4(y)-358.2(a)0(r)19.7(i)0(s)20.9(e)-359.4(in)-347.9(us)21(in)20.7(g)-358.2(c)0(l)19.5(a)0(s)19.9(s)0(i)15.1(c)0(a)18.5(l)-352.6(RC)18.8(T)-359.4(d)0(e)19.7(s)0(i)15.1(g)0(n)20.8(s)0()]TJ
0 -1.1174 TD
[(re)19.7(ve)19.7(re)14(d)-404.3(a)0(s)-400.6(t)0(h)20.7(e)-411.2()56.5()0(g)20.9(o)0(l)20.7(d)-410(st)20.9(an)19.7(da)19.7(rd)15.1()62.3()-410(in)-399.7(bi)20.7(om)19.6(ed)19.7(ic)19.6(al)-400.9(re)19.7(se)19.9(ar)14(ch)19.7(t)19.6(o)]TJ
0 -1.1116 TD
[(ap)19.7(pr)20.9(op)15.1(ri)20.7(at)19.5(el)19.5(y)-565.5(s)0(t)15.1(u)0(d)20.8(y)-565.5(TC)18.6(IM)-556(ca)18.5(re)19.7(.)-567.9(T)0(C)18.6(I)0(M)-556()62.3(w)20(ho)15.1(le)-556.4(sy)21(st)20.9(em)18.5(s)67.1()]TJ
T*
[(pa)19.7(ra)19.7(di)14.9(gm)19.6(s)-461.7(\()0(e)19.7(.)0(g)18.5(.)0(,)-450.4(C)0(h)14(i)0(n)20.7(e)0(s)19.9(e)-463(me)18.4(di)20.7(ci)13.8(ne)-452.6(an)19.7(d)-461.9(n)0(a)19.7(t)0(u)15(r)0(o)20.9(p)0(a)19.7(t)0(h)20.7(i)0(c)-458.5(m)15(ed)13.9(i-)]TJ
0 -1.1174 TD
[(ci)19.5(ne)19.7(\),)-465.3(th)20.7(ey)-464.1(ar)19.7(gu)15.1(ed)19.7(,)-470(e)0(x)19.7(e)0(m)18.5(p)0(l)15(i)0(f)20.7(y)-473.4(se)19.9(ve)19.7(ra)19.7(l)-473.5(c)0(e)18.5(n)0(t)14.9(r)0(a)19.7(l)-473.5(fe)19.7(at)19.6(ur)20.9(es)-463.9(\(d)15.1(e-)]TJ
0 -1.1116 TD
[(ta)19.5(il)20.6(ed)-763.6(be)19.7(lo)20.7(w\))-763.3(th)20.7(at)-758(di)15(st)20.9(in)20.7(gu)20.8(is)20.9(h)-772.9(t)0(h)20.7(e)0(m)-759.1(f)0(r)15.1(o)0(m)-757.9(c)0(o)19.7(n)0(v)20.8(e)0(n)19.7(t)0(i)14.8(o)0(n)20.8(a)0(l)]TJ
T*
[(bi)20.7(om)19.6(ed)19.7(ic)13.8(in)20.7(e.)-512.5(At)-515.8(th)20.7(e)-520.6(h)0(e)19.7(a)0(r)19.7(t)-525.4(of)-514.8(WS)18.7(R)-520.5(i)0(s)-514.7(t)0(h)20.7(e)-520.6(mo)19.6(de)13.9(l)-519.6(v)0(a)19.7(l)0(i)20.6(d)0(i)14.9(t)0(y)]TJ
0 -1.1174 TD
[(pr)20.9(in)15(ci)19.5(pl)20.7(e,)-299.4(de)19.7(n)21(ed)-302.9(he)19.7(re)-302.8(as)-302.7(th)20.7(e)-313.3()62.3()21(t)66.8()-306.3(b)0(e)19.7(t)0(w)14.1(e)0(e)18.5(n)-306.4(a)-313.3(s)0(t)20.9(u)0(d)20.8(y)0()15.1(s)-306.2(de)19.7(si)15.1(gn)]TJ
0 -1.1116 TD
[(an)19.7(d)-329.4(t)0(h)20.7(e)-330.6(co)19.7(nc)19.7(ep)13.9(tu)20.7(al)-320.3(an)19.7(d)-329.4(c)0(l)19.5(i)0(n)20.7(i)0(c)19.6(a)0(l)-320.3(f)0(e)19.7(a)0(t)19.5(u)0(r)15.1(e)0(s)-320(o)0(f)-318.9(t)0(h)20.7(e)-330.6(st)20.9(ud)20.8(ie)19.6(d)-329.4(i)0(n)20.7(t)0(e)13.8(r)0(-)]TJ
T*
[(ve)19.7(nt)20.7(io)15(n)20.9(s)-421.4(u)0(n)20.8(d)0(e)13.9(r)0(l)20.7(y)0(i)20.7(n)0(g)-411.1(o)0(r)-416.9(o)0(r)20.9(i)0(g)20.7(i)0(n)15(a)0(t)19.5(i)0(n)20.7(g)-421.6(pa)19.7(ra)14(di)20.7(gm)19.6(.)]TJ
7.3823 0 0 6.5614 245.8771 170.5323 Tm
(6)Tj
9.843 0 0 9.843 253.7574 166.1669 Tm
[(WS)18.7(R)-422.6(a)0(d)13.9(v)0(o)20.8(-)]TJ
-19.4793 -1.1116 TD
[(ca)18.5(te)19.6(s)-415.6(e)0(n)19.7(v)0(i)14.9(s)0(i)20.9(o)0(n)20.8(e)0(d)-406.5(t)0(h)20.7(e)-417(pu)20.8(rs)21.1(ui)14.9(t)-410.2(o)0(f)-405.3(m)0(o)19.6(d)0(e)13.9(l)-410.2(va)13.9(li)20.6(di)20.7(ty)-405.5(as)-406.3(a)-417(w)0(a)18.8(y)-415.8(to)]TJ
0 -1.1174 TD
[(ri)20.7(go)15.1(ro)20.9(us)21(ly)-342.1(su)15.3(pp)20.8(le)19.6(me)18.4(nt)-342.2(\(a)19.7(nd)-347.8(re)19.7(pr)20.9(io)20.7(ri)15(ti)20.6(ze)18.5(\))-352.4(e)0(x)19.7(i)0(s)15.2(t)0(i)20.6(n)0(g)-342(a)0(p)19.7(p)0(r)20.9(o)0(a)19.7(c)0(h)13.9(e)0(s)]TJ
0 -1.1116 TD
[(to)-227(ac)18.5(hi)14.9(ev)19.7(in)20.7(g)-237.2(e)0(x)19.7(t)0(e)19.5(r)0(n)15.1(a)0(l)-228.1(a)0(n)19.7(d)-237.2(in)20.7(te)19.6(rn)15.1(al)-228.1(va)19.7(li)20.6(di)20.7(ty)-232.7(in)-227(cl)19.5(in)20.7(ic)19.6(al)-228.1(re)14(se)19.9(ar)19.7(ch)19.7(.)]TJ
1.0137 -1.1116 TD
[(Th)19.6(e)-238.4(d)0(o)20.8(m)0(i)19.5(n)0(a)19.7(n)0(t)-227(R)0(C)18.8(T)-238.4(de)19.7(si)20.9(gn)20.8(,)-239.6(a)0(s)-227.8(c)0(r)19.7(i)0(t)20.6(i)0(c)19.6(s)-237(ha)19.7(d)-237.2(o)0(b)20.8(s)0(e)19.9(r)0(v)15.1(e)0(d)-228(o)0(v)20.8(e)0(r)-228(t)0(h)20.7(e)]TJ
-1.0137 -1.1174 TD
[(tw)19.8(o)-335.2(d)0(e)19.7(c)0(a)18.5(d)0(e)19.7(s)-335(pr)15.1(io)20.7(r,)]TJ
7.3823 0 0 6.5614 134.9291 115.7102 Tm
-.0162 Tc
[(7)-16.2(9)]TJ
9.843 0 0 9.843 149.1023 111.3448 Tm
0 Tc
[(se)19.9(ek)19.7(s)-335(t)0(o)-324.9(s)0(t)20.9(u)0(d)15.1(y)-329.4(si)15.1(ng)20.8(ul)20.7(ar)19.7(,)-337.5(i)0(s)20.9(o)0(l)20.7(a)0(t)19.5(e)0(d)-325.9(t)0(h)20.7(e)0(r)14(a)0(-)]TJ
-8.8469 -1.1116 TD
[(pe)19.7(ut)20.7(ic)-222.4(co)19.7(mp)19.6(on)20.8(en)19.7(ts)-215.2(to)-221.2()62.3()0(d)20.9(e)0(t)19.5(e)0(r)19.7(m)0(i)19.5(n)0(e)-222.2(t)0(h)20.7(e)-226.9(si)20.9(ng)20.8(le)-216.6(be)13.9(st)-215.2(tr)20.7(ea)18.5(tm)19.5(en)19.7(t)-225.9(f)0(o)15.1(r)]TJ
T*
-.0188 Tc
[(a)-18.8(l).7(l)-296.5(p)-18.8(at)-18.8(ie)-18.8(nt)-18.8(s.)-4.9()37.7()]TJ
7.3823 0 0 6.5614 112.7055 93.8268 Tm
0 Tc
(5)Tj
9.843 0 0 9.843 119.1118 89.4614 Tm
[(TC)18.6(IM)-262.3(tr)20.7(ea)12.8(tm)19.5(en)19.7(ts)20.9(,)-274.1(h)0(o)20.8(w)0(e)18.8(v)0(e)13.9(r)0(,)-263.7(a)0(r)19.7(e)-273(ty)15(pi)20.7(ca)18.5(ll)20.6(y)-277.6(c)0(o)19.7(m)0(-)]TJ
-5.8 -1.1174 TD
[(pl)20.7(ex)-383.5(\(i)20.7(nv)20.8(ol)20.7(vi)20.7(ng)-382.3(mu)19.6(lt)20.6(ip)20.7(le)-383.6(sy)21(ne)19.7(rg)20.9(is)20.9(ti)14.8(c)-388.2(t)0(r)20.7(e)0(a)18.5(t)0(m)19.5(e)0(n)19.7(t)-392.9(mo)19.6(da)19.7(li)20.6(ti)20.6(es)-383.3(or)]TJ
0 -1.1116 TD
[(co)19.7(mp)19.6(on)20.8(en)13.9(ts)20.9(\))-173.9(a)0(n)19.7(d)-173.9(in)15(di)20.7(vi)20.7(du)20.8(al)19.5(ly)-169.4(ta)19.6(il)20.6(or)20.9(ed)-164.6(to)-169.4(th)20.7(e)-175(s)0(p)21(e)0(c)18.5(i)0()15.1(c)-175(pa)19.7(ti)20.6(en)19.7(t.)]TJ
7.3823 0 0 6.5614 292.0818 71.8866 Tm
[(6,)28.1(9)]TJ
9.843 0 0 9.843 62.022 56.5795 Tm
[(Cl)19.7(as)19.9(si)15.1(ca)18.5(l)-318(R)0(C)18.8(T)0(s)-308.5(w)0(e)18.8(r)0(e)-308.6(p)0(u)20.8(r)0(p)15.1(o)0(s)21(e)-319(de)19.7(ve)19.7(lo)20.7(pe)19.7(d)-317.9(t)0(o)-307.6(a)0(s)14.1(s)0(e)19.9(s)0(s)-307.1(t)0(h)20.7(e)-319(ca)18.5(us)15.3(al)]TJ
25.504 62.3546 TD
-.0201 Tc
[(e)-20.1(f)-6.1(f)-20.1(e)-.4(c)-20.1(t)-.6(s)-372.3(o)-20.1(f)-362.1(p)-20.1(ha)-20.1(rm)-20.1(ac)-20.1(e)-7.3(u)-20.1(ti)-20.1(c)-363.4(t)-20.1(re)-20.1(at)-20.1(me)-20.1(nt)-20.1(s)-362.1(o)-20.1(n)-362.1(p)-20.1(a)-6.2(r)-20.1(ti)-20.1(cu)-20.1(la)-20.1(r)-363.3(p)-20.1(hy)-20.1(s)-4.8(i)-20.1(ol)-20.1(og)-20.1(ic)]TJ
0 -1.1116 TD
0 Tc
[(pa)13.9(th)20.7(wa)18.8(ys)21(,)-510.3(u)0(n)20.8(d)0(e)19.7(r)-513.7(do)20.8(ub)20.8(le)19.5(-b)15.1(li)20.6(nd)20.8(ed)19.7(,)-510.3(p)0(l)20.7(a)0(c)18.5(e)0(b)19.7(o)0(-)15.1(c)0(o)19.7(n)0(t)20.7(r)0(o)20.9(l)0(l)20.6(e)0(d)-504.5(c)0(o)19.7(n)0(d)20.8(i)0(-)]TJ
0 -1.1174 TD
[(ti)14.8(on)20.8(s.)]TJ
7.3823 0 0 6.5614 334.1479 652.8187 Tm
-.0173 Tc
[(10)-17.3(,11)]TJ
9.843 0 0 9.843 353.4802 648.3967 Tm
0 Tc
[(Ho)20(we)18.8(ve)19.7(r,)-309.8(ma)18.4(ny)-301.7(TC)18.6(IM)-308.3(in)20.7(te)19.6(rv)15.1(en)19.7(ti)20.6(on)20.8(s)-317.7(a)0(r)19.7(e)-313.3(be)13.9(ha)19.7(vi)20.7(or)20.9(-)]TJ
-4.1067 -1.1116 TD
[(al)13.8(ly)-278.8(fo)20.9(cu)19.7(se)14.1(d)-289.1(\()0(w)20(i)0(t)20.6(h)-294.8(a)-290.2()56.5(s)21.1(al)19.6(ut)20.7(og)20.8(en)19.7(ic)13.8()62.3()-289.1(em)18.5(ph)15.1(as)19.9(is)-278.6(on)-284.4(li)20.6(fe)19.7(st)15.1(yl)20.7(e)-290.3(a)0(n)19.7(d)]TJ
T*
[(di)14.9(se)19.9(as)19.9(e)-261.4(p)0(r)20.9(e)0(v)19.7(e)0(n)13.9(t)0(i)20.6(o)0(n)20.8(\))0(,)-252.2(r)0(e)19.7(n)0(d)20.8(e)0(r)19.7(i)0(n)20.7(g)-260.3(cl)19.5(in)15(ic)19.5(ia)19.6(n)-260.3(a)0(n)19.7(d)-260.3(pa)19.7(rt)20.7(ic)19.6(ip)14.9(an)19.7(t)-260.4(b)0(l)20.7(i)0(n)20.7(d)0(-)]TJ
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T*
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(9)Tj
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[(Fi)20.9(-)]TJ
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[(as)-245.1(a)-249.9(p)0(r)20.9(o)0(h)20.8(i)0(b)15(i)0(t)20.6(i)0(v)20.7(e)-249.9(ba)19.7(rr)15.1(ie)19.6(r)-248.7(t)0(o)-238.5(r)0(e)14(s)0(e)19.9(a)0(r)19.7(c)0(h)-239.5(f)0(e)14(a)0(s)19.9(i)0(b)20.7(i)0(l)20.6(i)0(t)20.6(y)0(.)]TJ
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(12)Tj
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[(WSR)-455.7(proponents)-455.6(in)-451.6(the)-453.8(TCIM)-456.8(eld)-454.8(were)-456.8(certainly)-457.2(not)]TJ
-1.0137 -1.1174 TD
[(alone)-480.3(in)-474.6(advocating)-481.3(for)-475.5(revisions)-483.2(to)-474.6(methodological)-481.5(con-)]TJ
0 -1.1116 TD
[(ventions)-557.2(in)-555.3(clinical)-560(research;)-561.6(investigators)-558.2(in)-555.3(some)-559.5(bio-)]TJ
T*
[(medical)-410.1(elds)-403.9(\(e.g.,)-406.4(psychotherapy,)-412.8(surgery,)-403.7(and)-407.6(dietetics\))]TJ
0 -1.1174 TD
[(had)-534.4(at)-533.4(the)-528.7(time)-536.9(articulated)-535.6(parallel)-536.8(concerns)-530.5(around)-537.6(the)]TJ
0 -1.1116 TD
[(RCTs)-526.9(universal)-519.1(applicabili)-10.5(ty.)]TJ
7.3823 0 0 6.5614 437.7826 499.351 Tm
(6,13)Tj
9.843 0 0 9.843 455.8109 494.9857 Tm
[(However,)-522(WSR)-524.8(propo-)]TJ
-14.5029 -1.1116 TD
[(nents)-346.4(additionall)-9.3(y)-340.9(pointed)-349(to)-342.1(a)-347.8(unique)-347.7(set)-344.2(of)-342(research)-353(chal-)]TJ
0 -1.1174 TD
[(lenge)-8(s)-317.7(arising)-319.9(from)-316.6(paradigmatic)-324.7(features)-323.2(of)-319(TCIM)-318.5()50.8(whole)]TJ
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[(systems,)43.4()-513.7(i)0(n)-509.2(relation)-518.3(to)-514.9(which)-514.5(these)-514.6(differ)-514.7(substantively)]TJ
T*
[(from)-339.6(conventional)-333.9(biomedical)-338.7(approaches.)]TJ
7.3823 0 0 6.5614 484.044 455.5274 Tm
(5,6)Tj
9.843 0 0 9.843 323.0361 440.2204 Tm
[(As)-227.5(detailed)-231.6(in)-227(Table)-228(1,)-223.4(many)-225.7(whole)-232.3(TCIM)-226.4(systems)-228.5(rely)-224.5(on)]TJ
-1.0137 -1.1174 TD
[(conceptual)-183(models)-176(and)-171.5(diagnostic)-180.6(approaches)-176.7(distinct)-177.3(from)-172.6(or)]TJ
0 -1.1116 TD
[(in)-382.5(addition)-384.7(to)-382.5(biomedical)-390.5(science.)-384.3(Alongside)-386.4(an)-383.5(integrated)]TJ
T*
[(\()49.7(whole)-221.8(person)49(\))-215.2(assessment)-222.4(of)-215.3(a)-215.4(patients)-219.7(physical,)-216.2(mental,)]TJ
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[(emotional,)-322.6(and)-315.5(psychosocial)-321.9(well-being,)-317.5(many)-317.8(TCIM)-318.5(occu-)]TJ
0 -1.1116 TD
[(pations)-360.3(foundationally)-358.1(attend)-354.8(to)-353.7(patient)-356(preferences,)-360.9(priori-)]TJ
T*
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(5,14)Tj
9.843 0 0 9.843 491.4707 374.4566 Tm
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[(engag)-7.8(e)-301.8(objective)-313.3(measures)-312.6(at)-303(discrete)-311.8(endpoints)-310.7(to)-307.6(evaluate)]TJ
0 -1.1116 TD
[(predetermi)-10.2(ned)-298.2(primary)-298.2(treatment)-303(outcomes)-300.3(related)-299.4(to)-296.1(a)-301.8(nar-)]TJ
T*
[(rowly)-219.6(dened)-221.9(disease)-218.3(or)-215.3(dysfunction.)]TJ
7.3823 0 0 6.5614 459.3259 345.9401 Tm
(15,16)Tj
9.843 0 0 9.843 478.0912 341.5747 Tm
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[(multimorbi)-8.2(d)-340.9(i)0(n)-347.9(their)-346.7(aimstypically)-355.8(rely)-345.5(on)-347.8(subjective)-348.8(as-)]TJ
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[(sessment)-363.3(modes)-359.1(to)-353.7(track)-359.3(progressive)-365.5(\(and)-356.9(often)-358.1(long)-355.9(term\))]TJ
T*
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[(inter-)-8(relating)-230.4(symptoms.)]TJ
7.3823 0 0 6.5614 410.003 291.118 Tm
(15,16)Tj
9.843 0 0 9.843 428.8818 286.7527 Tm
[(Finally,)-225.6(while)-232.4(RCTs)-232.1(classically)]TJ
-11.7671 -1.1116 TD
[(evalu)-8(ate)-253.4(an)-256.8(interventions)-259.9(effects)-258.7(before)-256.5(it)-255.9(is)-255.6(being)-254.5(deployed)]TJ
T*
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[(usage)-266.8(before)-262.3(being)-260.2(formally)-264.8(trialed.)]TJ
7.3823 0 0 6.5614 454.7904 258.2928 Tm
(17)Tj
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[(singular,)-624(standardized)-616.9(TCIM)-618(modalities)-625.4(within)-618.4(classical)]TJ
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T*
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(6)Tj
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[(might)-485.1(rigorously)-483.3(compare)-490.5(the)-482.6(real-world)-486.7(effectiveness)-486.5(of)]TJ
T*
[(complex)-627.7(individualized)-624.3(interventions)-621.7(with)-621.8()50.8(usual)48.9()-623.1(bio-)]TJ
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[(genous)-307.1(populations.)]TJ
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(6,1820)Tj
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(6,19)Tj
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[(and)-448(re-)]TJ
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[(commended)-275.1(adoption)-269.4(of)-272.9(more)-266(efcient)-277.3(and)-269.4(equally-rigorous)]TJ
T*
[(design)-7.7(-adaptive)-687.5(allocation)-688.9(alternatives)-697.8(to)-682(randomizat)-10.2(ion)]TJ
T*
[(\(e.g.,)-763.5(minimization\).)]TJ
7.3823 0 0 6.5614 399.118 82.9417 Tm
(21)Tj
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[(Advocating)-763.2(for)-763.5(mixed)-762.6(methods)]TJ
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[(study)-437.4(designs,)-432.5(they)-437.7(argued)-435.1(that)-432(qualitative)-436.7(methods)-436.3(could)]TJ
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/F11 1 Tf
8.9663 0 0 8.9663 62.022 749.6502 Tm
(S22)Tj
48.9393 0 TD
[(IJAZ)-332.6(ET)-338.7(AL.)]TJ
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(1.)Tj
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[(Paradigm)-12148.9(Conceptual)-336.1(model)-14656.9(Diagnostics)-14858.6(Treatment)-340.3(modes)]TJ
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(Ayurvedic)Tj
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(medicine)Tj
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(29,30)Tj
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[(Typological)-331.6(assessment)-342.3(of)-330.2(constitution)]TJ
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[(\))-335(and)-332.4(disequilibrium)-333.6(\()]TJ
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(vikruti)Tj
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[(\)i)335(n)]TJ
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(a)Tj
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[(parameters)-338.2(\(three)]TJ
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(doshas)Tj
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(:)Tj
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(pitta)Tj
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[(\),)-332.6(metabolic)]TJ
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(ama)Tj
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[(\),)-332.6(bodily)]TJ
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[(\),)-332.6(qualities,)]TJ
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T*
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[(manual)-337.9(therapies,)-338.4(enemas)-332.9(and)-338.1(purgation,)]TJ
T*
[(nasal)-335.5(treatments,)-340.8(yoga)-333.4(and)-332.4(meditation,)]TJ
T*
[(breathing)-339.8(exercises,)-333.5(music)-335.5(and)-338.1(mantra,)-335.5(and)]TJ
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(31)Tj
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(typological)Tj
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[(assessment)-325(of)-318.7(whole)-323.8(person)]TJ
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(a)Tj
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[(constitution)-318.9(and)]TJ
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[(disequilibrium)-333.6(in)-336.2(relation)-333.3(to)-336.1(four)-332.2(levels)-336.7(of)]TJ
T*
[(formative)-335.2(forces)-336.4(\(physical,)-337.3(etheric,)-336.6(astral,)]TJ
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[(ego\))-333.4(and)-332.4(threefold)-339.8(structural/functional)]TJ
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[(systems)-337.2(\(nerve-sense,)-336.3(motor-metabolic,)]TJ
T*
(rhythmic\).)Tj
19.8382 6.0753 TD
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(+)Tj
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[(additional)-335.4(narrative)]TJ
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(case-taking.)Tj
19.8382 1.0135 TD
[(Anthroposophic)-338.5(medication)-337.6(\(homeopathic,)]TJ
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[(herbal\),)-335.3(diet)-339.5(and)-332.4(lifestyle)-334.3(counseling,)-338.3(art)]TJ
T*
[(therapy,)-335.3(rhythmical)-336.4(massage)-339.5(therapy,)]TJ
T*
[(Eurythmy)-338.7(movement)-335.2(therapy,)-335.3(biographical)]TJ
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[(counseling,)-309.5(psychotherapy)]TJ
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()Tj
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[(Chinese)-338.5(medicine)]TJ
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(32)Tj
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(a)Tj
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[(constitution)-336.2(\(vital)-335.9(substances\))-336.5(and)]TJ
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[(disequilibrium)-333.6(\(pathogenic)-337.2(factors,)]TJ
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[(stagnations\))-313.8(in)-318.9(relation)-316(to)-313.1(six)-313.9(divisions)-314.3(of)]TJ
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[(tuina)-294.4(massage,)-296.8(cupping,)]TJ
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(,)Tj
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[(qi)-324.6(gong)]TJ
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T*
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T*
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T*
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T*
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T*
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(36)Tj
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T*
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T*
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T*
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T*
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19.8382 1.0135 TD
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21.6637 -1.0135 TD
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[(Swedish)-331.2(massage)]TJ
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(41)Tj
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[(Biomedical)-338.6(assessment)-336.5(with)-333.4(an)-337.2(emphasis)-333.7(on)]TJ
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19.8382 1.0135 TD
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42.4117 -1.0135 TD
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T*
[(touch,)-332.1(and)-332.4(social)-336.7(interaction.)]TJ
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[(Yoga)-334.2(therapy)]TJ
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(43,44)Tj
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[(ex)13.9(pe)19.7(ri)20.7(me)18.4(nt)20.7(al)19.5(,)-285.7(a)0(n)13.9(d)-283.3(ob)20.8(se)14.1(rv)20.9(at)19.5(io)20.7(na)19.7(l;)-278.9(qu)20.8(al)19.5(it)20.6(at)13.8(iv)20.7(e)-284.5(a)0(n)19.7(d)-289.1(qu)20.8(an)19.7(ti)14.8(ta)19.6(ti)20.6(ve)19.7(;)]TJ
0 -1.1116 TD
[(an)13.9(d)-196.9(h)0(o)20.8(l)0(i)20.6(s)0(t)15.1(i)0(c)-187.8(a)0(n)13.9(d)-196.9(re)19.7(du)15.1(ct)19.5(iv)20.7(e)18.6(be)-187.7(eq)13.9(ua)19.7(ll)20.6(y)-202.7(v)0(a)19.7(l)0(u)20.7(e)0(d)-187.7(f)0(o)15.1(r)-196.9(th)15(ei)19.5(r)-196.9(d)0(i)15(s)0(t)20.9(i)0(n)20.7(c)0(t)]TJ
T*
[(co)13.9(nt)20.7(ri)20.7(bu)20.8(ti)20.6(on)15.1(s)-415.6(a)0(n)19.7(d)-421.6(ri)20.7(go)15.1(ro)20.9(us)21(ly)-411.3(ap)19.7(pl)20.7(ie)19.6(d)-421.6(a)0(s)-412.1(c)0(o)19.7(n)0(t)20.7(e)0(x)19.7(t)0(u)15(a)0(l)19.6(l)0(y)-411.3(a)0(p)19.7(p)0(r)20.9(o)0(-)]TJ
0 -1.1174 TD
[(pr)15.1(ia)19.6(te)19.6(.)]TJ
7.3823 0 0 6.5614 84.1322 641.877 Tm
-.0162 Tc
[(6,)-16.2(2)11.9(3)]TJ
9.843 0 0 9.843 99.8362 637.455 Tm
0 Tc
[(As)20.2(se)19.9(rt)15(in)20.7(g)-312.1(t)0(h)20.7(a)0(t)-303(E)0(B)18.6(M)0()20(s)-311.9()62.3()0(p)20.9(r)0(e)14(s)0(c)19.9(r)0(i)20.7(p)0(t)20.7(i)0(v)20.7(e)-313.3(ev)19.7(id)15(en)19.7(ce)-304(hi)20.7(er)19.7(-)]TJ
-4.0721 -1.1116 TD
[(ar)14(ch)19.7(ie)19.6(s)-317.7(o)0(f)-307.4(r)0(e)19.7(s)0(e)14.1(a)0(r)19.7(c)0(h)-308.6(m)0(e)18.4(t)0(h)20.7(o)0(d)20.8(s)0()67.1()-317.8(sh)21(ou)20.8(ld)-307.6(be)-308.6(su)15.3(pp)20.8(la)19.6(nt)20.7(ed)19.7(,)]TJ
7.3823 0 0 6.5614 264.1322 630.8786 Tm
(20)Tj
9.843 0 0 9.843 274.5637 626.5132 Tm
[(TC)18.6(IM)]TJ
-21.8235 -1.1116 TD
[(sc)14.1(ho)20.8(la)19.6(rs)-595.2(va)19.7(ri)20.7(ou)20.8(sl)15.1(y)-600.1(c)0(o)19.7(n)0(c)13.9(e)0(p)19.7(t)0(u)20.7(a)0(l)19.5(i)0(z)19.6(e)0(d)-596.6(e)0(v)19.7(i)0(d)20.7(e)0(n)19.7(t)0(i)20.6(a)0(r)14(y)-600.1(fr)15.1(am)18.4(ew)18.8(or)20.9(ks)]TJ
0 -1.1174 TD
[(\(e)14(.)13.9(g)0(.)18.5(,)-182()62.3()0(e)19.7(v)0(i)20.7(d)0(e)13.9(n)0(c)19.7(e)-180.8(ma)18.4(tr)20.7(ix)20.7(,)70.4()]TJ
7.3823 0 0 6.5614 156.6425 608.9951 Tm
(24)Tj
9.843 0 0 9.843 165.7133 604.5731 Tm
-.02 Tc
[()36.5()-20(ev)-20(id)-20(en)-20(ce)-200.8(h)-20(o).8(u)-20(s)-4.7(e)-20(,)3.1()36.5()]TJ
7.3823 0 0 6.5614 238.5637 608.9951 Tm
-.0162 Tc
(25)Tj
9.843 0 0 9.843 247.6346 604.5731 Tm
0 Tc
[(an)19.7(d)-179.6()62.3(c)19.7(ir)15(cu)19.7(la)19.6(r)]TJ
-19.0877 -1.1116 TD
[(mo)19.6(de)13.9(l)72.6()]TJ
7.3823 0 0 6.5614 89.8582 597.9967 Tm
(19)Tj
9.843 0 0 9.843 97.0582 593.6313 Tm
[(\))-369.7(i)0(n)-359.4(w)0(h)20(i)0(c)19.5(h)-369.7(a)-370.9(r)0(a)19.7(n)0(g)20.8(e)-370.9(of)-359.3(re)14(se)19.9(ar)19.7(ch)-360.5(de)19.7(si)20.9(gn)15.1(s)-363.8(m)0(i)13.7(g)0(h)20.8(t)-369.8(sy)21(n-)]TJ
-3.7899 -1.1116 TD
[(th)15(et)19.5(ic)19.6(al)19.5(ly)-422.8(co)19.7(nt)20.7(ri)20.7(bu)20.8(te)-423.9(to)-417(as)14.1(se)19.9(ss)21.2(in)15(g)-427.3(a)-428.5(pa)13.9(rt)20.7(ic)19.6(ul)20.7(ar)-423.8(in)20.7(te)19.6(rv)20.9(en)19.7(ti)14.8(on)20.8(s)]TJ
T*
[(ef)14(c)19.8(ac)18.5(y,)-240.7(ef)19.7(fe)19.7(ct)19.5(iv)20.7(en)13.9(es)19.9(s,)-240.5(an)19.7(d)-248.8(o)0(t)20.7(h)0(e)13.9(r)-248.7(co)19.7(nt)20.7(ex)19.7(tu)20.7(al)-245.4(di)20.7(me)18.4(ns)21(io)20.7(ns)15.3(.)]TJ
1.0137 -1.1174 TD
[(Ta)18.5(ki)20.7(ng)-342(on)-347.8(mo)19.6(de)19.7(l)-352.6(v)0(a)19.7(l)0(i)20.6(d)0(i)20.7(t)0(y)-347.9(w)0(i)19.8(t)0(h)-342.1(r)0(e)19.7(s)0(p)21(e)0(c)18.5(t)-358.3(to)-342.1(in)20.7(te)19.6(rv)20.9(en)19.7(ti)14.8(on)-342(se)19.9(-)]TJ
-1.0137 -1.1116 TD
[(le)13.8(ct)19.5(io)20.7(n)-277.6(a)0(n)19.7(d)-277.6(de)19.7(si)20.9(gn)15.1(,)-274.1(W)0(S)18.7(R)-278.6(ad)19.7(vo)20.8(ca)18.5(te)13.8(s)-277.4(f)0(a)19.7(v)0(o)20.8(r)0(e)19.7(d)-277.6(th)20.7(e)-278.7(e)0(v)19.7(a)0(l)13.8(u)0(a)19.7(t)0(i)20.6(o)0(n)-267.1(o)0(f)]TJ
T*
[()56.5()0(w)20(h)0(o)20.8(l)0(e)-631.3(s)0(y)21(s)0(t)20.9(e)0(m)18.5(s)0(,)-626.4(o)0(r)-630()0(b)20.9(u)0(n)20.8(d)0(l)20.7(e)0(s)14.1()-634.6(of)-624.2(th)15(er)19.7(ap)19.7(ie)19.6(s)67.1()-634.6(r)0(a)19.7(t)0(h)20.7(e)0(r)-631.1(t)0(h)20.7(a)0(n)]TJ
0 -1.1174 TD
-.0208 Tc
[()35.7()-20.8(si)-20.8(ng)-20.8(le)]TJ
/F16 1 Tf
2.9375 0 TD
0 Tc
(.)Tj
/F6 1 Tf
.9849 0 TD
[(mo)19.6(da)13.9(li)20.6(ti)20.6(es)19.9()56.5()-628.9(al)19.5(on)20.8(e.)]TJ
7.3823 0 0 6.5614 174.1039 532.2329 Tm
(6)Tj
9.843 0 0 9.843 184.0251 527.8676 Tm
[(Th)19.6(ey)-619.6(en)19.7(vi)20.7(si)15.1(on)20.8(ed)-619.6(st)20.9(ud)20.8(ie)13.8(s)-628.7(i)0(n)]TJ
-12.6253 -1.1116 TD
[(wh)14.2(ic)19.6(h)-335.2(p)0(a)19.7(t)0(i)20.6(e)0(n)13.9(t)0(s)-324.7(w)0(o)20(u)0(l)14.9(d)-335.2(un)20.8(de)19.7(rg)15.1(o)-335.2()62.3(d)15.1(ou)20.8(bl)20.7(e)-336.3(c)0(l)13.8(a)0(s)19.9(s)0(i)20.9()0(c)19.8(a)0(t)19.6(i)0(o)14.9(n)0()72.7()-340.9(us)21(in)20.7(g)]TJ
T*
[(bi)14.9(om)19.6(ed)19.7(ic)19.5(al)-314.5(di)20.7(ag)19.7(no)20.8(st)20.9(ic)13.8(s,)-309.6(as)-314.2(we)18.8(ll)-313.5(as)-308.4(di)14.9(ag)19.7(no)20.8(si)20.9(s)-323.4(f)0(r)20.9(o)0(m)-314.4(w)0(i)19.8(t)0(h)20.7(i)0(n)-313.3(t)0(h)20.7(e)]TJ
0 -1.1174 TD
[(re)14(le)19.6(va)19.7(nt)-319.1(TC)18.6(IM)-325.6(pa)19.7(ra)19.7(di)20.7(gm)19.6(,)-331.7(a)0(n)19.7(d)-329.4(re)19.7(ce)12.8(iv)20.7(e)-330.6(c)0(a)18.5(r)0(e)-320.1(t)0(h)15(a)0(t)-320.3(w)0(a)18.8(s)-329.2(in)15(di)20.7(vi)20.7(d-)]TJ
0 -1.1116 TD
[(ua)13.9(li)20.6(ze)18.5(d)-346.7(o)0(n)-330.5(t)0(h)20.7(i)0(s)-336.2(b)0(a)13.9(s)0(i)20.9(s)0(.)]TJ
7.3823 0 0 6.5614 143.2629 488.4093 Tm
(6)Tj
9.843 0 0 9.843 150.3496 484.0439 Tm
[(Re)18.6(se)19.9(ar)19.7(ch)-337.4(te)19.6(am)18.5(s,)-338.4(th)20.7(ey)-337.4(ad)19.7(vi)20.7(se)19.9(d,)-332.8(sh)15.3(ou)20.8(ld)]TJ
-9.204 -1.1116 TD
[(in)15(cl)19.5(ud)20.8(e)-347.8(i)0(n)20.7(s)0(i)20.9(d)0(e)13.9(r)0(s)-336(f)0(r)20.9(o)0(m)-337.5(w)0(i)19.8(t)0(h)15(i)0(n)-336.4(t)0(h)20.7(e)-347.8(pa)19.7(ra)19.7(di)14.9(gm)19.6(s)-346.5(i)0(n)-336.4(w)0(h)20(i)0(c)19.6(h)-352.4(th)20.7(e)-347.8(i)0(n)20.7(-)]TJ
0 -1.1174 TD
[(te)13.8(rv)20.9(en)19.7(ti)20.6(on)20.8(s)-450.2(o)0(r)20.9(i)0(g)15(i)0(n)20.7(a)0(t)19.6(e)0(d)]TJ
7.3823 0 0 6.5614 146.211 466.5258 Tm
[(26)24.7(,2)28.1(7)]TJ
9.843 0 0 9.843 162.3685 462.1038 Tm
[(;)-450.5(a)0(n)19.7(d)-444.6(st)15.1(ud)20.8(y)-450.4(r)0(e)19.7(c)0(r)19.7(u)0(i)20.7(t)0(m)19.5(e)0(n)19.7(t)-450.5(st)20.9(ra)14(te)19.6(gi)20.7(es)]TJ
-10.4251 -1.1116 TD
[(sh)15.3(ou)20.8(ld)-422.8(ad)19.7(dr)20.9(es)19.9(s)-432.9(p)0(e)19.7(r)0(s)15.3(o)0(n)20.8(s)-432.9(wi)19.8(th)-422.8(co)19.7(mp)19.6(le)19.6(x,)-425(mu)19.6(lt)20.6(if)20.7(ac)18.5(to)15(ri)20.7(al)-424(he)19.7(al)19.5(th)]TJ
T*
[(co)13.9(nd)20.8(it)20.6(io)20.7(ns)21(,)]TJ
7.3823 0 0 6.5614 102.274 444.5857 Tm
(28)Tj
9.843 0 0 9.843 112.7622 440.2204 Tm
[(as)-314.2(we)18.8(ll)-313.5(as)-314.2(pa)19.7(ti)20.6(en)13.9(t)-323.8(t)0(r)20.7(e)0(a)18.5(t)0(m)19.5(e)0(n)19.7(t)-323.8(pr)20.9(ef)19.7(er)14(en)19.7(ce)18.5(s.)]TJ
7.3823 0 0 6.5614 271.4456 444.5857 Tm
-.0162 Tc
(14)Tj
9.843 0 0 9.843 69.7323 429.2786 Tm
0 Tc
[(WS)18.7(R)-221(l)0(e)19.6(a)0(d)19.7(e)0(r)19.7(s)-219.8(eq)19.7(ua)19.7(ll)14.8(y)-214.2(e)0(n)19.7(v)0(i)14.9(s)0(i)20.9(o)0(n)20.8(e)0(d)-210.7(s)0(t)20.9(u)0(d)20.8(y)-220(ou)20.8(tc)19.6(om)19.6(e)-221.1(a)0(s)19.9(s)0(e)14.1(s)0(s)21.2(m)0(e)18.4(n)0(t)]TJ
-1.0137 -1.1174 TD
[(in)-353.7(re)19.7(la)13.8(ti)20.6(on)-353.5(to)-353.7(th)20.7(e)-359.4(m)0(o)19.6(d)0(e)13.9(l)-358.3(va)19.7(li)14.8(di)20.7(ty)-353.7(pr)20.9(in)20.7(ci)19.5(pl)14.9(e.)]TJ
7.3823 0 0 6.5614 228.359 422.6456 Tm
(6)Tj
9.843 0 0 9.843 235.6157 418.2802 Tm
[(At)-354.5(a)-365.1(t)0(i)20.6(m)0(e)-355.9(w)0(h)20(e)0(n)]TJ
-17.8666 -1.1116 TD
[(va)13.9(li)20.6(da)19.7(te)19.5(d,)-269.5(pa)19.7(ti)20.6(en)19.7(t-)20.7(re)19.7(po)15.1(rt)20.7(ed)-268.3(ou)20.8(tc)19.6(om)19.6(e)-278.7(m)0(e)18.4(a)0(s)19.9(u)0(r)20.9(e)0(s)-268.1(\()0(P)15.3(R)0(O)18.9(M)0(s)20.1(\))-277.5(we)18.8(re)]TJ
T*
[(ju)15(st)-411.1(be)19.7(gi)20.7(nn)15.1(in)20.7(g)-421.6(t)0(o)-411.3(b)0(e)-418.1(w)0(i)19.8(d)0(e)19.7(l)0(y)-417(u)0(s)21(e)0(d)-412.3(i)0(n)-417(c)0(o)19.7(n)0(v)20.8(e)0(n)19.7(t)0(i)20.6(o)0(n)20.8(a)0(l)-418.2(r)0(e)19.7(s)0(e)19.9(a)0(r)19.7(c)0(h)19.7(,)]TJ
0 -1.1174 TD
[(WS)18.7(R)-618.4(p)0(r)20.9(o)0(p)15.1(o)0(n)20.8(e)0(n)19.7(t)0(s)-606.9(c)0(h)19.7(a)0(r)19.7(a)0(c)18.5(t)0(e)13.8(r)0(i)20.7(z)0(e)18.5(d)-617.4(su)21(bj)20.7(ec)18.5(ti)14.8(ve)-602.4(an)13.9(d)-611.6(p)0(a)13.9(r)0(a)19.7(d)0(i)20.7(g)0(m)19.6(-)]TJ
0 -1.1116 TD
[(ad)13.9(he)19.7(re)19.7(nt)-198.2(qu)15.1(an)19.7(ti)20.6(ta)19.5(ti)20.6(ve)-205(ou)20.8(tc)19.6(om)19.6(e)-209.6(m)0(e)18.4(a)0(s)14.1(u)0(r)20.9(e)0(s)]TJ
7.3823 0 0 6.5614 214.4125 378.8219 Tm
[(15)24.7(,2)28.1(2)]TJ
9.843 0 0 9.843 232.7243 374.4566 Tm
[(as)-204.8(ke)19.7(y)-208.4(e)0(v)13.9(a)0(l)19.5(u)0(a)19.7(t)0(i)20.6(v)0(e)]TJ
-17.5729 -1.1116 TD
[(to)15(ol)20.7(s,)-591.8(al)19.5(on)20.8(gs)15.3(id)20.7(e)-601.3(q)0(u)15.1(a)0(l)19.5(i)0(t)20.6(a)0(t)19.5(i)0(v)20.7(e)-607(me)18.4(th)20.7(od)20.8(s.)]TJ
7.3823 0 0 6.5614 211.748 367.8802 Tm
(22)Tj
9.843 0 0 9.843 225.0141 363.5149 Tm
[(Me)18.8(as)19.9(ur)20.9(ab)19.7(le)19.6(s,)-597.6(th)20.7(ey)]TJ
-16.7895 -1.1174 TD
[(pr)15.1(op)20.8(os)21(ed)19.7(,)-585.2(s)0(h)15.3(o)0(u)20.8(l)0(d)-578.3(b)0(e)-573.6(m)0(u)19.6(l)0(t)14.8(i)0(p)20.7(l)0(e)-579.5(\()0(a)19.7(d)0(d)20.8(r)0(e)19.7(s)0(s)15.5(i)0(n)20.7(g)-582.8(th)15(e)-584(t)0(h)20.7(e)0(r)14(a)0(p)19.7(e)0(u)19.7(t)0(i)20.6(c)]TJ
0 -1.1116 TD
[(te)13.8(ch)19.7(ni)20.7(qu)20.8(es)-147.2(ap)19.7(pl)20.7(ie)19.5(d,)-148.5(pa)19.7(ti)20.6(en)19.7(t)15(pr)20.9(ac)18.5(ti)20.6(ti)20.6(on)20.8(er)-147.3(re)14(la)19.6(ti)20.6(on)20.8(sh)21(ip)15(,)-153.2(a)0(n)19.7(d)-156.6(ra)19.7(ng)20.8(e)]TJ
T*
[(of)-215.3(he)19.7(al)19.5(th)20.7(/w)14.1(el)19.5(ln)20.7(es)19.9(s)-225.5(i)0(m)19.5(p)0(a)19.7(c)0(t)19.5(s)]TJ
7.3823 0 0 6.5614 161.8582 334.9983 Tm
[(15)24.7(,4)20.4(5)]TJ
9.843 0 0 9.843 178.0157 330.633 Tm
[(\))-225.7(a)0(n)19.7(d)-220(at)-216.6(mo)19.6(re)-210.7(fr)20.9(eq)13.9(ue)19.7(nt)-209.7(in)20.7(te)13.8(rv)20.9(al)19.5(s)]TJ
-12.0147 -1.1116 TD
[(an)13.9(d)-277.6(o)0(v)20.8(e)0(r)-268.3(a)-278.7(lo)20.7(ng)15.1(er)-268.3(pe)19.7(ri)20.7(od)-267.1(th)15(an)-268.3(in)-267.3(co)19.7(nv)20.8(en)19.7(ti)14.8(on)20.8(al)-268.4(tr)20.7(ia)19.5(ls)15.2(.)]TJ
7.3823 0 0 6.5614 262.7149 324.0566 Tm
[(16)24.7(,2)20.4(3)]TJ
9.843 0 0 9.843 281.707 319.6913 Tm
-.0565 Tc
[()-56.5(I)-35.6(n)-56.5(-)]TJ
-22.5492 -1.1174 TD
0 Tc
[(no)15.1(va)19.7(ti)20.6(ve)-400.8(st)20.9(at)19.5(is)15.1(ti)20.6(ca)18.5(l)-410.2(m)0(e)18.4(t)0(h)20.7(o)0(d)20.8(o)0(l)14.9(o)0(g)20.8(y)0()72.7()]TJ
7.3823 0 0 6.5614 194.5133 313.0582 Tm
(6)Tj
9.843 0 0 9.843 198.1417 308.6928 Tm
[(i)19.6(nc)19.7(lu)20.7(di)20.7(ng)-405.4()62.3()0(p)20.9(a)0(r)19.7(t)0(i)14.8(c)0(i)19.6(p)0(a)19.7(n)0(t)20.7(-)]TJ
-14.0594 -1.1116 TD
[(ce)18.5(nt)14.9(er)19.7(ed)19.7()62.3()-329.4(ap)19.7(pr)20.9(oa)13.9(ch)19.7(es)]TJ
7.3823 0 0 6.5614 145.1338 302.1165 Tm
-.0162 Tc
(46)Tj
9.843 0 0 9.843 152.3338 297.7511 Tm
0 Tc
[(w)18.9(ou)20.8(ld)-319.1(be)-320.1(ne)19.7(ed)19.7(ed)-320.1(to)-313.4(sy)15.3(nt)20.7(he)19.7(si)20.9(ze)-321.3(th)20.7(e)]TJ
-9.4056 -1.1116 TD
[(vo)15.1(lu)20.7(mi)19.5(no)20.8(us)-318.8(da)19.7(ta)-320.3(ge)19.7(ne)19.7(ra)19.7(te)19.5(d.)]TJ
7.3823 0 0 6.5614 168.0378 291.1747 Tm
(6)Tj
9.843 0 0 9.843 174.9543 286.8094 Tm
[(Th)19.6(ey)-320.1(ca)18.5(ll)20.6(ed)-320.1(fo)20.9(r)-323.6()56.5(c)19.7(om)19.6(pl)20.7(ex)-320.1(co)19.7(n-)]TJ
-11.7037 -1.1174 TD
[(ce)18.5(pt)14.9(ua)19.7(l)-433.2(m)0(o)19.6(d)0(e)19.7(l)0(s)20.9()56.5()]TJ
7.3823 0 0 6.5614 125.8582 280.1763 Tm
-.0162 Tc
(16)Tj
9.843 0 0 9.843 137.4236 275.8109 Tm
0 Tc
[(to)-422.8(ev)19.7(al)13.8(ua)19.7(te)-423.9(a)-434.2(w)0(h)20(o)0(l)14.9(e)-434.2(sy)21(st)20.9(em)18.5(s)-428.2(co)19.7(mb)19.6(in)20.7(ed)]TJ
-7.8908 -1.1116 TD
[(ef)14(fe)19.7(ct)19.5(s)-271.6()56.5(o)20.9(ve)19.7(r)-271.8(a)0(n)19.7(d)-271.8(ab)13.9(ov)20.8(e)-273(i)0(t)20.6(s)-271.6(co)13.9(m)15(p)0(o)15.1(n)0(e)19.7(n)0(t)20.7(s)0()67.1()]TJ
7.3823 0 0 6.5614 221.0456 269.2346 Tm
(6)Tj
9.843 0 0 9.843 227.3952 264.8692 Tm
[(an)19.7(d)-277.6(v)0(a)19.7(r)0(i)20.7(o)0(u)20.8(s)0(l)20.9(y)-277.6(pr)20.9(o-)]TJ
-17.0315 -1.1116 TD
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0 -1.1174 TD
[(co)13.9(m)15(p)0(l)15(e)0(x)19.7(i)0(t)20.6(y)-323.6(sc)14.1(ie)19.6(nc)19.7(e)-324.8(a)0(n)19.7(d)-329.4(no)20.8(nl)20.7(in)20.7(ea)18.5(r)-329.4(d)0(y)20.8(n)0(a)19.7(m)0(i)19.5(c)0(a)18.5(l)-323.8(sy)15.3(st)20.9(em)18.5(s,)]TJ
7.3823 0 0 6.5614 271.8424 247.3511 Tm
[(2)16.2(3)0(,)20.4(4)16.2(7)24.7(49)]TJ
9.843 0 0 9.843 59.7543 231.9873 Tm
[(ac)18.5(ti)14.8(on)-238.3(re)19.7(se)19.9(ar)13.9(ch)19.7(,)]TJ
7.3823 0 0 6.5614 120.4157 236.3527 Tm
[(7,)20.4(1)16.2(6)]TJ
9.843 0 0 9.843 135.5527 231.9873 Tm
[(an)19.7(d)-248.8(p)0(r)15.1(o)0(g)20.8(r)0(a)19.7(m)-250(th)20.7(eo)19.7(ry)]TJ
7.3823 0 0 6.5614 212.0314 236.3527 Tm
-.0162 Tc
(16)Tj
9.843 0 0 9.843 221.7826 231.9873 Tm
0 Tc
[(to)-238.5(th)20.7(is)-244(en)19.7(d.)]TJ
-15.4475 -1.1116 TD
[(Since)-382.2(2003,)-382.2(the)-384.7(dominant)-385.9(landscape)-383.1(of)-382.3(clinical)-387.2(research)]TJ
-1.0137 -1.1174 TD
[(has)-424.7(transformed)-430.2(signicantly.)-428.1(Although)-424.6(the)-425.1(classical)-429.3(RCT)]TJ
0 -1.1116 TD
[(continues)-334.9(to)-330.6(be)-325.9(prioritized)-331.7(in)-330.6(EBMs)-331(evidentiary)-332.8(hierarchy,)]TJ
T*
[(pragmatically)-562.1(designed)-552.5(comparative)-553.9(effectiveness)-561.4(studies)]TJ
T*
[(and)-332.8()50.8(t-for-purpose)45()-329.4(research)-335.7(designs)]TJ
7.3823 0 0 6.5614 215.7165 181.5874 Tm
(1)Tj
9.843 0 0 9.843 222.6897 177.222 Tm
[(have)-329.3(become)-333.9(more)]TJ
-16.5534 -1.1174 TD
[(widely)-510(accepted)-510.1(as)-504.3(important)-508(clinical)-508.2(and)-505.6(policy-making)]TJ
0 -1.1116 TD
(resources.)Tj
7.3823 0 0 6.5614 99.4393 159.6472 Tm
(50)Tj
9.843 0 0 9.843 110.0976 155.2818 Tm
[(Usage)-331.1(of)-330.5(PROMs,)-328.2(clinical)-335.4(trial)-329.6(guidelines,)-328(and)]TJ
-5.1146 -1.1116 TD
[(quality)-297.2(assessment)-297.3(tools)-287.8(has)-298(become)-293.6(more)-289(widespread;)-298.7(and,)]TJ
0 -1.1174 TD
[()50.8(following)-611.2(considerable)-611.2(development)-610.4(in)-601.3(the)-609.4(eld,)47.6()-600.1(the)]TJ
0 -1.1116 TD
[(Medical)-254.3(Research)-256.2(Councils)-254.1(framework)-256.2(for)-245.1(trialing)-252.4(complex)]TJ
T*
[(interventions)-368.3(will)-357(once)-363.8(again)-359.3(be)-360.5(renewed)-363.4(in)-359.4(2019.)]TJ
7.3823 0 0 6.5614 264.1889 115.8235 Tm
(2)Tj
9.843 0 0 9.843 271.3889 111.4582 Tm
(Within)Tj
-21.501 -1.1174 TD
[(the)-453.8(TCIM)-451(world,)-453.4(WSR)-455.7(principles)-451.2(have)-450.2(been)-456(increasingly)]TJ
0 -1.1116 TD
[(taken)-445.7(up,)]TJ
7.3823 0 0 6.5614 97.8519 93.8834 Tm
[(43,5)-8.6(155)]TJ
9.843 0 0 9.843 129.9968 89.5181 Tm
[(although)-442.2(more)-444.5(conventional)-449.1(research)-445.2(de-)]TJ
-7.1363 -1.1116 TD
[(signs)-523.6(still)-518.4(predominate.)]TJ
7.3823 0 0 6.5614 156.9259 82.9417 Tm
(56)Tj
9.843 0 0 9.843 169.3984 78.5763 Tm
[(To)-516(date,)-522.9(however,)-521.2(no)-514.8(compre-)]TJ
-11.1393 -1.1174 TD
[(hensive)-418.9(retrospective)-422.3(analysis)-419.9(of)-411.1(WSR)-421.1(advances)-416.5(has)-419(been)]TJ
0 -1.1116 TD
[(undertaken;)-338.4(that)-334.1(is)-336.2(thus)-332.6(the)-332.9(present)-338.2(works)-335.5(aim.)]TJ
/F4 1 Tf
8.9663 0 0 8.9663 310.8472 725.7825 Tm
(Methods)Tj
/F6 1 Tf
9.843 0 0 9.843 320.8251 709.3416 Tm
[(Th)13.9(is)-485.9(ar)14(tic)18.3(le)-493.1(is)-485.9(a)-497.6(s)0(c)14.1(o)0(p)15.1(ing)-481.5(rev)18.6(ie)13.8(w)-497.3(o)0(f)-491.7(t)0(h)15(e)-497.6(me)12.7(th)15(od)15.1(ol)14.9(ogi)19.6(ca)12.8(l)]TJ
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[(fe)14(at)13.8(ur)15.1(es)-250.8(of)-244.1(WS)13(R)-249.8(s)0(t)15.1(udi)19.6(es)14.1(,)-251.1(wit)18.6(h)-254.5(r)0(e)14(f)0(e)14(r)0(e)13.9(nce)-241.8(to)-244.2(th)15(e)-255.7(m)0(o)13.9(d)0(e)13.9(l)-248.9(va)13.9(lid)19.5(it)14.8(y)]TJ
0 -1.1174 TD
[(pr)15.1(in)15(ci)13.8(ple)18.4(.)-233.8(Sco)18.7(pin)19.6(g)-237.2(r)0(e)13.9(v)0(i)14.9(e)0(w)13(s)-237()56.5()0(m)13.9(a)0(p)-228(t)0(h)15(e)-238.4(li)14.8(te)13.8(rat)18.5(ure)-223.3(on)-226.8(a)-238.4(p)0(a)13.9(r)0(t)15(icu)18.4(la)13.8(r)]TJ
0 -1.1116 TD
[(to)15(pi)14.9(c)-301.8(o)0(r)-290.1(r)0(e)14(s)0(e)14.1(a)0(r)14(c)0(h)-291.3(are)17.4(a)-301.8(a)0(n)13.9(d)-294.8(pro)19.8(vi)14.9(de)-291.3(an)-291.3(opp)19.7(ort)19.6(un)15.1(ity)-285.8(to)-290.3(id)15(ent)18.4(if)15(y)]TJ
T*
[(ke)13.9(y)-300.6(c)0(o)13.9(n)0(c)13.9(ept)18.4(s;)-295.9(ga)13.9(ps)-295.7(in)-296.1(th)15(e)-301.8(r)0(e)14(s)0(e)14.1(arc)17.4(h;)-296.1(an)13.9(d)-300.6(t)0(y)15(pes)-292.3(an)13.9(d)-300.6(s)0(o)15.3(urc)18.6(es)-296.9(of)]TJ
0 -1.1174 TD
[(ev)13.9(id)15(en)13.9(ce)-315.5(to)-313.4(in)14.9(for)19.8(m)-319.1(pra)18.6(ct)13.8(ice)17.3(,)-320.2(p)0(o)15.1(l)0(i)14.8(cym)17.3(ak)13.9(in)15(g,)-315.6(an)13.9(d)-317.9(res)18.8(ea)12.8(rch)18.6(.)64.6()]TJ
7.3823 0 0 6.5614 542.6077 658.9415 Tm
(57)Tj
9.843 0 0 9.843 310.8472 643.5778 Tm
[(Sc)14.1(op)15.1(in)15(g)-329.4(r)0(e)14(v)0(i)14.9(e)0(w)13.1(s)-329.2()62.3(di)19.6(ffe)18.6(r)-323.6(fro)19.8(m)-324.9(sys)20.1(tem)17.2(at)13.8(ic)-320.3(re)14(vi)14.9(ews)-316.2(as)-320(au)13.9(th)15(or)15.1(s)]TJ
0 -1.1116 TD
[(do)-347.8(no)15.1(t)-358.3(t)0(y)15(p)0(i)14.9(c)0(a)12.8(l)0(l)14.8(y)-358.2(as)14.1(se)14.1(ss)-353.1(th)15(e)-353.6(qua)18.6(li)14.8(ty)-347.9(of)65.9()]TJ
7.3823 0 0 6.5614 464.8251 637.0014 Tm
(58)Tj
9.843 0 0 9.843 475.6534 632.636 Tm
[(no)15.1(r)-358.2()56.5(s)15.3(ee)12.8(k)-358.2(t)0(o)-347.9()0(s)15.3(y)0(n)15.1(-)]TJ
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0 -1.1174 TD
[(st)15.1(ud)15.1(ies)18.6(.)64.6()]TJ
7.3823 0 0 6.5614 346.0535 615.0613 Tm
(59)Tj
9.843 0 0 9.843 357.5054 610.6959 Tm
[(Th)13.9(ey)-406.5(als)18.6(o)-421.6(d)0(i)14.9(v)0(e)13.9(r)0(g)15.1(e)-417(fro)19.8(m)-417()56.5(na)18.6(rr)15.1(ati)18.3(ve)-412.3(or)-411.1(li)14.8(te)13.8(rat)18.5(ure)]TJ
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[(re)14(vi)14.9(ew)13.1(s)-352.2(i)0(n)-342.1(tha)18.4(t)-352.6(t)0(h)14.9(e)-353.6(sc)14.1(op)15.1(ing)-337.5(pro)19.8(ce)12.8(ss)-347.4(re)13.9(qu)15.1(ire)18.5(s)-352.2(a)0(n)13.9(a)0(l)13.8(y)0(t)14.9(ica)17.3(l)-352.6(r)0(e)13.9(i)0(n)14.9(-)]TJ
T*
[(te)13.8(rp)15.1(re)14(tat)18.3(ion)-274.1(of)-284.4(th)15(e)-290.2(l)0(i)14.8(t)0(e)13.8(r)0(a)14(t)0(u)15(re.)16.3()56.5()]TJ
7.3823 0 0 6.5614 427.6912 593.1778 Tm
(58)Tj
9.843 0 0 9.843 437.8959 588.8124 Tm
[()62.3(No)18.9(t)-289.2(l)0(i)14.8(n)0(e)13.9(a)0(r)-285.5(b)0(u)15.1(t)-289.2(it)14.8(er)14(at)13.8(ive)18.5()56.5()-289(in)]TJ
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[(ch)13.9(ar)14(ac)12.8(te)13.8(r,)-367.4(sc)14.1(op)15.1(ing)-360.5(re)14(vi)14.9(ew)13.1(s)-375.3(p)0(r)15.1(i)0(m)13.7(a)0(r)13.9(i)0(l)14.8(y)-375.5(ta)13.8(ke)-360.5(a)-370.9(qua)18.6(lit)19.4(at)13.8(ive)-361.7(an)13.9(a-)]TJ
0 -1.1116 TD
[(ly)15(ti)14.8(c)-313.3(a)0(p)13.9(p)0(r)15.1(o)0(a)13.9(ch,)-300.5(su)15.3(pp)15.1(or)15.1(ted)-298.3(by)-301.7(num)18.5(er)13.9(ic)13.8(al)-308.8(re)14(pr)15.1(es)14.1(ent)18.4(at)13.8(ion)-297.2(of)-301.7(the)]TJ
T*
[()56.5()0(e)14(x)0(t)14.9(e)0(n)13.9(t)0(,)-321.4(n)0(a)13.9(t)0(u)15(re,)-317.8(an)13.9(d)-323.6(d)0(i)14.9(str)19.8(ibu)19.6(tio)19.5(n)61.2()-323.6(o)0(f)-318.9(k)0(e)13.9(y)-329.4(n)15.2(di)14.9(ng)15.1(s.)]TJ
7.3823 0 0 6.5614 509.6691 560.2959 Tm
(59)Tj
9.843 0 0 9.843 320.8251 544.9321 Tm
[(The)-431.9(present)-436.2(review)-436.1(adopts)-433.9(Arksey)-434.6(and)-430.7(OMalleys)-441.3(six-)]TJ
-1.0137 -1.1116 TD
[(step)-685.1(scoping)-688.5(study)-685.1(framework,)-691.6(involving:)-685.4(\(1\))-688.6(research)]TJ
T*
[(question)-511.1(identication;)-514.9(\(2\))-510.1(study)-512.3(identication;)-514.9(\(3\))-510.1(study)]TJ
0 -1.1174 TD
[(selection;)-412.3(\(4\))-412.2(data)-415.8(charting;)-410(\(5\))-412.2(result)-411(collation,)-413.6(summary,)]TJ
0 -1.1116 TD
[(and)-563.2(reporting;)-565.4(and)-563.2(\(6\))-567.7(\(optional\))-565.4(consultation)-568.8(with)-564.2(area)]TJ
T*
[(experts)-332.5(to)-336.4(validate)-335.2(ndings.)]TJ
7.3823 0 0 6.5614 422.4188 494.5322 Tm
(59)Tj
/F14 1 Tf
8.9663 0 0 8.9663 310.8472 467.9999 Tm
[(Research)-331.4(question)-338.3(identication)]TJ
/F6 1 Tf
9.843 0 0 9.843 320.8251 451.5589 Tm
[(The)-362.8(primary)-367.3(question)-367.1(driving)-370.8(this)-367.3(review)-367(is)-365(twofold,)-369.3(in-)]TJ
-1.0137 -1.1116 TD
[(terrogating:)-367.3(\(1\))-371.9(the)-367.5(range)-370.7(and)-367.3(characteristics)-374.9(of)-365(WSR)-369.3(clin-)]TJ
T*
[(ical)-323.8(studies)-325.5(and)-327(\(2\))-325.8(the)-321.4(ways)-328.8(in)-324.9(which)-324.5(these)-324.6(studies)-331.3(engage)]TJ
0 -1.1174 TD
(the)Tj
/F15 1 Tf
1.5609 0 TD
[(model)-336(validity)]TJ
/F6 1 Tf
6.1341 0 TD
(principle.)Tj
/F14 1 Tf
8.9663 0 0 8.9663 310.8472 396.5101 Tm
[(Study)-332.3(identication)]TJ
/F6 1 Tf
9.843 0 0 9.843 320.8251 380.0692 Tm
-.0193 Tc
[(W)-5.4(S)-19.3(R)-5.1(-)-19.3(ty)-19.3(pe)-280.7(s)-19.3(t)1.6(u)-19.3(d)-4.2(i)-19.3(e).3(s)-279.4(h)-19.3(av)-19.3(e)-276.1(b)-19.3(ee)-19.3(n)-270.3(u)-19.3(nd)-19.3(er)-19.3(ta)-19.3(ke)-19.3(n)-270.3(i)-19.3(n)-269.3(m)-19.3(ul)-19.3(ti)-19.3(pl)-19.3(e)-270.5(h)-19.3(ea)-19.3(lt)-19.3(h)]TJ
-1.0137 -1.1116 TD
0 Tc
[(ca)18.5(re)-481.4(pa)19.7(ra)19.7(di)20.7(gm)19.6(s,)-482.4(an)19.7(d)-490.7(t)0(h)20.7(e)-491.8(me)18.4(th)20.7(od)20.8(ol)20.7(og)15.1(ic)19.5(al)-481.5(te)19.5(rm)19.6(in)20.7(ol)20.7(og)20.8(y)-490.7(u)0(s)21(e)0(d)]TJ
T*
[(ac)18.5(ro)20.9(ss)-358.9(th)20.7(em)-361.7(va)19.7(ri)20.7(es)19.9(.)-366.3(T)0(h)19.6(u)0(s)15.3(,)-366.3(a)-365.1(b)0(r)15.1(o)0(a)19.7(d)-364(in)20.7(it)14.8(ia)19.5(l)-364.1(k)0(e)13.9(y)0(w)20(o)0(r)20.9(d)0(-)20.9(b)0(a)19.7(s)0(e)14.1(d)-364(li)20.6(t-)]TJ
T*
[(er)19.7(at)19.5(ur)20.9(e)-336.3(s)0(e)14.1(a)0(r)19.7(c)0(h)-325.9(\()0(e)19.7(.)0(g)18.5(.)13.9(,)-337.5()62.3(w)14.2(ho)20.8(le)-326(sy)21(st)20.9(em)18.5(s)-340.7(r)0(e)19.7(s)0(e)19.9(a)0(r)19.7(c)0(h)19.7(,)0()70.4()-335.1()56.5()0(c)19.7(o)0(m)19.6(p)0(l)20.7(e)0(x)19.7(,)0()70.4()]TJ
0 -1.1174 TD
[()62.3()0(i)20.7(n)0(d)15.1(i)0(v)20.7(i)0(d)20.7(u)0(a)19.7(l)0(i)20.6(z)0(e)18.5(d)0(,)18.5()56.5()-387()56.5(c)19.7(om)19.6(pl)20.7(em)18.5(en)19.7(ta)19.6(ry)-382.3(me)18.4(di)20.7(ci)19.5(ne)19.7(,)70.4()-392.7(a)0(n)19.7(d)-392.8()62.3()0(m)19.7(o)0(d)20.8(e)0(l)]TJ
0 -1.1116 TD
[(va)19.7(li)20.6(di)20.7(ty)14.9()62.3()0(\))-514.7(h)0(e)19.7(l)0(p)20.7(e)0(d)-510.2(t)0(o)-514.9(l)0(o)20.7(c)0(a)18.5(t)0(e)-516.1(m)0(a)18.4(n)0(y)-509.1(r)0(e)19.7(l)0(e)13.8(v)0(a)19.7(n)0(t)]TJ
/F15 1 Tf
18.1776 0 TD
[(me)18.8(th)14.9(od)20.8(ol)20.7(og)20.8(ic)19.6(al)]TJ
/F6 1 Tf
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[(pu)20.8(bl)20.7(ic)19.5(at)19.6(io)15(ns)21(,)-418.1(b)0(u)20.8(t)-415.9(pr)15.1(ov)20.8(ed)-406.5(in)20.7(su)15.3(f)21(ci)19.5(en)19.7(t)-421.7(t)0(o)-405.5(i)0(d)20.7(e)0(n)13.9(t)0(i)20.6(f)0(y)-405.3(a)-422.7(re)19.7(pr)20.9(es)19.9(en)19.7(-)]TJ
0 -1.1174 TD
[(ta)19.6(ti)20.6(ve)-251(se)19.9(t)-266.2(o)0(f)]TJ
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1.0137 -1.1174 TD
0 Tc
[(Study)-316.5(selection)-318.9(\(i.e.,)-314.4(identication,)-321.2(charting,)-320.1(and)-315.5(culling\))]TJ
-1.0137 -1.1116 TD
[(continued)-553.9(iteratively)-557.6(until:)-554.3(\(1\))-556.2()50.8(theoretical)-559.7(saturation)48.8()]TJ
7.3823 0 0 6.5614 293.7259 455.5274 Tm
(62)Tj
9.843 0 0 9.843 62.022 440.2204 Tm
[(was)-408.3(reached,)-407.4(in)-405.5(that)-409(review)-407.3(of)-405.3(additional)-405.5(candidate)-412.2(publi-)]TJ
T*
[(cations)-344.2(failed)-337.5(to)-342.1(reveal)-344.3(new)-339.4(WSR)-340.5(methodological)-343.2(features;)]TJ
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T*
[(in)20.7(cl)19.5(ud)15.1(ed)-337.4(st)20.9(ud)20.8(ie)19.6(s)-352.2(h)0(a)19.7(d)-346.7(be)19.7(en)-337.4(di)14.9(re)19.7(ct)19.5(ly)-336.4(re)19.7(co)13.9(m)15(m)0(e)18.4(n)0(d)15.1(e)0(d)-337.4(b)0(y)-336.3(a)0(t)-337.6(l)0(e)13.8(a)0(s)19.9(t)]TJ
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[(on)20.8(e)-313.3(W)0(S)18.7(R)-313.1(ex)19.7(pe)19.7(rt)-301.8(\(i)20.7(nc)13.9(lu)20.7(di)20.7(ng)-301.7(co)19.7(au)19.7(th)20.7(or)15.1(s)-311.9(J)0(.)18.7(R)0(.)-299.3(a)0(n)19.7(d)-312.1(C.)17.5(E.)23.1(\);)-301.8(th)15(e)-313.3(r)0(e)19.7(-)]TJ
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T*
[(pr)20.9(im)19.5(ar)14(y)-231.5(a)0(u)19.7(t)0(h)20.7(o)0(r)-221(\()0(N)14.2(.)13.9(I.)18.5(\).)-223.4(Fo)21(ur)-221(ex)13.9(pe)19.7(rt)20.7(-r)20.9(ec)18.5(om)19.6(me)18.4(nd)15.1(ed)-222.2(st)20.9(ud)20.8(ie)19.5(s)-237(w)0(e)18.8(r)0(e)]TJ
T*
[(ex)19.7(cl)19.5(ud)15.1(ed)-337.4(be)19.7(ca)18.5(us)21(e)-347.8(t)0(h)20.7(e)0(y)19.7(:)-346.8(\(1)20.9(\))-346.6(d)0(i)14.9(d)-340.9(no)15.1(t)-346.8(m)15(ee)12.8(t)-341(t)0(h)15(e)-347.8(st)20.9(ud)20.8(y)-346.7(i)0(n)20.7(c)0(l)19.5(u)0(s)15.3(i)0(o)20.7(n)]TJ
0 -1.1174 TD
[(cr)19.7(it)20.6(er)14(ia)-360.6(\()]TJ
/F15 1 Tf
3.4789 0 TD
(n)Tj
/F9 1 Tf
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(=)Tj
/F6 1 Tf
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[(1\))-365(or)-359.3(\(2)20.9(\))-375.4(w)0(e)18.8(r)0(e)-360.4(m)0(e)18.4(t)0(h)20.7(o)0(d)20.8(o)0(l)14.9(o)0(g)20.8(i)0(c)19.6(a)0(l)19.5(l)0(y)-359.4(v)0(e)13.9(r)0(y)-359.3(s)0(i)20.9(m)0(i)19.5(l)0(a)19.6(r)-375.4(to)]TJ
-4.8439 -1.1116 TD
[(ot)20.7(he)19.7(r)-565.5(s)0(e)19.9(l)0(e)19.6(c)0(t)19.5(e)0(d)-550.5(e)0(x)13.9(e)0(m)18.5(p)0(l)20.7(a)0(r)19.7(s)0(,)-551.5(p)0(r)20.9(o)0(v)20.8(i)0(d)15(i)0(n)20.7(g)-559.8(li)20.6(tt)20.6(le)-556.4(ad)19.7(de)19.7(d)-559.8(v)0(a)19.7(l)0(u)20.7(e)-566.7(to)]TJ
T*
[(th)20.7(e)-336.3(r)0(e)19.7(v)0(i)15(e)0(w)-321(\()]TJ
/F15 1 Tf
4.8842 0 TD
(n)Tj
/F9 1 Tf
.6566 0 TD
(=)Tj
/F6 1 Tf
.7084 0 TD
[(3\))20.9(.)-331.7(T)0(h)19.6(e)-336.3(n)15.2(al)-326(se)19.9(le)19.6(ct)19.5(io)20.7(n)-335.2(o)0(f)-324.7(s)0(t)20.9(u)0(d)15.1(i)0(e)19.6(s)-335(de)19.7(li)20.6(be)19.7(ra)19.7(te)13.8(ly)]TJ
-6.2493 -1.1174 TD
[(ov)20.8(er)19.7(-r)15.1(ep)19.7(re)19.7(se)19.9(nt)15(s)]TJ
/F15 1 Tf
6.6813 0 TD
[(tr)15.1(ad)20.8(it)20.6(io)20.7(na)15.1(l)]TJ
/F6 1 Tf
4.8382 0 TD
[(\(i)15(.)13.9(e)0(.)17.3(,)-648.5(Ay)20(ur)20.9(ve)19.7(di)20.7(c)-647.3(a)0(n)19.7(d)-646.2(Ch)19.8(in)20.7(es)14.1(e\))]TJ
-11.5194 -1.1116 TD
[(me)18.4(di)20.7(ci)19.5(ne)-170.4(sy)21(st)15.1(em)24.2(s,)-171.4(to)-163.6(th)15(or)20.9(ou)20.8(gh)20.8(ly)-169.4(ad)19.7(dr)20.9(es)19.9(s)-179.5(t)0(h)20.7(e)-180.8(pa)19.7(ra)19.7(di)20.7(gm)19.6(-s)21.1(pe)13.9(ci)19.5(c)]TJ
T*
[(di)20.7(ag)19.7(no)15.1(st)20.9(ic)19.5(,)-395.1(i)0(n)20.7(t)0(e)19.6(r)0(v)15.1(e)0(n)19.7(t)0(i)20.6(o)0(n)20.8(,)-395.1(an)19.7(d)-398.5(o)0(u)20.8(t)0(c)19.6(o)0(m)19.6(e)-393.9(de)13.9(si)20.9(gn)-382.3(co)13.9(ns)21(id)20.7(er)19.7(at)19.5(io)15(ns)]TJ
0 -1.1174 TD
[(th)20.7(at)-245.4(ar)19.7(is)20.9(e)-249.9(i)0(n)-244.2(t)0(h)20.7(e)0(s)19.9(e)-249.9(co)19.7(nt)15(ex)19.7(ts)20.9(.)]TJ
/F14 1 Tf
8.9663 0 0 8.9663 62.022 220.9889 Tm
[(Data)-337.7(charting)]TJ
/F6 1 Tf
9.843 0 0 9.843 72 204.548 Tm
[(Focused)-280.4(around)-272.7(three)-278.6(primary)-280.9(analytic)-283.4(categoriesStudy)]TJ
-1.0137 -1.1116 TD
[(Design,)-369.1(Intervention)-373(Selection,)-368.4(and)-367.3(Outcome)-369.4(Evaluation)]TJ
0 -1.1174 TD
[(the)-436.6(primary)-436.4(author)-439.8(\(N.I.\))-438.3(summarized)-437.3(and)-442.2(evaluated)-435.3(each)]TJ
0 -1.1116 TD
[(candidate)-343.1(study)-333.7(using)-339.5(an)-337.4(emergent)-341.9(set)-338.5(of)-336.2(tables)-337.3(and)-338.5(charts.)]TJ
T*
[(Through)-538.8(a)-537.9(constant)-535.3(comparative)-542.4(approach)-542.2(that)-535.7(reviewed)]TJ
T*
[(each)-359.2(study)-351(in)-353.7(relation)-357.1(to)-353.7(all)-350.3(others,)]TJ
7.3823 0 0 6.5614 204.4913 154.148 Tm
(63)Tj
9.843 0 0 9.843 215.3763 149.7826 Tm
[(a)-353.6(set)-350(of)-353.5(analytic)-358.3(sub-)]TJ
-15.58 -1.1174 TD
[(parameters)-454.5(and)-453.7(conceptual)-453.7(frames)-453.4(progressively)-454.2(emerged.)]TJ
0 -1.1116 TD
[(This)-518.1(process)-516.5(permitted)-514.9(a)-514.9(nalized)-519.3(study)-512.3(selection)-520.5(and)-517.1(a)]TJ
T*
[(detailing)-358.3(of)-359.3(each)-359.2(studys)-358.8(distinct)-361.6(and)-355.8(nondistinct)-359.2(methodo-)]TJ
0 -1.1174 TD
[(logical)-338.7(features.)]TJ
/F14 1 Tf
8.9663 0 0 8.9663 62.022 83.9622 Tm
[(Expert)-334.4(validation)-338.5(of)-330.4(ndings)]TJ
/F6 1 Tf
9.843 0 0 9.843 72 67.5212 Tm
[(While)-389.3(analysis)-391.1(and)-384.6(reporting)-391.4(were)-387.7(undertaken)-389(primarily)]TJ
-1.0137 -1.1116 TD
[(by)-497.5(the)-499.9(primary)-499.7(author)-503.2(\(N.I.\),)-499.3(a)-497.6(subset)-502.8(of)-497.5(categorizations)]TJ
25.504 67.9242 TD
[(related)-512.5(to)-509.2()50.8(dual)-513.6(diagnostics)47.8()-507.9(and)-505.6(paradigm-specic)-519.9(out-)]TJ
0 -1.1174 TD
[(come)-8(s)-306.2(was)-304.6(independen)-8.9(tly)-303.1(corroborated)-316.2(by)-301.7(another)-309.6(coauthor)]TJ
0 -1.1116 TD
[(\()-127.8(J.R.\).)-342.7(All)-338.5(coauthors)-340.5(\()-127.8(J.R.,)-341.6(C.E.,)-337.3(J.W.\))-340.5(contributed)-343.1(insights)]TJ
T*
[(as)-550.3(to)-549.5(the)-546(emerging)-548.1(conceptual)-551.6(categories)-551.4(as)-550.3(the)-546(project)]TJ
T*
[(progressed)-370(and)-367.3(provided)-367.2(input)-362.9(on)-365.1(the)-367.5(nal)-362.6(analyses)-369.1(before)]TJ
0 -1.1174 TD
[(this)-338.5(works)-335.5(peer)-335(review)-332.4(by)-336.3(other)-335.1(WSR)-334.7(eld)-333.8(experts.)]TJ
/F14 1 Tf
8.9663 0 0 8.9663 313.0582 645.6754 Tm
[(Result)-340.5(collation,)-331.3(summary,)-332.9(and)-335.7(reporting)]TJ
/F6 1 Tf
9.843 0 0 9.843 323.0361 629.2345 Tm
[(Results)-303.5(are)-305.1(synthetically)-306.2(presented)-307.1(and)-304(discussed)-305.5(in)-301.8(what)]TJ
-1.0137 -1.1174 TD
[(follows)-509.7(using)-506.5(both)-505.6(narrative)-508.9(and)-511.3(graphical)-509(reporting.)-504.3(To)]TJ
0 -1.1116 TD
[(facilitate)-528.9(reading)-517(ease,)-523.7(in-text)-521.8(WSR)-519.1(exemplar)-526.2(references)]TJ
T*
[(name)-376.6(rst)-372.8(authors)-377.4(only;)-374.4(full)-373.2(citations)-375.4(may)-374.3(be)-372(found)-374.1(in)-376.7(the)]TJ
0 -1.1174 TD
[(reference)-326.7(list.)-319.1(To)-320.2(provide)-320(context)-321.3(and)-321.2(language)-323.5(to)-319.1(facilitate)]TJ
0 -1.1116 TD
[(nuanc)-7.8(ed)-423.8(reporting)-420.2(of)-428.4(the)-419.3(WSR)-426.9(elds)-428(features,)-424.5(two)-424.8(novel)]TJ
T*
[(theoretical)-339.8(frameworks)-337.7(are)-339.7(presented)-335.8(below.)]TJ
/F4 1 Tf
8.9663 0 0 8.9663 313.0582 538.7526 Tm
(Theory)Tj
/F14 1 Tf
0 -1.8336 TD
[(Model)-334.3(validity)-337.4(framework)]TJ
/F6 1 Tf
9.843 0 0 9.843 323.0361 505.8707 Tm
[(The)-357(model)-353.6(validity)-350.3(principle)-358.2(has)-355.6(been)-352.3(conceptualized)-356.9(as)]TJ
-1.0137 -1.1116 TD
[(central)-397.3(to)-388.2(WSR;)-393.6(and,)-388(as)-394.8(noted)-392.7(earlier)-391.5(on,)-391.5(various)-388.9(scholars)]TJ
T*
[(have)-271.7(suggested)-271.2(ways)-265.4(in)-267.3(which)-266.9(this)-269.4(principle)-266(may)-270.6(be)-262.6(enacted)]TJ
0 -1.1174 TD
[(within)-290.1(clinical)-289.3(research)-283.9(contexts.)-291.1(What)-284.4(remained)-290.1(implicit)-282.6(in)]TJ
0 -1.1116 TD
[(much)-392.7(\(although)-391.4(not)-383.6(all\))-391.7(of)-388.1(the)-390.5(early)-388.1(WSR)-392.3(methodological)]TJ
T*
[(literature)-279.9(is)-272.8(that)-276.5(WSR)-271.4(itself)-278.6(may)-270.6(be)-274.1(understood)-277(as)-273.9(part)-270.6(of)-272.9(an)]TJ
0 -1.1174 TD
[()45(integrative)-293.6(medicine)48.5()-289(movement)]TJ
7.3823 0 0 6.5614 451.2755 444.529 Tm
(64)Tj
9.843 0 0 9.843 461.4802 440.107 Tm
[(geare)-9(d)-283.3(t)0(o)-290.3(transforming)]TJ
-15.0789 -1.1116 TD
[(dominant)-253.4(health)-251.1(care)-255.5(systems)-251.6(such)-253(that)-253.5(TCIM)-249.4(therapies)-255.3(may)]TJ
T*
[(be)-446.9(more)-444.5(broadly)-446.7(integrated)-452.6(alongside)-444.3(or)-445.7(as)-446.7(an)-441.1(adjunct)-448(to)]TJ
T*
[(conve)-7.8(ntional)-470(biomedical)-471.1(care.)-472.1(Clinical)-473.5(research)-474(is)-468.7(in)-468.9(this)]TJ
0 -1.1174 TD
[(scenario)-415.4(envisi)-7.8(oned)-408.7(as)-412.1(a)-411.2(necessary)-417.3(but)-412.4(insufcient)-417.6(tool)-407.8(to)]TJ
0 -1.1116 TD
[(help)-339.8(to)-330.6(dismantle)-336.2(barriers)-339.3(to)-330.6(integration.)]TJ
7.3823 0 0 6.5614 475.8235 389.707 Tm
(17)Tj
9.843 0 0 9.843 323.0361 374.3999 Tm
[(Several)-725.3(scholars,)-728.5(critiquing)-721.1(the)-724.6(integrative)-730.3(medicine)]TJ
-1.0137 -1.1174 TD
[(project,)-336.2(have)-329.3(however)-333.4(suggested)-334.5(a)-330.6(potential)-329.5(for)-331.5(the)-327.1(distinct)]TJ
0 -1.1116 TD
[(paradigmat)-10.2(ic)-354.8(features)-357.8(of)-353.5(and)-355.8(practices)-354.4(with)-356.9(origins)-359.1(in)-353.7(non-)]TJ
T*
[(biomedical)-690(therapeutic)-685.3(systems)-683.5(to)-676.2(be)-683(co-opted,)-682.8(appro-)]TJ
0 -1.1174 TD
[(priated,)-365(or)-365(assimilated)-368.3(in)-359.4(such)-362.5(a)-365.1(process.)]TJ
7.3823 0 0 6.5614 479.2251 334.9417 Tm
(65)Tj
9.843 0 0 9.843 490.1668 330.5196 Tm
[(Model)-364.8(validity,)]TJ
-17.9933 -1.1116 TD
[(as)-406.3(a)-405.4(theoretical)-408.9(construct,)-407.4(represents)-405.8(a)-405.4(commitment)-409.1(to)-405.5(ac-)]TJ
T*
[(tively)-273.1(preserving)-278.2(these)-272.7(paradigms)-272.6(and)-269.4(practices)-279.5(in)-267.3(their)-277.6(own)]TJ
T*
[(right,)-493(an)-492.9(approach)-490.3(aligned)-494.1(with)-489.3(the)-488.4(concept)-495.1(of)-491.7(a)-486.1(clearly)]TJ
0 -1.1174 TD
[()45(articulated,)46.3()]TJ
7.3823 0 0 6.5614 369.5243 291.0613 Tm
(66)Tj
9.843 0 0 9.843 380.9763 286.696 Tm
[(equitable)-417(medical)-415.9(pluralism,)]TJ
7.3823 0 0 6.5614 496.5731 291.0613 Tm
(67)Tj
9.843 0 0 9.843 508.025 286.696 Tm
[(rather)-417.9(than)]TJ
-19.8076 -1.1116 TD
[(an)-337.4(assimilative)-340.7(mode)-329.3(of)-336.2(integration.)]TJ
7.3823 0 0 6.5614 458.3054 280.1196 Tm
(65)Tj
9.843 0 0 9.843 323.0361 264.8125 Tm
[(What)-480.3(WSR)-473(pioneers)-483.3(were)-474.1(not)-475.7(able)-479.2(to)-474.6(fully)-478(apprise)-476.5(in)]TJ
-1.0137 -1.1174 TD
[(advan)-7.8(ce)-321.3(was)-327.7(how)-326.7(and)-321.2(to)-324.9(what)-329.1(degree)-326.8(future)-324.6(WSR)-323.2(methods)]TJ
0 -1.1116 TD
[(might)-243.2(ultimately)-251.4(align)-243.1(or)-238.3(diverge)-246.3(with)-247.4(conventional)-241.7(research)]TJ
T*
[(strate)-9(gies)-299.2(in)-296.1(pursuit)-301.5(of)-301.7(model)-301.8(validity.)-301.9(To)-297.1(facilitate)-304.3(analysis)]TJ
0 -1.1174 TD
[(of)-307.4(these)-307.3(points)-306.2(in)-307.6(the)-304.1(present)-309.4(scoping)-308.3(review,)-307.1(it)-307.7(is)-301.6(proposed)]TJ
0 -1.1116 TD
[(that)-339.9(the)-332.9(model)-336.3(validity)-338.8(principle)-335.1(be)-337.4(theoretically)-342.1(differenti-)]TJ
T*
[(ate)11.5(d)-329.4(int)13.7(o)-329.4(thr)13.9(ee)-327.1(co-)12.8(emb)11.6(edd)12.8(ed)-325.9(ca)12.8(teg)12.7(ori)13.9(es)-325.7(as)-325.7(see)11.8(n)-329.4(i)0(n)-324.9(Fig)14(ure)-321.2(1:)]TJ
/F15 1 Tf
0 -1.1174 TD
[(par)14.2(adi)13.8(gm)-198.9(co)13.9(mpa)13.1(tib)13.7(ili)13.6(ty)]TJ
/F6 1 Tf
9.2904 0 TD
(,)Tj
/F15 1 Tf
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[(par)14.2(adi)13.8(gm)-193.1(con)12.8(sis)14.2(ten)12.7(cy)]TJ
/F6 1 Tf
8.6165 0 TD
[(,)-199.3(and)]TJ
/F15 1 Tf
2.085 0 TD
[(par)14.2(adi)13.8(gm)]TJ
-20.4412 -1.1116 TD
[(spe)13(ci)12.7(cit)12.6(y.)]TJ
/F6 1 Tf
4.5329 0 TD
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